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Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

Ling Hou,1,&ast; Jinbo Zhao,2,&ast; Ting He,1,&ast; Yinhua Luo,3 Ke Su,2 Yuanhong Li,2 Ruiyang Zhu3 1Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, Hubei Province, People’s Republic of China; 3Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi, 445400, People’s Republic of China, Email lyh0101@vip.163.com Ruiyang Zhu, Center for Gene Diagnosis and Department of Clinical Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China, Email zhuruiyang@whu.edu.cnAbstract: Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis classified as an autoimmune small-vessel vasculitis. Clinically, approximately 80% of affected organs in GPA involve the upper/lower respiratory tract and kidneys, with cardiovascular system involvement being rare. Here, we report a case of a 50-year-old female patient who presented with sudden-onset chest pain lasting for 1 hour. The patient had normal body temperature, and markers of infection such as C-reactive protein and erythrocyte sedimentation rate were within normal limits. Electrocardiography revealed ST-segment elevation in inferior, precordial, and posterior leads. Emergency coronary angiography showed no significant obstructive disease, prompting consideration of vasospastic angina given the patient’s recurrent chest pain symptoms and findings on laboratory and imaging studies. The patient underwent treatment including coronary vasospasm antagonists and immunomodulation, resulting in clinical improvement and subsequent discharge. During a 7-month follow-up period, the patient did not experience any further adverse cardiovascular events.Keywords: granulomatosis with polyangiitis, vasospastic angina, case report

Luyang Zhang,1,&ast; Yuan Luo,1,&ast; Jiewen Long,1 Yan Yin,1 Qin Fu,2 Lei Wang,1 Sandip Patil1 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Nursing, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sandip Patil; Lei Wang, Department of Haematology and Oncology, Shenzhen Children’s Hospital, 7019 Yitian Road, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83008283, Email sandippatil1309@yahoo.com; 405112310@qq.comBackground: Oral mucositis (OM) poses a significant challenge in children undergoing hematopoietic stem cell transplantation (HSCT). There is a gap between clinical practice and the evidence, and nursing practices is not standardized.Objective: This study aims to evaluate the effectiveness of applying the evidence for preventing HSCT chemotherapy-induced OM in children and to elevate the nurses’ compliance to the evidence.Methods: Following the clinical evidence practice application model of the Joanna Briggs Institute (JBI) evidence-Based Care Center. The process included reviewing literature, extracting evidence, identifying gaps, developing audit criteria, conducting a baseline audit, creating an action plan, implementing evidence-based interventions, and assessing outcomes.Results: After the evidence implementation, 6 out of 12 audit criteria with poor compliance are significantly improved, with statistically significant differences (P< 0.05). The incidence of OM decreases, with a statistically significant difference (66.6% vs 36.7%, P=0.02). The incidence of grade I, II, III, and IV OM also decreases (30% vs 23.3%, 23.3% vs 13.4%, 10% vs 0%, and 3.3% vs 0%). Ultimately, the standardized oral care practice routine and workflows to prevent OM were established.Conclusion: Bridging the gap between evidence and clinical practice can standardize nurse behavior, decrease the incidence of OM, and lower the OM severity in children undergoing HSCT.Keywords: children, hematopoietic stem cell transplantation, oral mucositis, evidence-based practice

Wei Xiao,1 Yanqiong Liu,2 Hua Tang,3 Qin Xie,2 Yanlan Luo,2 Tao Mei1 1Department of Neurosurgical Care Unit, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 2Cardiovascular Medicine Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 3Neurosurgery Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of ChinaCorrespondence: Tao Mei, Email yilan1008@sina.comBackground: Intracerebral hemorrhage (ICH) affects up to 1% of chronic oral anticoagulation (OAC) users per year. This study explored the knowledge, attitude and practice (KAP) towards ICH prevention among patients taking OACs.Methods: This multicenter cross-sectional survey was conducted at 4 hospitals from February to May 2023, and a self-administered questionnaire was developed to assess KAP toward ICH prevention among patients taking OACs. Structural equation modeling was used to assess the relationship between KAP.Results: A total of 536 valid questionnaires (67.25%) were analyzed, from 43.8% participants on Warfarin, 40.5% on Rivaroxaban and 15.7% on Dabigatran. The average knowledge, attitudes and practice scores were 9.22, 24.11, and 28.01 out of 16, 35 and 40, respectively. Participants who received Rivaroxaban had lower knowledge scores but higher attitude and practice store compared to those who received Warfarin or Dabigatran (all p < 0.001). According to Structure Equation Modeling, attitude had direct positive effect on practice (β = 0.694 [0.603– 0.804], p = 0.012), while knowledge had direct negative effect on attitude (β = − 2.077 [− 2.507– 1.651], p = 0.013), as well as negative effect on practice, both direct (β = − 0.450[− 0.689– 2.03], p=0.012), and indirect (β = − 1.441 [− 1.928– 1.192], p = 0.004).Conclusion: Patients taking OACs showed insufficient knowledge, negative attitude and proactive practice regarding ICH; practice scores were affected by age, type of anticoagulation medication, and attitude rather than knowledge.Keywords: cerebral hemorrhage, anticoagulants, warfarin, dabigatran, rivaroxaban, knowledge, attitude, practice

Bei Li,1,2,&ast; Yuting Luo,1,2,&ast; Geng Liu,1,2 Maling Gou,3 Lei Feng,1,2 Xiwen Ye,1,2 Jianrong Xu,1,2 Yaotian Fan,1,2 Zhen You1,2 1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen You, Tel/Fax +86 028 85423823, Email youzhen@wchscu.cnIntroduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary.Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice.Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects.Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.Keywords: hepatocellular carcinoma, photothermal therapy, NDI polymer, NIR-II imaging

Yi Zhang,1 Dang Liu,2 Bin Qiao,3 Yuanli Luo,3 Liang Zhang,3 Yang Cao,3 Haitao Ran,3,&ast; Chao Yang4,&ast; 1Department of Ultrasound, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Ran, Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 13512373563, Email ranhaitao@cqmu.edu.cn Chao Yang, Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China, Tel +86 13883095836, Email ychaof737@163.comPurpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.Keywords: Bi-DTPA, IR780, radiotherapy, tumor microenvironment hypoxia, photothermal therapy

YiLin Luo, Xin Yue Bai, Lei Zhang, Qian Qian Hu, Ning Zhang, Jun Zhi Cheng, Ming Zheng Hou, Xiao Long Liu Yan ‘an Small Molecule Innovative Drug R&D Engineering Research Center, School of Medicine, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Xiao Long Liu, Email liuxiaolong@yau.edu.cnAbstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.Keywords: ferroptosis inducers, small molecules, PROTACs, PDT, SDT, nanomaterials

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Xichen Wan,1– 3 Tong Lin,1– 3 Yunzhen Luo,4 Jiaxu Hong,1– 3,5 Jingyi Cheng,1– 3,&ast; Keqing Zhao6,&ast; 1Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 2NHC Key Laboratory of Myopia and Related Eye Diseases, Shanghai, People’s Republic of China; 3Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Zhao, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email rhinoresearch@163.com Jingyi Cheng, Department of Ophthalmology and Visual Science, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email tippicjy@126.comPurpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis.Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer’s tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition.Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P> 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001).Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.Keywords: vidian neurectomy, ocular surface, dry eye

Peng Ge,1– 3,&ast; Yalan Luo,3,&ast; Jinquan Zhang,1– 3,&ast; Jie Liu,1– 3 Caiming Xu,1,4 Haoya Guo,1– 3 Aixia Gong,3 Guixin Zhang,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 4Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Comprehensive Cancer Center, Duarte, CA, USA&ast;These authors contributed equally to this workCorrespondence: Guixin Zhang; Hailong Chen, Email zgx0109@126.com; chenhailong@dmu.edu.cnBackground: Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive.Methods: This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate.Results: MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway.Conclusion: By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use. Keywords: acute pancreatitis, qingyi granule, dexamethasone, acute lung injury, clinical efficacy, Mendelian randomization, rat

Jianing Tang,1,2,&ast; Yuexin Luo,1,2,&ast; Qirui Wang,1,2 Juntao Wu,1,2 Yulong Wei1 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2First Clinic School, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulong Wei, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, People’s Republic of China, Email yulongwei_HUST@163.comAbstract: As a major cause of low back pain, intervertebral disc degeneration is an increasingly prevalent chronic disease worldwide that leads to huge annual financial losses. The intervertebral disc consists of the inner nucleus pulposus, outer annulus fibrosus, and sandwiched cartilage endplates. All these factors collectively participate in maintaining the structure and physiological functions of the disc. During the unavoidable degeneration stage, the degenerated discs are surrounded by a harsh microenvironment characterized by acidic, oxidative, inflammatory, and chaotic cytokine expression. Loss of stem cell markers, imbalance of the extracellular matrix, increase in inflammation, sensory hyperinnervation, and vascularization have been considered as the reasons for the progression of intervertebral disc degeneration. The current treatment approaches include conservative therapy and surgery, both of which have drawbacks. Novel stimuli-responsive delivery systems are more promising future therapeutic options than traditional treatments. By combining bioactive agents with specially designed hydrogels, scaffolds, microspheres, and nanoparticles, novel stimuli-responsive delivery systems can realize the targeted and sustained release of drugs, which can both reduce systematic adverse effects and maximize therapeutic efficacy. Trigger factors are categorized into internal (pH, reactive oxygen species, enzymes, etc.) and external stimuli (photo, ultrasound, magnetic, etc.) based on their intrinsic properties. This review systematically summarizes novel stimuli-responsive delivery systems for intervertebral disc degeneration, shedding new light on intervertebral disc therapy.Keywords: stimulus response, delivery system, intervertebral disc degeneration, biomaterial

Hui Rao,1 Xianfang Wang,2 Yu Luo,3 Liu Liang,1 Wei Ye,1 Xuemin Guo1 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gynaecology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Xuemin Guo, Department of Laboratory Medicine, Meizhou People’s Hospital, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email Guoxm12@126.comBackground: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤ 55 years old in men and ≤ 65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study.Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk.Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130– 5.569, p=0.024), overweight (BMI≥ 24.0 vs 18.5– 23.9: OR 5.047, 95% CI: 3.275– 7.777, p< 0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595– 4.961, p< 0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397– 3.437, p=0.001) were the independent risk factors of early onset CAS.Conclusion: In men ≤ 55 years old and women ≤ 65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥ 24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.Keywords: aldehyde dehydrogenase 2, gene polymorphism, coronary artery stenosis, early onset

Lian Weng,1– 3,&ast; Xiongjunjie Luo,1– 3,&ast; Yuxi Luo,1– 3 Qian Zhang,1– 3 Kaitao Yao,1– 3 Junjie Tan,1– 3 Yiran Yin1– 3 1Department of orthopedics, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Sichuan Provincial Laboratory of Orthopedic Engineering, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiran Yin, Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, No. 25 Tai Ping Street, Jiang Yang District, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel +13982457750, Email yiranyin@swmu.edu.cnBackground: Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases.Methods: In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells.Results: Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases.Conclusion: This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.Keywords: sleep apnea syndrome, osteoarthritis, Mendelian randomization, bioinformatics

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

Yinan Cao,1– 3,&ast; Fan Li,1– 3,&ast; Zhenxuan Sun,1– 3 Jin Liu,1– 3 Jie Liu,1– 3 Qi Yang,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Luo; Hailong Chen, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, 116011, Liaoning, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email luoyalanxueshu@163.com; chenhailong@dmu.edu.cnPurpose: Explore the therapeutic effects and regulatory mechanism of Qingyi Decoction (QYD) on severe acute pancreatitis (SAP) associated acute lung injury (ALI).Methods: We identified the constituents absorbed into the blood of QYD based on a network pharmacological strategy. The differentially expressed genes from the GEO database were screened to identify the critical targets of QYD treatment of SAP-ALI. The SAP-ALI rat model was constructed.Some methods were used to evaluate the efficacy and mechanism of QYD in treating SAP-ALI. LPS-stimulated pulmonary microvascular endothelial cell injury simulated the SAP-induced pulmonary endothelial injury model. We further observed the therapeutic effect of QYD and CDK5 plasmid transfection on endothelial cell injury.Results: 18 constituents were absorbed into the blood, and 764 targets were identified from QYD, 25 of which were considered core targets for treating SAP-ALI. CDK5 was identified as the most critical gene. The results of differential expression analysis showed that the mRNA expression level of CDK5 in the blood of SAP patients was significantly up-regulated compared with that of healthy people. Animal experiments have demonstrated that QYD can alleviate pancreatic and lung injury inflammatory response and reduce the upregulation of CDK5 in lung tissue. QYD or CDK5 inhibitors could decrease the expression of NFAT5 and GEF-H1, and increase the expression of ACE-tub in SAP rat lung tissue. Cell experiments proved that QYD could inhibit the expression of TNF-α and IL-6 induced by LPS. Immunofluorescence results suggested that QYD could alleviate the cytoskeleton damage of endothelial cells, and the mechanism might be related to the inhibition of CDK5-mediated activation of NFAT5, GEF-H1, and ACE-tub.Conclusion: CDK5 has been identified as a critical target for pulmonary endothelial injury of SAP-ALI. QYD may partially alleviate microtubule disassembly by targeting the CDK5/NFAT5/GEF-H1 signaling pathway, thus relieving SAP-induced pulmonary microvascular endothelial cell injury. Keywords: Qingyi decoction, severe acute pancreatitis, acute lung injury, CDK5, microtubule

Fan Li,1– 3,&ast; Zhengjian Wang,4,&ast; Yinan Cao,1– 3 Boliang Pei,1– 3 Xinyu Luo,1– 3 Jin Liu,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Shurong Ma,1,3 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shurong Ma; Hailong Chen, Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, Liaoning, 116011, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email shurongma94@163.com; chenhailong@dmu.edu.cnAbstract: The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.Keywords: severe acute pancreatitis-associated acute lung injury, intestinal mucosal immune barrier, gut microbiota, gut-lung axis, migration of immune cells

Lujie Wei,1,&ast; Pingyang Li,2,&ast; Xiaofeng Liu,1 Yuxia Wang,1 Zhengping Tang,1 Hang Zhao,1 Lu Yu,3 Kaixiu Li,1 Jianping Li,1 Min Du,4 Xinzhu Chen,2 Xin Zheng,2 Yixiong Zheng,5 Yao Luo,2 Jing Chen,5 Xiamin Jiang,6 Xiaobing Chen,7 Huaicong Long1 1Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Medical College, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Nanbu County People’s Hospital, Nanbu, Sichuan, People’s Republic of China; 5College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 6Clinical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaicong Long, Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18981838105, Fax +86-28-8779 5585, Email longhc69@163.comBackground: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear.Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year.Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC).Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%).Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.Keywords: chronic obstructive pulmonary disease, frailty, acute exacerbations

Zhongxiang Liu,1,&ast; Shuhua Han,2,&ast; Yuhong Luo,3,&ast; Zhangyan Zhao,4 Lingyu Ni,5 Linlin Chai,6 Haicheng Tang4 1Department of Pulmonary and Critical Care Medicine, the Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, the First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 3College of Life Science and Technology, Guangxi University, Nanning, 530004, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China; 5China School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210046, People’s Republic of China; 6Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, The First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Chai, Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China, Email chailinlin0924@163.com Haicheng Tang, Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901, Caolang Road, Jinshan District, Shanghai, 201508, People’s Republic of China, Email thc822@163.comBackground: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored.Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP.Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis.Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.Keywords: PERP, lung adenocarcinoma, apoptosis, prognosis

Yixue Hu,1 Dongna Wang,2 Tianyu Zhang,2 Meng Lei,3 Yingnan Luo,2 Zhimeng Chen,3 Yuting Li,2 Dandan Duan,2 Liefeng Zhang,1 Yongqiang Zhu1,2 1College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 2School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 3College of Science, Nanjing Forestry University, Nanjing, People’s Republic of ChinaCorrespondence: Liefeng Zhang; Yongqiang Zhu, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.Methods: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.Results: Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy.Conclusion: Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC. Keywords: photodynamic therapy, gene therapy, hypoxia, invasion, mitochondrial target, triple-negative breast cancer

Chunlan Fu,1 Yuanyuan Zhu,2 Weijia Huang,2 Yi Luo,2 Yongxian Hu,2 He Huang,2 Jie Sun2 1Department of Hematology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, Zhejiang, 311800, People’s Republic of China; 2Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, People’s Republic of ChinaCorrespondence: Jie Sun; He Huang, Email jsun1492@zju.edu.cn; huanghe@zju.edu.cnBackground: Patients with hematologic malignancies usually have severe immunodeficiency and are much more likely to be severe after COVID-19 infection. Tocilizumab is a monoclonal antibody of interleukin-6 (IL-6) and is recommended for treating severe conditions in the latest COVID-19 treatment guidelines. However, the efficacy and safety of tocilizumab in hematologic malignancy patients have yet to be clarified. We report five hematologic malignancy patients with severe COVID-19 infection who were all successfully recovered with tocilizumab treatment.Methods: We reported five hematologic malignant patients who developed severe COVID-19 infection and received tocilizumab at the First Affiliated Hospital of Zhejiang University School of Medicine during the COVID-19 pandemic in China from Dec 2022 to Mar 2023. We observed the effect of tocilizumab on COVID-19 infection and evaluated its safety.Results: Five hematologic malignancy patients with severe COVID-19 infection were retrospectively enrolled. The dosage of tocilizumab was 400– 480mg once; one patient used a second dose of tocilizumab on the third day of medication. After receiving tocilizumab treatment, all five patients experienced a rapid decrease in body temperature and C-reactive protein (CRP) within 24 hours and improved oxygen requirement within one to three days (one patient did not experience hypoxia). Chest CT scans after one week showed absorption of lung infection. The serum IL-6 levels of three patients showed an initial increase followed by a decrease. None of the patients experienced grade 3– 4 hematologic or non-hematologic toxicity.Conclusion: Tocilizumab can improve the outcome of severe COVID-19 infection in hematologic malignancy patients with severe immunodeficiency without severe adverse reactions.Keywords: COVID-19, hematologic malignancy, tocilizumab

Yu Luo,1,2 Ru Pan,1,2 Hui Rao,2,3 Xing Chen,4 Haikun Yang1,2 1Department of Gynaecology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Major Genetic Disorders, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Data Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Haikun Yang, Department of Gynaecology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Add: No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email 13923023911@139.comObjective: To investigate the relationship between BRCA1/2 gene mutation and clinicopathological features in ovarian cancer patients, so as to develop precise individualized treatment plan for patients.Methods: Patients diagnosed with ovarian cancer between January 2018 and July 2023 who underwent BRCA1/2 genetic testing were retrospectively analyzed. The clinicopathological characteristics (age, body mass index (BMI), family history of ovarian cancer, pregnancy history, menopause status, tumor size, histopathology, Federation of Gynecology and Obstetrics (FIGO) staging, and ascites) of non-carriers and BRCA1/2 variant carriers were compared. Logistic regression analysis was used to explore the relationship between BRCA1/2 variants and clinicopathological characteristics of ovarian cancer.Results: A total of 284 ovarian cancer patients were collected, and the subjects were divided into two groups, 197 non-carriers and 87 BRCA1/2 variants carriers. The proportion of serous ovarian carcinoma in BRCA1/2 variant carriers is higher than that in non-BRCA variant carriers (78.2% vs 60.9%, p=0.015). There were 51 patients with BRCA pathogenic or likely pathogenic variant, 22 patients with BRCA likely benign variant, and 14 patients with BRCA variants of uncertain significance (VUS). The proportion of serous ovarian carcinoma in patients with BRCA pathogenic/likely pathogenic variant is higher than that in patients with BRCA likely benign variant and BRCA VUS (94.1% vs 50.0% and 64.3%. p< 0.001). There were no statistically significant differences in BMI, family history of ovarian cancer, pregnancy history, menopause status, maximum diameter of the tumor lesion, FIGO stage, and ascites among patients with different grades of variants. Multivariate logistic regression analysis showed that serous ovarian carcinoma was related to BRCA mutation (Serous carcinoma vs non-serous carcinoma: OR 2.145, 95% CI: 1.044– 4.407) (p=0.038).Conclusion: Patients with BRCA1 variant develop ovarian cancer at a younger age than those with the BRCA2 variant. The proportion of FIGO stage III–IV in patients with BRCA pathogenic + likely pathogenic variant was significantly higher than those in patients with other variants. Germline BRCA1/2 variants were most frequently identified in serous ovarian carcinoma patients.Keywords: ovarian cancer, BRCA1, BRCA2, clinicopathological characteristics

Hongcai Yang,&ast; Tianhao Cong,&ast; Yingen Luo, Chao Yang, Jinrui Ren, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comObjective: To investigated the association between sarcopenia and the prognosis and adverse events of hepatocellular carcinoma (HCC) patients undergoing interventional therapy combined with immunotherapy and targeted therapy.Methods: Between January 2019 and December 2022, patients with unresectable HCC who received interventional therapy combined with immunotherapy and targeted therapy were included in this study. Total skeletal muscle area at the L3 level was normalized for height in m2 as the skeletal muscle index (SMI). All patients were divided into low and high SMI group according to the median SMI.Results: Ninety-six consecutive patients were included eventually, with 49 patients in the high-SMI group and 47 patients in the low-SMI group. In the low-SMI group, the median overall survival (OS) was 459.00 days (95% CI, 334.76– 583.24 days), and the 3-, 6-, and 12-month OS rates were 100%, 89.4% and 68.1%, respectively. In the high-SMI group, the median OS was not reached, and the 3-, 6-, and 12-month OS rates were 100%, 98% and 79.5%, respectively (p< 0.05). SMI and Barcelona Clinic Liver Cancer (BCLC) C stage were independent prognostic factors for OS (p< 0.05). In the low-SMI group, 26 patients had treatment-related adverse events (TRAEs), resulting in dose adjustment or treatment suspension for 10 patients. In the high-SMI group, 33 patients had TRAEs, and 18 patients received dose adjustment or treatment suspension; the between-group difference was nonsignificant (p> 0.05).Conclusion: SMI is associated with the prognosis of HCC patients receiving interventional therapy combined with immunotherapy and targeted therapy, and sarcopenia is an independent risk factor for OS. However, sarcopenia does not seem to predict the occurrence of adverse events.Keywords: hepatocellular carcinoma, sarcopenia, immune checkpoint inhibitors, tyrosine kinase inhibitors, transarterial chemoembolization

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population

Jiaxin Zeng,1,&ast; Chen Zhou,2,&ast; Qun Yi,1,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Huiguo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Jiarui Zhang,1 Lige Peng,1 Jiaqi Pu,1 Haixia Zhou1 On behalf of the MAGNET AECOPD Registry Investigators1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Center of Infectious Diseases, Division of Infectious Diseases in State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiu jiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cnBackground: The Rome severity classification is an objective assessment tool for the severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on readily measurable variables but has not been widely validated. The aim of this study is to evaluate the validity of the Rome classification in distinguishing the severity of AECOPD based on short-term mortality and other adverse outcomes.Methods: The Rome severity classification was applied to a large multicenter cohort of inpatients with AECOPD. Differences in clinical features, in-hospital and 60-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) and invasive mechanical ventilation (IMV) usage were compared among the mild, moderate and severe AECOPD according to the Rome proposal. Moreover, univariate logistic analysis and Kaplan Meier survival analysis were also performed to find the association between the Rome severity classification and those adverse outcomes.Results: A total of 7712 patients hospitalized for AECOPD were included and classified into mild (41.88%), moderate (40.33%), or severe (17.79%) group according to the Rome proposal. The rate of ICU admission (6.4% vs 12.0% vs 14.9%, P < 0.001), MV (11.7% vs 33.7% vs 45.3%, P < 0.001) and IMV (1.4% vs 6.8% vs 8.9%, P < 0.001) increased significantly with the increase of severity classification from mild to moderate to severe AECOPD. The 60-day mortality was higher in the moderate or severe group than in the mild group (3.5% vs 1.9%, 4.3% vs 1.9%, respectively, P < 0.05) but showed no difference between the moderate and severe groups (2.6% vs 2.5%, P > 0.05), results for in-hospital mortality showed the same trends. Similar findings were observed by univariate logistic analysis and survival analysis.Conclusion: Rome severity classification demonstrated excellent performance in predicting ICU admission and the need for MV or IMV, but how it performs in differentiating short-term mortality still needs to be confirmed.Keywords: AECOPD, the Rome severity classification, short-term mortality, intensive care unit admission, mechanical ventilation, multicenter cohort

Tianhao Cong,1 Chao Yang,1 Qi Cao,2 Jinrui Ren,1 Yingen Luo,1 Pei Yuan,2 Bo Zheng,2 Yu Liu,1 Hongcai Yang,1 Wendi Kang,1 Aixin Ou,1 Xiao Li1 1Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comPurpose: Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms.Methods: Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms.Results: A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group.Conclusion: The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.Keywords: hepatocellular carcinoma, transarterial chemoembolization, immune infiltration, mast cell, glucose metabolism, hypoxic microenvironment

Nongnong Yang,1,&ast; Haiyan Ma,1,2 Mengyi Huang,1,&ast; Esther Yuet Ying Lau,3– 5 Daniel Yee Tak Fong,6 Meng Wang,7 Pengqiao Wang,1 Siyi Xu,8 Jiale Xu,1 Chen Jiang,1 Yi Luo,9 Runtang Meng1,2,&ast; 1School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Engineering Research Center of Mobile Health Management System, Ministry of Education, Hangzhou, Zhejiang, People’s Republic of China; 3Sleep Laboratory, Department of Psychology, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 4Centre for Psychosocial Health, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 5Centre for Religious and Spirituality Education, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 6School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 7Ophthalmology Center, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 8School of Nursing, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 9School of Nursing, Ningbo College of Health Sciences, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runtang Meng; Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mengruntang@hznu.edu.cn; mahaiyan@hznu.edu.cnPurpose: The World Health Organization-Five Well-Being Index (WHO-5) is widely used to assess subjective well-being. Nevertheless, measurement invariance and optimal cutoff point of the WHO-5 have not been examined in Chinese samples. We aimed to assess measurement properties of the Chinese version of the WHO-5 (WHO-5-C) among healthcare students.Patients and Methods: A two-wave longitudinal assessment was conducted among 343 Chinese healthcare students from September to November 2022. Measurement properties of the WHO-5-C were assessed through structural validity using confirmatory factor analysis (CFA), measurement invariance using multigroup CFA (MGCFA) and longitudinal CFA (LCFA), convergent validity using correlation analysis with the Self-Rated Health Questionnaire (SRHQ) and Patient Health Questionnaire-4 (PHQ-4), reliability using internal consistency and test–retest reliability, and optimal cutoff point using receiver operating characteristic (ROC) analysis.Results: The WHO-5-C demonstrated satisfactory structural validity with comparative fit index (CFI) of 0.968 at baseline and 0.980 at follow-up, and adequate measurement invariance in different sociodemographic variables at baseline (gender, age, major, home location, being only child, monthly household income, part-time job, physical exercise, hobby, frequency of visiting home, and stress coping strategy) (CFI changes [ΔCFI] = − 0.009– 0.003) and over a week (ΔCFI = − 0.006– 0.000). The WHO-5-C also had good internal consistency (Cronbach’s α = 0.907– 0.934; McDonald’s ω = 0.908– 0.935) and test–retest reliability (intraclass correlation coefficient [ICC] = 0.803). Convergent validity was supported by moderate correlations of the WHO-5-C with the SRHQ and PHQ-4. The optimal cutoff point of the WHO-5-C was found to be 50, with an area under the ROC curve of 0.882 at baseline data, with sensitivity of 0.803 and specificity of 0.762 at follow-up.Conclusion: The WHO-5-C demonstrated adequate measurement properties, especially concerning cross-sectional and longitudinal measurement invariance, with a recommended optimal cutoff point of ≥ 50 for assessing adequate level of psychological well-being in healthcare students.Keywords: WHO-5 Well-Being Index, subjective well-being, measurement properties, diagnostic performance, observational longitudinal design, healthcare students

Wenchao Huang,&ast; Huaxin Sun,&ast; Yan Tang,&ast; Yan Luo, Hanxiong Liu Department of Cardiology, The Third People’s Hospital of Chengdu, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxiong Liu, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu Cardiovascular Disease Research Institute, 82 Qinglong St. Chengdu, Sichuan, People’s Republic of China, Tel +86 18897966045, Email clin999@163.comPurpose: To investigate the effect and comprehensive predictive value of the platelet-to-lymphocyte ratio (PLR) for long-term recurrence in patients with atrial fibrillation (AF) post ablation.Patients and Methods: We retrospectively analysed 638 consecutive AF patients who underwent ablation, including 302 (47.3%) with paroxysmal AF and 336 (52.7%) with nonparoxysmal AF. Patients were grouped into the recurrence and nonrecurrence groups.Results: After a mean follow-up of 15.1± 9.3 months, 175 patients (27.4%) with AF had long-term recurrence, including 114 patients (33.9%) with nonparoxysmal AF and 61 patients (20.2%) with paroxysmal AF. In the entire cohort and in patients with nonparoxysmal AF, but not in those with paroxysmal AF, the PLR was significantly higher in the recurrence group than in the nonrecurrence group (P< 0.05). After adjusting for the APPLE score, the PLR as a continuous variable independently predicted AF recurrence (hazard ratio [HR], 1.003; 95% confidence interval [CI], 1.001– 1.005; P< 0.01). The addition of the PLR to the APPLE score improved its predictive ability for recurrence (the C-statistic value increased from 0.645 to 0.675, P=0.02; the net reclassification improvement was 0.221, 95% CI 0.049– 0.394, P=0.01; and the integrated discrimination improvement was 0.029, 95% CI 0.013– 0.045, P< 0.01). For nonparoxysmal AF, the PLR was stratified into tertiles, the PLR independently increased the nonparoxysmal AF recurrence risk after adjusting for multiple confounding factors (HR, 1.393; 95% CI, 1.102– 1.762; P< 0.01), and the addition of the PLR to the left atrial diameter improved its predictive ability for arrhythmia recurrence (the C-statistic value increased from 0.601 to 0.667, P< 0.01).Conclusion: The PLR is an independent predictive factor of long-term AF recurrence post ablation after adjusting for the APPLE score and can improve the predictive ability and clinical usefulness of the APPLE score. However, the PLR is an effective predictor of recurrence in patients with nonparoxysmal AF rather than in paroxysmal AF.Plain Language Summary: AF is a common cardiac arrhythmia that can be treated by catheter ablation. Even though the application of ablation has increased in clinical practice, the AF recurrence rate remains stubbornly high. Predicting the risk of recurrence would allow the optimization of AF treatment and management strategies. The impact of inflammation on atrial fibrillation recurrence is unperceived in the existing AF risk scores. Therefore, we investigated the predictive ability of the platelet-to-lymphocyte ratio, a marker of systemic inflammation that can be easily calculated following routine blood analysis, in estimating the risk of AF recurrence. We found that in the entire cohort and in patients with nonparoxysmal AF, but not in those with paroxysmal AF, the PLR ratio was significantly higher in the recurrence group than in the nonrecurrence group. Adding the platelet-to-lymphocyte ratio to the APPLE risk score improved its ability to predict AF in the entire cohort. In patients with nonparoxysmal AF, the addition of the RLR to the left atrial diameter improved its predictive accuracy. However, the PLR ratio did not predict recurrence of paroxysmal AF. Interestingly, we found that recurrence risk scores, such as the APPLE score and CHA2DS2-VASc, had no predictive value for nonparoxysmal AF. Therefore, the addition of the PLR to the APPLE score should be considered in evaluating AF recurrence risk for patients with an unknown type, and the addition of the PLR to the left atrial diameter should be performed to predict AF recurrence in patients with nonparoxysmal AF.Keywords: platelet-to-iymphocyte ratio, atrial fibrillation, recurrence, prediction model, inflammation, ablation

Yuanyuan Luo,&ast; Xiaojie Ma&ast; Oncology; Affiliated Hospital of North Sichuan Medical College; Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojie Ma, Email maxiaojie@nsmc.edu.cnPurpose: Construction of a nomogram model based on Thymidine kinase 1 (TK1) in combination with inflammatory indicators and tumor markers to predict the probability of recurrence in mid- to late-stage cervical cancer.Methods: One hundred fourteen instances of intermediate and advanced cervical cancer admitted to our hospital’s radiotherapy department between June 2017 and January 2023 were retrospectively studied. Logistic regression analysis includes variables relevant for univariate analysis. Meaningful indications from multifactor analysis were included in the nomogram model, the model’s correctness was evaluated using the C-index, and the model’s effectiveness was assessed using calibration curves, clinical decision curves, and clinical impact curves.Results: A nomogram model was created due to the logit regression analysis that revealed the squamous cell carcinoma antigen (SCC) and TK1 as independent recurrence predictors following cervical cancer radiation (P< 0.05). The C index and Area Under the Curve (AUC) were 0.79 (95% CI 0.67– 0.91). The AUC and C-index were both more extraordinary than those of TNM staging alone (C-index 0.57, 95% CI 0.43– 0.71) and SCC alone (C-index 0.67, 95% CI 0.51– 0.82). Calibration curves, Decision Curve Analysis (DCA), and clinical impact curves (CIC) indicate that the model predicts probabilities more accurately.Conclusion: The nomogram model based on TK1 combined with inflammatory markers and tumor markers is more reliable than the TNM staging and SCC systems alone for forecasting recurrence after radiotherapy in intermediate- and advanced-stage cervical cancer. It is also a cheap, practical, and simple-to-obtain model that can supplement the TNM staging system for forecasting prognosis and significantly enhances clinicians’ decision-making.Keywords: cervical cancer, thymidine kinase 1, inflammatory factors, prognosis, nomogram

Chao Gao,1,&ast; Yan Liu,2,&ast; Ting-Lin Zhang,3,&ast; Yi Luo,2,4,&ast; Jie Gao,3,&ast; Jian-Jian Chu,1 Bao-Feng Gong,1 Xiao-Han Chen,1 Tong Yin,1 Jian Zhang,2 You Yin1 1Department of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China; 4New Drug Discovery and Development, Biotheus Inc., Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Yin; Jian Zhang, Tel +86-21-81885463 ; +86- 21-25077150, Email yinyou179@163.com; zhangjian@xinhuamed.com.cnAbstract: Current therapies for Alzheimer’s disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed. Keywords: Alzheimer’s disease, nanoparticles, blood‒brain barrier, liposomes, bionanotechnology, neurodegenerative diseases

Qi Yang,1– 4 Yalan Luo,1– 3 Peng Ge,1– 3 Bowen Lan,1– 3 Jin Liu,1– 3 Haiyun Wen,1– 3 Yinan Cao,1– 3 Zhenxuan Sun,1– 3 Guixin Zhang,1– 3 Huiming Yuan,5 Lihua Zhang,5 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People’s Republic of China; 5CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, 116023, People’s Republic of ChinaCorrespondence: Hailong Chen, Email chenhailong@dmu.edu.cnBackground: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO. Plain Language Summary: Exosomes extracted from plasma/BALF of EMO-treated SAP rats show a substantial therapeutic impact on SAP-Associated ALI, with BALF-derived exosomes having a higher therapeutic effect than plasma-derived exosomes.EMO dramatically altered the miRNA expression patterns of plasma and BALF-derived exosomes in SAP rats.The lung protective effect of EMO in SAP rats is somewhat reliant on Novel-rno-miR-29a-3p expression.Keywords: severe acute pancreatitis, acute lung injury, emodin, exosome, microRNA

Yingxian Luo, Qiong Wu, Runtang Meng, Fuzhi Lian, Chen Jiang, Meiyu Hu, Yaxin Wang, Haiyan Ma School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mahaiyan@hznu.edu.cnObjective: To evaluate the associations between serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), with a focus on gender differences, and variations among women pre-and post-menopausal stages.Design: A retrospective cohort study.Setting: A large community-based survey was conducted every two years from 2010 to 2018 in Hangzhou, Zhejiang Province, Southeastern China.Participants: 10,218 participants (40 years or above) without CKD at baseline who underwent three physical examinations were enrolled. CKD was defined as an eGFR of less than 60 mL/min/1.73m2.Methods: Participants with SUA levels were divided into four groups (Q1-Q4) based on baseline SUA quartiles. The Q1 was the reference. By stratifying participants by gender, the relationships between SUA levels and eGFR were investigated using the generalized additive mixture model. The associations of SUA and the risk of incident CKD were examined using multivariate logistic regression models in the generalized estimating equation.Results: After adjusting for confounding variables, a nonlinear association between SUA and eGFR was observed in females, while an approximately linear relationship was observed in males, suggesting that elevated SUA levels are associated with renal function decline. Furthermore, the highest quartile of SUA was associated with a 2.16-fold (95% CI: 1.31– 3.58) increased risk of CKD in males and a 2.76-fold (95% CI: 1.59– 4.78) increased risk in females, compared with the lowest quartile. And the spline curves demonstrated a U-shaped pattern, suggesting a potential threshold effect of SUA on the risk of CKD. Additionally, Subgroup analyses revealed significant associations between elevated SUA levels with CKD in postmenopausal women, but not in premenopausal women.Conclusion: Elevated SUA levels are associated with an increased risk of CKD development and renal function decline in middle-aged and elderly individuals, particularly in postmenopausal women.Keywords: uric acid, estimated glomerular filtration rate, chronic kidney disease, Chinese cohort

Xiaoyu He,1,2 Yu Luo,2 Jianan Hao,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Luping Ren2 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Luping Ren, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86 311 859 889 75, Email renluping1122@163.comPurpose: Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS.Patients and Methods: A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters.Results: The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = – 0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients.Conclusion: Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.Keywords: ketosis onset, ketosis-prone type 2 diabetes, lipid metabolism, atherosclerosis, atherogenic index of plasma

Yanmei Luo,1,&ast; Jie Liu,2,&ast; Zhihui Jiang,3,&ast; Xinghai Yang,1 Song Lin,1 Xiaowen Mao1 1Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Surgery, Yijishan Hospital of Wannan Medical College, Wannan Medical College, Wuhu, People’s Republic of China; 3Department of General Surgery, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowen Mao; Song Lin, Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, No. 58 Guanggu Third Road, Donghu New Technology Development Zone, Wuhan City, 430070, Hubei Province, People’s Republic of China, Email xiaowenmao0927@163.com; yes888111@sina.cnPurpose: To compare and analyze the therapeutic effects of endoscopy-assisted laparoscopic surgery (EALS) and laparoscopic surgery (LS) in the treatment of gastric duplication cysts (GDCs).Patients and Methods: We reviewed the clinical data of children with GDCs who underwent surgical treatment at Hubei Maternal and Child Health Hospital, Yijishan Hospital of Wannan Medical College, and Qingdao Women and Children’s Medical Center from September 2014 to November 2022.Results: The study comprised 29 children with GDCs, including 14 in the EALS group and 15 in the LS group. There was no significant difference between the two groups in terms of age, sex, weight, and cyst size characteristics. There was a significant difference between the two groups in terms of average surgical time (P> 0.05), which was 1.100 ± 0.833 hours in the EALS group and 1.933 ± 0.159 hours in the LS group. There was a significant difference between the two groups (P< 0.05) in average intraoperative blood loss, which was 7.93 ± 3.81 milliliters in the EALS group and 11.80 ± 2.72 milliliters in the LS group. There was a significant difference between the two groups (P< 0.05) in average postoperative fasting time, which was 73.79 ± 8.36 hours in the EALS group and 114.1 ± 9.24 hours in the LS group. There was a significant difference between the two groups (P< 0.05) in average postoperative hospital stay, which was 10.21 ± 4.25 days in the EALS group and 14.47 ± 4.36 days in the LS group.Conclusion: EALS technology can not only shorten surgical time, accurately locate GDCs, reduce injuries, and decrease the probability of complications but also achieve treatment goals safely and reliably.Keywords: gastric duplication cyst, laparoscopic, endoscopic, surgery, children

Yanfeng Zhang,1 Yujia Luo,1 Yachao Ruan,2 Xiang Qian,3 Zhiying Feng1 1Department of Pain Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 3Stanford University School of Medicine Pain Management Center, Redwood City, CA, 94063, USACorrespondence: Zhiying Feng, Email fzy1972@zju.edu.cnIntroduction: Early diagnosis of SAPHO syndrome is easily confused with other common spine-related diseases and infections. There is currently no consensus regarding the diagnosis of SAPHO syndrome, and specific treatments are empirical because of its rarity.Case Presentation: A 62-year-old woman was referred to our department with complaints of low back and lower extremity pain for 2 years, 1.5 years after lumbar spine surgery, and recurrent low back pain for 1 year. Laboratory test results revealed elevated hs-CRP levels and erythrocyte sedimentation rate. Combined with her surgical history and lumbar CT results, adjacent segment degeneration (ASD) was first considered. NSAIDs, analgesics, and supplemental therapies were also administered. However, the patient’s symptoms were not significantly relieved. During re-examination, hyperkeratosis with active pustulosis was observed on the patient’s palms. Osteitis of the left sacroiliac joint was revealed on imaging. Skeletal ECT revealed a typical “horn sign”. The patient was diagnosed with SAPHO syndrome. Based on the original treatment, sulfasalazine enteric-coated tablets, adalimumab (a biological agent of TNF-α), pregabalin, and tramadol sustained-release tablets were administered. The patient reported that her pain was significantly relieved. He was discharged from the hospital and received adalimumab treatment (40 mg once per fortnight in the first 6 months and 40 mg once per month after month 6) in the outpatient clinic. The hyperkeratosis with active pustulosis on both palms fully recovered after 12 months of treatment. The patient was followed up 6 months after full recovery, and no recurrence was found in the symptoms of low back and lower extremity pain and palmar hyperkeratosis with active pustulosis.Conclusion: SAPHO syndrome should be suspected in patients present with osteoarticular and/or dermatological manifestations. Biological agents can be used to treat patients with refractory SAPHO syndrome.Keywords: SAPHO syndrome, low back pain, osteitis, pustulosis, adalimumab

Qixing Wu,&ast; Yiyuan Luo,&ast; Mingming Han, Juan Li, Fang Kang Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Kang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei City, Anhui Province, 230036, People’s Republic of China, Tel +86 18155127799, Email kangfang199771@163.comPurpose: This study aimed to investigate the value of the Pain Sensitivity Questionnaire (PSQ) for the prediction of postoperative pain and the relationship between pain sensitivity and postoperative pain in kidney donors undergoing living-related kidney transplantation.Patients and Methods: A total of 148 kidney donors were selected and the preoperative pain sensitivity questionnaire was administered the day before surgery. Kidney donors were assigned to low PSQ group (PSQ < 6.5, n = 76) or high PSQ group (PSQ ≥ 6.5, n = 72). The primary endpoint was the number of patient-controlled analgesia (PCA). Other outcomes included: the incidence of acute pain, flurbiprofen axetil remediation rate, the incidence of chronic pain, neuropathic pain assessment scale (Douleur Neuropathique 4 Questions, DN4), visual analog scale (VAS) at rest after surgery as well as the correlation between PSQ and QST (Quantitative Sensory Testing).Results: The low PSQ group had a significantly lower number of PCA than high PSQ group (P < 0.0001). The incidence of acute pain was 75% in low PSQ group and 100% in high PSQ group (P < 0.0001). Furthermore, flurbiprofen axetil remediation rate was lower in low PSQ group than that in high PSQ group (P = 0.042). The incidence of chronic pain was significantly lower in low PSQ group than in high PSQ group (6.6% vs 61.1%, P < 0.001). Moreover, DN4 was significantly lower in low PSQ group than that in high PSQ group (P < 0.001). The PSQ-mean was significantly negatively correlated with QST in kidney donors. VAS at rest for the low PSQ group were lower than those of the high PSQ group.Conclusion: The PSQ was found to be associated with the intensity or postoperative pain and might be used to screen patients prior to living-kidney transplantation.Keywords: pain, pain sensitivity, pain sensitivity questionnaire, kidney donor

Lihong Bao,1,&ast; Chunfen Peng,2,&ast; Jingting He,2 Chengqin Sun,1 Lijuan Feng,1 Yang Luo1 1Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Luo; Jingting He, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email yangluo@hust.edu.cn; hejingting@hust.edu.cnBackground: The role of fear-avoidance beliefs (FAB) in patients with chronic pain has been widely confirmed. However, few conclusions have been drawn about its role in postoperative patients.Objective: To explore the characteristics of FAB in postoperative patients after lung surgery as well as the effect of threat learning on FAB.Methods: Between May and September 2022, this study recruited 150 participants who had undergone thoracoscopic surgery. Variables such as age, gender, education, chronic pain, fear of pain, surgery method, pain intensity, FAB, cough, ambulation and threat learning were collected and subjected to correlation analysis and stepwise regression.Results: The correlation analysis revealed that FAB was associated with age (r = − 0.183, p < 0.05), gender (r = − 0.256, p < 0.01), and preoperative FOP-9 (r = 0.400, p < 0.01). Postoperative variables such as pain intensity (r = 0.574, p < 0.01), initiation day of ambulation (r = 0.648, p < 0.01), total numbers of ambulation (r = − 0.665, p < 0.01), and cough performance (r = − 0.688, p < 0.01) were correlated with FAB. Furthermore, FAB was highly correlated with indicators of threat learning: direct (r = 0.556, p < 0.01), observation (r = 0.655, p < 0.01), and instruction (r = 0.671, p < 0.01). The highest variance explanation model of stepwise regression which explained 52.8% of the variance including instruction (B=1.751; p< 0.01), direct (B=1.245; p< 0.01), observation (B=0.768; p< 0.01), age (B=− 0.085; p< 0.01), and surgery method (B=1.321; p< 0.05).Conclusion: Patients commonly experience FAB after lung surgery, which can directly affect their recovery behaviors such as ambulation and active coughing. The formation of FAB is influenced by threat learning, which suggests that controlling threat learning is important in preventing postoperative FAB.Keywords: fear-avoidance, threat learning, fear of pain, postoperative pain, lung surgery

Rong Wu,1,&ast; Yuan Luo,1,&ast; Pengyu Ren,2 Fengjiao Ran,1 Xiantao Yang,3 Manting Gu,3 Anxie Tuo,4 Zheng Yan1 1Department of Epidemiology and Health Statistics, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Guizhou Drug Evaluation Center, Guiyang, Guizhou, People’s Republic of China; 3School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 4School of Medical Humanities, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Yan, Department of Epidemiology and Health Statistics, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China, Email 2804573859@qq.comPurpose: This paper investigated the prevalence of mobile phone dependence (MPD) and its associated with learning burnout under the “double reduction” policy among adolescents in Guizhou Province in western China. In addition, the influence of the mediating mechanism of social support on this relationship was investigated.Methods: The sample was collected from 16,216 adolescents in West China’s Guizhou province, from December 2021 to January 2022 via multistage stratified random sampling. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) was used to assess the MPD, the Adolescent Student Burnout Scale (ASBI) was used to assess the learning burnout, and the Social Support Scale (SSS) was used to assess the social support. A hierarchical linear regression model was used to analyze the relationship between MPD, learning burnout, and social support. The mediating effect of social support between MPD and learning burnout was analyzed by structural equation model.Results: Prevalence of MPD was 26.4% among adolescents in Guizhou province in western China. After adjusting for confounding variables like demographics, multiple linear regression model has revealed that learning burnout positively predicted MPD and social support negatively predicted MPD. The structural equation model showed that 10.9% of the effect was explained by the mediating effect of social support.Conclusion: These findings could inform service delivery and policy formulation to reduce learning and avoid MPD in adolescents.Keywords: “double reduction” policy, mobile phone dependence, learning burnout, social support, adolescents

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Hai-bo Liu,1,&ast; Min Yang,2,&ast; Wan Li,2 Ting Luo,2 Yang Wu,2 Xiang-yu Huang,2 Yao-lei Zhang,3 Tao Liu,2 Yong Luo2,&ast; 1Department of Biomedical Engineer, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 2Department of Traditional Chinese Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 3Basic Medical Laboratory, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Luo, Department of Traditional Chinese Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China, Tel +86 28-86571619, Email yongl019@sina.comPurpose: Dispelling dampness, relieving turbidity and dredging collaterals decoction (DED), is a traditional Chinese medicine used in the treatment of hyperuricemia. We aimed to explore the effect and mechanism of DED in the treatment of hyperuricemia.Methods: The effects of DED (9.48, 4.74, and 2.37 g/kg/d) on potassium oxonate (750 mg/kg/d)-induced hyperuricemia in rats were evaluated by serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), and renal pathological changes. Network pharmacology was used to identify the effective components and targets of DED, and the key targets and signaling pathways for its effects on hyperuricemia were screened. Molecular docking was used to predict the action of DED. H&E, immunohistochemistry, WB, and PCR were used to validate the network pharmacology results.Results: DED can effectively alleviate hyperuricemia, inhibit UA, CRE, BUN, and xanthine oxidase (XOD) activity, and reduce renal inflammatory cell infiltration and glomerular atrophy. The experiment identified 27 potential targets of DED for hyperuricemia, involving 9 components: wogonin, stigmasterol 3-O-beta-D-glucopyranoside, 3β-acetoxyatractylone, beta-sitosterol, stigmasterol, diosgenin, naringenin, astilbin, and quercetin. DED can relieve hyperuricemia mainly by inhibiting RAGE, HMGB1, IL17R, and phospho-TAK1, and by regulating the AGE-RAGE and IL-17 signaling pathways.Conclusion: DED can alleviate hyperuricemia by inhibiting XOD activity and suppressing renal cell apoptosis and inflammation via the AGE-RAGE signaling pathway and IL-17 signaling pathway. This study provides a theoretical basis for the clinical application of DED.Graphical Abstract: Keywords: dispelling dampness, relieving turbidity, dredging collaterals, hyperuricemia, network pharmacology

Guoping Dong,1,2 Fangying Fan,1,2 Yao He,3 Yanchun Luo,1 Jie Yu,1,2 Ping Liang1,2 1Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 3Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, People’s Republic of ChinaCorrespondence: Ping Liang; Jie Yu, Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel +86-10-66939530 ; +86-10-66937963, Email liangping301@126.com; jiemi301@163.comBackground: Extrahepatic metastasis in hepatocellular carcinoma (HCC) greatly limits the prognostic survival of HCC patients. Levels of preoperative peripheral lymphocyte subsets and cytokines in the serum for predicting extrahepatic spread of hepatocellular carcinoma are still not common in clinical practice. The aim of this study is to investigate the value and mechanisms of peripheral lymphocyte subsets and cytokines in predicting extrahepatic spread of HCC.Methods: We used a retrospective design to analyze data pertaining to a total of 380 patients with HCC who were examined for peripheral T-lymphocyte subsets before receiving microwave ablation. We performed Cox regression analysis to screen out independent risk factors and used pathology specimens from the patients and public databases of liver cancer to investigate the correlation between cytokines and intra-tumor immune cells.Results: The CD4low group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD4high group (80% vs 69%, 67% vs 51%, and 57% vs 39%, respectively; HR 1.7 (1.2, 2.3), P = 0.0019). Similarly, the CD8high group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD8low group (65% vs 78%, 46% vs 64%, and 34% vs 54%, respectively; HR 0.6 (0.4, 0.8), P < 0.001). Patients with the CD4high/CD8low phenotype had significantly worse metastasis-free survival times compared to other patients (HR 2.0 (1.5, 2.8), P < 0.001). Additionally, T lymphocyte-specific genes (CD4, CD8) were correlated with CCL5 expression, which was also positively correlated with the level of intra-tumoral infiltrating CD8 T cells and the prognosis of HCC patients.Conclusion: Both CD4+ and CD8+ T lymphocyte subsets were independent risk factors for extrahepatic metastasis in HCC. Serum CCL5 levels could indicate the infiltration level of intra-tumoral CD8+ T cells and the risk of extrahepatic metastasis in HCC patients, aiding in patient risk stratification for metastasis.Graphical Abstract: Keywords: cytokine CCL5, extrahepatic metastasis of hepatocellular carcinoma, peripheral lymphatic subset analysis, cytotoxic CD8+ T cells

Jiarui Zhang,1,&ast; Yichun Qin,2,&ast; Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,&ast; Haixia Zhou1,&ast; 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes

Yuting Luo,1,&ast; Zhaowang Guo,2,&ast; Ying Li,1,&ast; Hui Ouyang,1 Shanfeng Huang,1 Yuanli Chen,3 Kenan Li,1 Yuxin Ji,1 Hongqiong Zhu,1 Wentao Luo,1 Xu Liu,1,4 Xinghua Li,1 Jinyu Xia,1 Xi Liu1 1Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China; 2Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China; 3Department of Hospital Infection Control, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Liu; Xinghua Li, Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, 52 Meihua East Road, Xiangzhou District, Zhuhai, 519000, People’s Republic of China, Tel/Fax +86-756-252-8592, Email liuxi26@mail.sysu.edu.cn; lixh79@mail.sysu.edu.cnObjective: The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection.Methods: A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model.Results: A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135– 70,155] vs 31,489 [14,894– 101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135– 70,155] vs 30,960 [16,475– 90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT.Conclusion: Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.Keywords: antimicrobial resistance, bacterial culture-positive, empirical antibiotic therapy, patient outcome, multidrug-resistant organism

Yuntong Yang, Yanhong Luo, Ming Chen, Jie Zhai Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yanhong Luo, Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China, Tel +86-1868 486 0548, Email luoyanhong2006@126.comPurpose: Mobile phone addiction has motivated a widespread concern in recent years. From a developmental perspective, this study explored the predictive relations between life events, boredom proneness (BP), and mobile phone addiction tendency (MPAT) among undergraduate students. It also tested the longitudinal mediation of BP between life events and MPAT.Methods: Five hundred and eighty-four undergraduate students completed the Mobile Phone Addiction Tendency Scale, the Adolescent Self-Rating Life Events Checklist, and the Boredom Proneness Scale-Short Form. A longitudinal mediation analysis based on latent growth modeling was conducted to test the hypothesized relationships among life events, BP and MPAT.Results: Latent growth modeling (LGM) showed that the BP and MPAT of undergraduate students both increased linearly. A longitudinal model based on LGM showed that negative life events both directly and indirectly affected the initial level and the growth rate of the MPAT through the mediating effect of the initial level of BP.Conclusion: These results reveal that negative life events are an indicator of the development of MPAT. It has practical implications for calling for adopting health coping styles when facing negative life events. Supported for reducing college students’ boredom proneness in order to lessen the tendency towards mobile phone addiction to improve their mental health.Keywords: mobile phone addiction, life events, boredom proneness

Zhigang Liu,1,&ast; Jiahui Liang,1,&ast; Hangzhan Hu,1,&ast; Mengli Wu,1,&ast; Jingjing Ma,1 Ziwei Ma,1 Jianing Ji,1 Hengyi Chen,2 Xiaoquan Li,1 Zhizeng Wang,1,2 Yang Luo2,3 1Joint National Laboratory for Antibody Drug Engineering, Clinical Laboratory of the First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China; 2Center of Smart Laboratory and Molecular Medicine, Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China; 3College of Life Science and Laboratory Medicine, Kunming Medical University, Kunming, 650500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhizeng Wang, Joint National Laboratory for Antibody Drug Engineering, Clinical Laboratory of the First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, 475004, People’s Republic of China, Tel +86 15093628687, Email wzhzeng@126.com Yang Luo, Center of Smart Laboratory and Molecular Medicine, Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China, Tel +86 13594088001, Email luoy@cqu.edu.cnIntroduction: Neutralizing antibodies (NAbs) are essential for preventing reinfection with SARS-CoV-2 and the recurrence of COVID-19; nonetheless, the formation of NAbs following vaccination and infection remains enigmatic due to the lack of a practical and effective NAb assay in routine laboratory settings. In this study, we developed a convenient lateral flow assay for the rapid and precise measurement of serum NAb levels within 20 minutes.Methods: Receptor-binding domain-fragment crystallizable (RBD-Fc) and angiotensin-converting enzyme 2-histidine tag (ACE2-His) were expressed by the eukaryotic expression systems of Spodoptera frugiperda clone 9 and human embryonic kidney 293T, respectively. Then, colloidal gold was synthesized and conjugated with ACE2. After optimizing various operating parameters, an NAb lateral flow assay was constructed. Subsequently, its detection limit, specificity, and stability were systematically evaluated, and clinical samples were analyzed to validate its clinical feasibility.Results: RBD-Fc and ACE2-His were obtained with 94.01% and 90.05% purity, respectively. The synthesized colloidal gold had a uniform distribution with an average diameter of 24.15 ± 2.56 nm. With a detection limit of 2 μg/mL, the proposed assay demonstrated a sensitivity of 97.80% and a specificity of 100% in 684 uninfected clinical samples. By evaluating 356 specimens from infected individuals, we observed that the overall concordance rate between the proposed assay and conventional enzyme-linked immunosorbent assay was 95.22%, and we noticed that 16.57% (59/356) of individuals still did not produce NAbs after infection (both by ELISA and the proposed assay). All the above tests by this assay can obtain results within 20 minutes by the naked eye without any additional instruments or equipment.Conclusion: The proposed assay can expediently and reliably detect anti-SARS-CoV-2 NAbs after infection, and the results provide valuable data to facilitate effective prevention and control of SARS-CoV-2.Clinical trial registration: Serum and blood samples were used under approval from the Biomedical Research Ethics Subcommittee of Henan University, and the clinical trial registration number was HUSOM-2022-052. We confirm that this study complies with the Declaration of Helsinki.Keywords: clinical detection, colloidal gold, neutralizing antibody, point-of-care test, SARS-CoV-2

Yonghan Luo, Yanchun Wang Second Department of Infectious Disease, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yanchun Wang, Second Department of Infectious Disease, Kunming Children’s Hospital, Kunming, Yunnan, 650000, People’s Republic of China, Email Wangyanchun0204@163.comObjective: To explore the clinical characteristics of necrotizing pneumonia (NP) caused by different pathogens.Methods: A total of 282 children with NP admitted to Kunming Children’s Hospital from January 2014 to November 2022 were enrolled. The clinical data of all children was collected. According to the different pathogens causing NP, the children were divided into three groups: the Mycoplasma pneumoniae necrotizing pneumonia (MPNP) group, the bacterial necrotizing pneumonia (BNP) group, and necrotizing pneumonia with no pathogen detected (NNP) group. The basic information, symptoms, signs, laboratory tests, radiological features, treatment, and prognosis of the three groups were compared.Results: Among the 282 cases of NP, there were 62 (22.0%) cases of MPNP, 98 (34.75%) cases of BNP, and 142 (50.35%) cases of NNP. The most common bacteria causing NP were Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Acinetobacter baumannii, respectively. Most clinical features of the three groups were statistically significant. The area under the concentration curve of white blood cell, C-reactive protein, albumin, neutrophil percentage, and fibrinogen in differentiating MPNP from BNP were 0.743 (0.638– 0.849), 0.797 (0.711– 0.883), 0.766 (0.671– 0.861), 0.616 (0.509– 0.724), and 0.634 (0.523– 0.744), respectively. The decision curve showed that white blood cells, albumin, and C-reactive protein had good clinical application in differentiating MPNP from BNP. All patients were improved and discharged without death.Conclusion: Bacteria are the most common cause of NP, and the most common bacteria are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. NP with no pathogen detected accounted for a large proportion. white blood, C-reactive protein, and albumin can identify the pathogens of NP. Patients with BNP were more severe, had a longer hospital stay, and were more likely to undergo closed drainage and surgery.Keywords: pathogen, children, necrotizing pneumonia, clinical features

Xiaoling Zhang, Xuting Jin, Jiajia Ren, Jueheng Liu, Haichang Ma, Xiaoming Fang, Huifan Zhang, Yujie Zhao, Yanli Hou, Yanni Luo, Lei Guo, Qi Ma, Ya Gao, Jingjing Zhang, Jiamei Li, Xiaochuang Wang, Gang Wang Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Xiaochuang Wang; Gang Wang, Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xi 5 Lu, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86-029-8767-9630 ; +86-029-8767-9633, Email dr_xc_wang@163.com; gang_wang@xjtu.edu.cnPurpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB.Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model.Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063– 6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353– 2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433– 3.142) nor multivariable (OR: 0.357, 95% CI: 0.097– 1.320) models.Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.Keywords: appropriate empirical antibiotics, hospital-acquired pneumonia, carbapenem-resistant, gram-negative bacteria, ICU mortality

Jun Huang,&ast; Peizhuang Zhao,&ast; Jialing Shi, Jiajia Ning, Zhen Wang, Yihua Luo, Jingqian Qin, Xue Huang Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been proven to participate in the occurrence and development of multiple cancers. However, the functional role of P4HA3 in the tumor immune microenvironment (TIME) of colon adenocarcinoma (COAD) and the prognosis of COAD patients has not been clarified. This study aimed to elucidate the immunological role and prognostic value of P4HA3 in COAD.Methods: P4HA3 expression in COAD tissues was analyzed via experiments and a bioinformatics algorithm. Based on the COAD patients in The Cancer Genome Atlas database, we comprehensively evaluated whether the expression levels of P4HA3 affected clinical prognosis, TIME, and immunotherapy of COAD using the R platforms and several public databases, including GEPIA, TIMER, TISIDB, and TCIA.Results: The results of the pan-cancer analysis indicated that P4HA3 expression was significantly different in most tumor tissues compared with normal tissues. P4HA3 was overexpressed in COAD tissues, and overexpression of P4HA3 was associated with a worse overall survival and a shorted progression-free interval in COAD patients. The expression of P4HA3 was positively correlated with pathological stage, T stage, N stage, perineural infiltration, and lymphatic infiltration. There were significant correlations of P4HA3 expression levels with immune cell infiltration and their makers, as well as immunomodulators, chemokines, and microsatellite status. Moreover, overexpression of P4HA3 was associated with a lower response rate to immunotherapy in the IMvigor210 cohort.Conclusion: Overexpression of P4HA3 is closely related to the poor prognosis of COAD patients, and P4HA3 is a potential target for immunotherapy in COAD patients.Keywords: P4HA3, colon adenocarcinoma, prognosis, immunotherapy, tumor immune microenvironment

Yonghan Luo, Yanchun Wang Second Department of Infectious Disease, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yanchun Wang, Second Department of Infectious Disease, Kunming Children’s Hospital, Kunming, Yunnan, 650000, People’s Republic of China, Email wangyanchun0204@163.comObjective: To analyze the predictive factors for necrotizing pneumonia (NP) in children with Mycoplasma pneumoniae pneumonia (MPP) and construct a prediction model.Methods: The clinical data with MPP at the Children’s Hospital of Kunming Medical University from January 2014 to November 2022 were retrospectively analyzed. Eighty-four children with MPP who developed NP were divided into the necrotizing group, and 168 children who did not develop NP were divided into the non-necrotizing group by propensity-score matching. LASSO regression was used to select the optimal factors, and multivariate logistic regression analysis was used to establish a clinical prediction model. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the nomogram. Clinical decision curve analysis was used to evaluate the clinical predictive value.Results: LASSO regression analysis showed that bacterial co-infection, chest pain, LDH, CRP, duration of fever, and D-dimer were the influencing factors for NP in children with MPP (P < 0.05). The results of ROC analysis showed that the AUC of the prediction model established in this study for predicting necrotizing MPP was 0.870 (95% CI: 0.813– 0.927, P < 0.001) in the training set and 0.843 (95% CI: 0.757– 0.930, P < 0.001) in the validation set. The Bootstrap repeated sampling for 1000 times was used for internal validation, and the calibration curve showed that the model had good consistency. The Hosmer-Lemeshow test showed that the predicted probability of the model had a good fit with the actual probability in the training set and the validation set (P values of 0.366 and 0.667, respectively). The clinical decision curve showed that the model had good clinical application value.Conclusion: The prediction model based on bacterial co-infection, chest pain, LDH, CRP, fever duration, and D-dimer has a good predictive value for necrotizing MPP.Keywords: mycoplasma pneumonia, necrotizing pneumonia, nomogram, children

Yi Xiong,1,2,&ast; Yani Luo,2,&ast; Ting Yuwen,2,&ast; Jiana Li,2 Rongchang Chen,3 Fei Shi1 1Emergency Department, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, People’s Republic of China; 3Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Email chenrc@vip.163.com Fei Shi, Email shi.fei@szhospital.comPurpose: Airway remodeling is a significant pathological change of asthma. This study aimed to detect differentially expressed microRNAs in the serum of asthma patients and airway smooth muscle cells (ASMCs) of asthmatic mice, exploring their role in the airway remodeling of asthma.Methods: The differentially expressed microRNAs in the serum of mild and moderate-severe asthma patients compared to healthy subjects were revealed using the “limma” package. Gene Ontology (GO) analysis was used to annotate the functions of microRNA target genes. The relative expressions of miR-107 (miR-107-3p in mice sharing the same sequence) in the primary airway smooth muscle cells (ASMCs) of the asthma mice model were tested by RT-qPCR. Cyclin-dependent kinases 6 (Cdk6), a target gene of miR-107, was predicted by algorithms and validated by dual-luciferase reporter assay and Western blot. The roles of miR-107, Cdk6, and protein Retinoblastoma (Rb) in ASMCs were examined by transwell assay and EDU KIT in vitro.Results: The expression of miR-107 was down-regulated in both mild and moderate-severe asthma patients. Intriguingly, the level of miR-107 was also decreased in ASMCs of the asthma mice model. Up-regulating miR-107 suppressed ASMCs’ proliferation by targeting Cdk6 and the phosphorylation level of Rb. Increasing the expression of Cdk6 or suppressing Rb activity abrogated the proliferation inhibition effect of ASMCs induced by miR-107. In addition, miR-107 also inhibits ASMC migration by targeting Cdk6.Conclusion: The expression of miR-107 is down-regulated in serums of asthma patients and ASMCs of asthmatic mice. It plays a critical role in regulating the proliferation and migration of ASMCs via targeting Cdk6.Keywords: asthma, microRNA microarray, airway smooth muscle cells, miR-107, Cdk6

Yinhua Luo,1,&ast; Jinbo Zhao,2,&ast; Xueru Chen,3,&ast; Rui Huang,2 Ling Hou,2 Ke Su,2 Yuhua Lei,2 Yuanhong Li1,2 1Department of Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Shiyan, Hubei Province, 442000, People’s Republic of China; 2Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, Hubei Province, 445000, People’s Republic of China; 3Department of General Practice, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Li, Cardiovascular Disease Center, Central Hospital of Tujia and Miao Autonomous Prefecture, Hubei University of Medicine, Enshi Prefecture, People’s Republic of China, Email shaoyiju75482@163.comBackground: Ischemic cardiomyopathy (ICM) with high mobility and mortality is closely linked to immunology, oxidative stress, inflammatory response and so on. Early diagnosis counts for the effective treatment of ICM. However, there are still no distinctive diagnostic signatures. This research aims to investigate effective signatures and build the diagnostic model for ICM.Methods: The Gene Expression Omnibus was used to retrieve the microarray data of GSE9800 and GSE580, which were obtained from tissue biopsy samples. Differentially expressed genes (DEGs), GO, and KEGG analyses were then carried out on the microarray data. The PPI network was constructed via STRING database.Following that, CIBERSORT techniques in conjunction with the LM22 feature matrix were used to assess the immune infiltration of the samples.The expression of a few chosen genes served as the predictor variable, and the occurrence of ICM served as the responder variable, in the construction of the best subset stepwise regression model.Results: A total of 28 DEGs were found. And according to the GO and KEGG studies, numerous biological processes were enriched. Patients with ICM and their normal counterparts had considerably distinct immune cell types infiltrating. For the construction of the PPI network, the top 20 most significant DEGs were selected and were used to build the original regression model. The optimal subset screened using stepwise regression analysis contained three pivotal genes (SCD, SNX25, WNT7B) and the area under the curve (AUC) values in this model was 0.891.Conclusion: We identified several possible hub genes, including SCD, SNX25, and WNT7B, which may be strongly related to the development of ICM. Based on the three genes, the logistic regression model could be used to accurately diagnose ICM patients.Keywords: ischemic cardiomyopathy, ICM, immunology, inflammatory responses, diagnosis, differently expressed genes, bioinformatic analysis, the optimal subset stepwise regression