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Siqi Jiang,1,2 Linlin Ou,1,2 Yueqi Wang,1,2 Kai Su,1,2 Zhipei Chen,1,2 Lihong He,1,2 Xun Xu,1,2 Bin Cheng,1,2 Juan Xia,1,2 Zhaona Fan1,2 1Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhaona Fan; Juan Xia, Hospital of Stomatology, Sun Yat-sen University, No. 56 Lingyuanxi Road, Guangzhou, Guangdong, 510055, People’s Republic of China, Tel +86 20 87394123 ; +86 20 83741891, Fax +86 20 83822807, Email fanzhn3@mail.sysu.edu.cn; xiajuan@mail.sysu.edu.cnPurpose: Circular RNAs (circRNAs) are associated with the progression of tumors and hold promise as potential biomarkers for liquid biopsy. Among these, the role of circPRMT5 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. This study aims to examine the role and underlying mechanisms of circPRMT5 in the progression of HNSCC and to assess its potential diagnostic value in saliva exosomes.Methods: The expression of circPRMT5 and its clinical significance in HNSCC were investigated. Both in vitro and in vivo studies were performed to elucidate the biological role of circPRMT5 in HNSCC. RNA sequencing was utilized to identify downstream mechanisms. To evaluate and validate these mechanisms, Western blotting, RNA-FISH, immunofluorescence, immunohistochemistry, RIP, and rescue experiments were employed. Finally, salivary exosomes were isolated, and the expression levels of circPRMT5 were assessed using qRT-PCR.Results: The upregulation of circPRMT5 in HNSCC tissues was identified to be correlated with cervical lymph node metastasis and advanced clinical T stage. Both in vitro and in vivo experiments manifested that circPRMT5 promoted the proliferation and metastasis of HNSCC. Mechanistically, circPRMT5 was demonstrated to directly bind to and stabilize the insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), which, subsequently, binds to and stabilizes the serpin family E member 1 (SERPINE1) mRNA, thereby enhancing SERPINE1 expression. Furthermore, rescue experiments indicated that the proliferative, invasive, and migratory effects of circPRMT5 in HNSCC were dependent on the involvement of IGF2BP3 and SERPINE1. Notably, circPRMT5 levels were significantly elevated in the saliva exosomes of HNSCC patients, exhibiting substantial diagnostic value.Conclusion: CircPRMT5 exhibits significant diagnostic utility through salivary exosomes and plays a crucial role in promoting the progression of HNSCC via the IGF2BP3-SERPINE1 pathway. These findings highlight the potential of circPRMT5 as a noninvasive diagnostic biomarker and a therapeutic target for patients with HNSCC. Keywords: head and neck cancer, circPRMT5, IGF2BP3, SERPINE1, salivary exosomes

Yunheng Liu,1,* Longqing Si,1,* Yuxuan Jiang,1,* Shaojing Jiang,2 Xiaokang Zhang,1 Song Li,1 Jing Chen,1 Jinghui Hu2 1School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 2Yantai Engineering Research Center for Digital Technology of Stomatology, Characteristic Laboratories of Colleges and Universities in Shandong Province for Digital Stomatology, Institute of Stomatology, Binzhou Medical University, Yantai, 264003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Chen, School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, People’s Republic of China, Email chenjingbyyxy@163.com Jinghui Hu, Yantai Engineering Research Center for Digital Technology of Stomatology, Characteristic Laboratories of Colleges and Universities in Shandong Province for Digital Stomatology, Institute of Stomatology, Binzhou Medical University, Yantai, 264003, People’s Republic of China, Email bykfhjh@163.comAbstract: The metabolic activity of tumor cells leads to the acidification of the surrounding microenvironment, which provides new strategies for the application of nanotechnology in cancer therapy. Researchers have developed various types of pH-responsive nanomaterials based on the tumor acidic microenvironment. This review provides an in-depth discussion on the design mechanisms, drug-loading strategies, and application pathways of tumor acidic microenvironment-responsive nanodrug delivery systems. These materials trigger drug release upon reaching the tumor microenvironment, enhancing therapeutic targeting and reducing toxicity to healthy cells. pH-responsive nanomaterials include organic nanomaterials, inorganic nanomaterials, and composite nanomaterials. Additionally, this review outlines the drug-loading strategies, application prospects, and challenges of pH-responsive nanomaterials, aiming to promote the development and clinical translation of this field.Keywords: tumor microenvironment, pH response, nanocarriers, drug-loading strategies, drug delivery system

Shijie Jiang,1,* Qiyu Jia,2,* Zhenlei Peng,1,* Qixuan Zhou,1 Qizhong Yi,1 Zhiguo An1 1Xinjiang Clinical Research Center for Mental Health, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2Department of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qizhong Yi; Zhiguo An, Xinjiang Clinical Research Center for Mental Disorder, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China, Email qizhongyi@126.com; 37989344@qq.comPurpose: This study aims to investigate whether academic burnout alleviates or exacerbates internet dependence among college students with depression and anxiety. Moreover, it intends to construct a moderated mediation model to examine how academic burnout moderates the relationship between depressive and anxious emotions and internet addiction and how social support mediates this relationship to determine the psychological motivations underlying addiction.Methods: A questionnaire survey was conducted using the simple random sampling method, which yielded 757 valid responses (response rate: a 93.11% response rate). The sample included 274 males and 466 females, with an average age of 20.90 years (± 1.48). Hierarchical regression analysis was employed for data analysis.Results: Anxiety and depressive symptoms directly affect the internet dependence of university students and indirectly affect it through the mediating role of social support. Academic burnout moderates the relationship between negative emotions and internet addiction, with high levels of academic burnout potentially decreasing the internet dependence of students experiencing negative emotions. We proposed a psychological self-regulation mechanism theory, which posits that learned helplessness may intensify the emotional symptoms of anxiety and depression, which is reflected in reduced internet use behavior.Conclusion: High levels of academic burnout can exacerbate symptoms of depression and anxiety, significantly reducing students’ interest in activities. For these students, a decrease in internet addiction may not be a positive sign; instead, it could indicate worsened depression and anxiety. This finding underscores the need for close monitoring of and intervention implementation for college students experiencing high levels of burnout and symptoms of depression or anxiety.Keywords: academic burnout, internet addiction, depression, anxiety, social support

Qingqing Zhang,1,2,&ast; Jing Zheng,1,&ast; Guoyu Wang,1,3 Suyun Jiang,1 Peng Gao,1 Si Sun,1 Xiangwei Ding,3 Yucheng Wu3 1Department of Pan-Vascular Management Center, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucheng Wu; Xiangwei Ding, Email 2567181759@qq.com; dingxw1208@126.comObjective: To determine the prevalence of Cardiovascular-Kidney-Metabolic (CKM) Syndrome and identify risk factors, including occupational factors, lifestyle factors and clinical measurements, and female-specific risk enhancers among healthcare workers in China.Methods: A cross-sectional study was conducted among healthcare workers at Taizhou People’s Hospital between April and May 2024. We collected data through surveys and laboratory results. Univariate and multivariate logistic regression analyses were performed to identify predictors of CKM syndrome and female-specific risk enhancers.Results: A total of 1110 participants were recruited (197 male; 913 female; mean age 34.8± 7.9). Almost 90% of male healthcare workers and 60% of female healthcare workers met the criteria for CKM syndrome (stage 1 or higher). Additionally, most male CKM syndrome patients were in stages 2– 3 (53.81%), while most female CKM syndrome patients were in stage 1 (35.82%). Multivariate logistic regression analysis revealed that, compared to those with over 20 years of work duration, a work duration of less than 10 years was a protective factor for CKM Syndrome. Additionally, more than 8 hours of sedentary time was identified as a risk factor compared to less than 2 hours (OR = 1.376, 95% CI 1.027– 1.844, P < 0.05). Receiver operating characteristic analysis showed that body mass index (BMI) was superior to fasting plasma glucose, glycated hemoglobin, triglycerides, and the triglyceride glucose product index in predicting CKM Syndrome, with area under the curve values of 0.884 vs 0.638, 0.708, 0.745, and 0.761, respectively (P < 0.05 for all). BMI was identified as an independent risk factor for female-specific risk enhancers.Conclusion: CKM syndrome is prevalent among healthcare workers in Chinese tertiary hospitals, with males generally presenting at more advanced stages than females. BMI is a key predictor of CKM syndrome and female-specific risk enhancers.Keywords: cardiovascular-kidney-metabolic syndrome, BMI, healthcare workers, triglyceride glucose product index

Yehong Xie, Shunning Jiang, Qiaoling Liang, Xuezhu Hu, Dahai He, Xiaoheng Wu Chengdu University of Traditional Chinese Medicine Third Clinical Medical College/Affiliated Third Hospital, Pidu District Traditional Chinese Medicine Hospital, Chengdu, Sichuan, 611730, People’s Republic of ChinaCorrespondence: Xiaoheng Wu, Pidu District Traditional Chinese Medicine Hospital, Chengdu, Sichuan, 611730, People’s Republic of China, Email xiaohengwu1997@126.comAbstract: Moraxella catarrhalis (MC) is an aerobic Gram-negative cocci known to cause respiratory tract infections in humans as an opportunistic pathogen, with infections in other body parts being rare. This case involves an elderly female patient with a medical history of hypertension, type 2 diabetes, coronary heart disease, and osteoporosis. Following coronary angiography and lumbar spine surgery prompted by lower back and left lower limb pain, the patient developed persistent pus discharge from the lumbar spine wound post-surgery, which did not respond to conventional anti-infection therapy, leading to her transfer to our hospital. Upon examination, Direct Radiography (DR) diagram revealed gas accumulation and bone curling in the 4– 5 intervertebral space, muscle layer, and fascia layer of the lumbar vertebrae. Subsequent culture of the wound pus confirmed the presence of MC, resulting in a diagnosis of postoperative lumbar spine infection. Treatment involved antibiotics administration, lesion clearance, spinal exploration, and autologous iliac bone transplantation for fusion, alongside the management of glucose levels and hypertension, anticoagulation therapy, as well as the use of Duhuo Jisheng Decoction to promote blood circulation and eliminate blood stasis. Following this comprehensive treatment approach, the patient achieved a full recovery and was discharged. To the best of our knowledge, this is the first reported case of Moraxella catarrhalis infection following lumbar spinal fixation and fusion in Sichuan Province, China. The exact cause of infection in this case remains unclear. However, this case emphasizes the importance of considering the colonization site and infection mechanism of MC beyond the respiratory tract, underscoring the need for vigilance in clinical practice beyond typical infection sites.Keywords: Moraxella catarrhalis, lumbar spinal, fixation and fusion, case report

Yanling Huang,1,&ast; Bing Li,1,&ast; Suibin Feng,2,&ast; Sifen Jiang,1 Kun Zeng1,3 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Pediatric Urology Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 3Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Zeng, School of Nursing, Guangdong Pharmaceutical University, No. 283, Jianghai Avenue, Haizhu District, Guangzhou City, Guangdong Province, 510310, People’s Republic of China, Tel +86 13790300213, Email zengkun660524@163.comPurpose: This study aimed to investigate the current state of empathy for pain among clinical nurses, analyze the relationship between resilience and empathy for pain, and explore the mediating effects of coping styles.Methods: This was a multicenter cross-sectional study conducted among 1601 clinical nurses in Guangdong Province, China. The convenience sampling method was used to collect data from Sociodemographic information, the 14-Item Resilience Scale, the Simplified Coping Style Questionnaire, and the Chinese version of the Empathy for Pain Scale from June to September 2023. To analyze the relationship between resilience, coping styles, and empathy for pain among clinical nurses with descriptive statistics, Spearman correlation analysis, and mediation analysis.Results: The empathy for pain score among Chinese clinical nurses was 2.92 ± 0.79, with the empathy reactions dimension at 3.56 ± 0.74, and the body and mind discomfort reactions dimension at 2.70 ± 0.89. Clinical nurses’ resilience was positively related to the coping styles and the empathy reactions dimension, whereas negatively associated with the body and mind discomfort reactions dimension. Coping styles were negatively related to the empathy for pain and the body and mind discomfort reactions dimension, whereas positive with the empathy reactions dimension. Coping styles partially mediated between resilience and empathy reactions dimension (β=0.127, 95% CI: 0.070~0.183), accounting for 56.19% of the total effect. There were suppressing effects of coping styles between resilience and empathy for pain (β=− 0.157, 95% CI: − 0.189~-0.126), the body and mind discomfort reactions dimension (β=− 0.172, 95% CI: − 0.203~-0.142).Conclusion: The effects of resilience on clinical nurses’ empathy for pain were partially mediated and suppressed by coping styles. During clinical pain management, nursing administrators should focus on developing clinical nurses’ resilience and positive coping strategies to improve nurses’ physical and mental health, optimize pain management, and foster a heightened sense of empathy for pain.Keywords: resilience, coping styles, empathy for pain, mediating effect, suppressing effect

Shandong Jiang,1,2 Libin Hu,1,2 Hang Zhou,1,2 Jianan Wu,1,2 Jiayin Zhou,1,2 Xian Yu,1,2 Gao Chen1,2 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, 310016, People’s Republic of ChinaCorrespondence: Gao Chen, Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, 310009, People’s Republic of China, Email d-chengao@zju.edu.cnAbstract: Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome’s research from laboratory to clinical practice. Keywords: intracerebral hemorrhage, exosomes, extracellular vesicles, microRNAs, stem cells

Na Chen,1,2 Xuben Yu,3 Lu Li,1 Ping Yang,1 Rong Dong,1,4 Yizhen Huang,1,5 Xiao Ling,1,6 Qiaoqiao Shentu,1,7 Wenqiao Yu,8 Saiping Jiang1 1Department of Clinical Pharmaceutical, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Clinical Pharmacy, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 6Department of Pharmacy, The People’s Hospital of Yuhuan, Taizhou, People’s Republic of China; 7Department of Pharmacy, Dongyang Red Cross Hospital, Jinhua, People’s Republic of China; 8Department of Hepatobiliary and Pancreatic Surgery and Intensive Care Unit, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Saiping Jiang; Wenqiao Yu, Email j5145@zju.edu.cn; yuwenqiao1980@zju.edu.cnBackground: The population pharmacokinetics of nirmatrelvir/ritonavir (NIR/RIT) has not yet been described for critically ill adult patient.Purpose: This was a prospective observational population pharmacokinetic study of nirmatrelvir/ritonavir (NIR/RIT) in critically ill adult patients and identify optimal dosing regimens.Patients and Methods: The prescription of NIR/RIT is determined by the attending physician and ranges from 150mg/100mg to 300mg/100mg twice a day. Two to three serial blood samples were collected for each patient after the second doses. We developed and validated PK model for plasma NIR and plasma RIT. Monte Carlo dosing simulations were performed to assess target attainment.Results: We analyzed 89 plasma samples from 31 adult patients. The data were best described by a one-compartment model. Among the covariates tested on pharmacokinetic parameters, creatinine clearance (CrCL) and area under curve (AUC) of RIT had a significant effect on apparent clearance (CL/F) of NIR. Mean (SD) parameters estimates for the absorption rate constant (Ka), apparent distribution (V/F) and CL/F were 0.42 (0.10) h− 1. 36.5 (8.5) L, 3.6 (0.26) L/h, respectively. Dosing simulations showed that the target in vitro 90% effective concentration (EC90) was more likely to be achieved twice a day than once a day at the same daily dose of NIR. High CrCL, low AUC of RIT were associated with a reduced likelihood of NIR reaching the target EC90.Conclusion: Based on our dosing simulations, the initial dosage of NIR/RIT was 300mg/100mg twice a day in critically ill patients with CrCL> 45 mL/min; When CrCL in critically ill patients is between 15 and 45 mL/min, NIR/RIT is 150mg/100mg twice a day. The maintenance dose is adjusted according to CrCL and AUC of RIT, with the dosages varying between 75mg/100mg and 300mg/100mg.Keywords: nirmatrelvir, ritonavir, pharmacokinetics, critically ill, creatinine clearance

Hua Liu,1,2,&ast; Yang-Min Hao,1,2,&ast; Sheng Jiang,1,2,&ast; Maiheliya Baihetiyaer,1,2 Cheng Li,3 Guo-Yao Sang,4 Zhiming Li,5 Guo-Li Du1,2,6 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Data Statistics and Analysis Center of Operation Management Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 4Laboratory Medicine Diagnostic Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 5Department of Ultrasound, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 6Bazhou People’s Hospital, Korla, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Li Du, Email genemagic@126.comPurpose: This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs).Methods: A case–control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated.Results: The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P< 0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index.Conclusion: SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.Keywords: MASLD, type 2 diabetes mellitus, sodium-glucose co-transporter-2 inhibitors, MACCEs, FIB-4 index

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

Naijing Li,1,&ast; Weiying Zhang,2,&ast; Siyuan Wu,3,&ast; Muhammad Shafiq,4 Peihan Xie,3 Lixiang Zhang,5 Shichao Jiang,3 Yue Bi1 1Department of Orthopedic Oncology, Yantai Shan Hospital, Yantai, People’s Republic of China; 2Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Innovation Center of Nanomedicines, Kawasaki Institute of Industrial Promotion, Kawasaki, Japan; 5Department of Health Management, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Bi; Shichao Jiang, Email dr_yuebi@126.com; mailjsc@163.comPurpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management.Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats.Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.).Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.Keywords: electrospinning, nanofiber membrane, wound healing, mesoporous silicon, strontium

Tao Zhu,1 Fang Kang,1 Ming-Ming Han,1 Fang He,2 Sen Jiang,2 Li-Na Hao,1 Xiang Huang,1 Juan Li1 1Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Electrophysiology, the First Affiliated Hospital of USTC, Division of life sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Juan Li, Department of anesthesiology, the First Affiliated Hospital of USTC, Division of life sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China, Email huamuzi1999@163.comPurpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM).Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes.Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7± 44.1 and 53.4± 35.4, respectively. Furthermore, the 95% confidence interval of the difference was − 25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P< 0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P< 0.05).Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.Keywords: anesthetics, abnormal muscle response, ciprofol, microvascular decompression

Siyuan Wang,1,&ast; Beiyao Gao,1,&ast; Minghui Shi,2– 6 Shiwei Qumu,2– 5 Fen Dong,2– 5,7 Peijian Wang,1 Ting Yang,2– 5 Shan Jiang1 1Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2National Center for Respiratory Medicine, Beijing, People’s Republic of China; 3National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 4Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 6Capital Medical University, Beijing, People’s Republic of China; 7Department of Clinical Research and Data management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shan Jiang; Ting Yang, China-Japan Friendship Hospital, 2 Yinghuayuan East St. Hepingli, Chaoyang District, Beijing, 100029, People’s Republic of China, Email landjiang@126.com; dryangting@qq.comObjective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD.Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study.Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was − 0.53 (− 0.95 to − 0.31) in non-EID group, − 0.20 (− 1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038).Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.Keywords: COPD, arterial stiffness, exercise-induced oxygen desaturation, rehabilitation

Sijie Jiang,1– 4 Shaobing Xie,1– 4 Zhihai Xie,1– 4 Weihong Jiang,1– 4 Hua Zhang1– 4 1Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Anatomy Laboratory of Division of Nose and Cranial Base, Clinical Anatomy Center of Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang; Hua Zhang, Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of China, Tel/Fax +86731-89753045, Email jiangwh68@126.com; entxy@126.comBackground: Elevated serum uric acid is crucial in the pathophysiology of chronic inflammatory diseases. However, its impact on chronic rhinosinusitis (CRS) recurrence risk is unknown. This study investigates the association between elevated serum uric acid and the risk of CRS recurrence.Methods: A retrospective cohort study was conducted on 1004 CRS patients (including 638 males and 366 females) who received functional endoscopic sinus surgery. All patients were followed up for more than 2 years, and categorized into subgroups based on phenotype, gender, and postoperative recurrence. Cox regression analysis was performed to evaluate the associations between serum uric acid and the risk of CRS recurrence.Results: After categorization, 104 males had hyperuricemia, and 54 females presented hyperuricemia. The rate of recurrent CRS in the hyperuricemia group was significantly higher compared to the non-hyperuricemia group in both males and females (P< 0.05). In both male and female patients, the rate of hyperuricemia and uric acid levels were elevated in the recurrent CRS group in comparison with the non-recurrent CRS group (P< 0.05). Unadjusted and adjusted Cox regression analysis demonstrated that serum uric acid was an independent risk factor for CRS recurrence (P< 0.05). The receiver operator characteristic curve showed that serum uric acid was a potential biomarker for predicting the recurrence of CRS and its phenotypes in both genders (P< 0.05).Conclusion: There is a close relationship between elevated serum uric acid and the recurrence risk of CRS and its phenotypes, suggesting that serum uric acid may be a novel biomarker for predicting recurrent CRS.Keywords: chronic rhinosinusitis, uric acid, hyperuricemia, biomarker, recurrence

Sifen Jiang,1,2,&ast; Tingyu Luo,2,&ast; Zhuoqi Zhu,3,&ast; Yanling Huang,2 Haopeng Liu,4 Bing Li,2 Suibin Feng,5 Kun Zeng1 1Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 2School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Guangxi, People’s Republic of China; 4School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suibin Feng, Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13430293807, Email 19526620667@163.com Kun Zeng, Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13790300213, Email Zengkun660524@163.comBackground: The treatment of Type 2 Diabetes Mellitus (T2DM) is a protracted and arduous process. Medication, being a universally crucial therapeutic measure, underscores the significance of medication adherence in managing the disease effectively. Medication beliefs have emerged as a significant predictor of adherence, attracting considerable scholarly attention in recent years. However, there remains a paucity of research utilizing individual-centered approaches to explore medication beliefs among the T2DM population during the hospital-home transition, leaving the relationship between these beliefs and medication adherence unclear.Purpose: To investigate latent categories of medication beliefs among patients with T2DM during the transition from hospital to home, and to analyze variations in medication adherence across these categories of patients.Patients and methods: Between August 2022 and September 2023, this study selected 304 patients with a pre-discharge diagnosis of T2DM as study subjects from a tertiary hospital in Dongguan City. The patients’ profiles were assessed comprehensively via the Sociodemographic and Clinical Characteristics Questionnaire, alongside the Chinese version of Beliefs about Medicines Questionnaire-Specific and Morisky Medication Adherence Scale-8. The present study conducted latent profile analysis using Mplus 7.4 software and analyzed the influencing factors of different medication belief categories and their differences in medication adherence using SPSS 26.0 software.Results: The medication beliefs of 304 patients were rated at 3.36± 5.24 points, while medication adherence scored 6.23± 1.56 points. The medication beliefs were classified into four categories: moderate necessity - low to moderate concern group (40.13%), high necessity - low concern group (9.54%), moderate necessity - moderate to high concern group (19.08%), and moderate necessity - high concern group (31.25%). Age, monthly per capita household income, and place of residence emerged as influential factors for the four categories. Moreover, the disparity in medication adherence among these categories demonstrated statistical significance (P < 0.001).Conclusion: The medication beliefs of patients were classified into four distinct categories, and variations in medication adherence were evident across these categories. The high necessity - low concern group demonstrated the highest medication adherence scores, while the moderate necessity - high concern group exhibited the lowest scores. Healthcare providers are advised to tailor personalized medication belief enhancement programs based on patients’ homogeneous beliefs, addressing specific issues encountered by each category. This approach aims to ensure optimal medication adherence across diverse medical and social environments, effectively improving patient prognosis and enhancing quality of life.Keywords: diabetes mellitus, T2DM, medication beliefs, medication adherence, latent profile analysis, influencing factors

Tianli Zheng,1,2 Weiwei Fu,1,2 Shuang Jiang,3 Xiaodong Yang1,2 1School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, Jiangsu, People’s Republic of China; 3The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaCorrespondence: Xiaodong Yang, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, No. 88, Keling Road, Suzhou, Jiangsu Province, 215000, People’s Republic of China, Email xiaodong.yang@sibet.ac.cnPurpose: The prevalence of obesity and myopia in young people is increasing worldwide; however, the association between body mass index (BMI) and myopia remains controversial. This study aimed to assess the association between BMI and myopia in Chinese schoolchildren.Patients and Methods: In this study, the open data for analysis were obtained from DATADRYAD website (www.datadryad.org). A total of 3658 children were enrolled in this study. Logistic regression model was used to analyze the relationship between BMI and myopia.Results: Compared with individuals with lower BMI Q1 (less than 25 kg/m2), the adjusted odds ratios (ORs) for BMI and myopia were 2.15 (95% confidence interval [CI]: 1.62– 2.86) in Q2 (25.0– 29.9 kg/m2) and 2.39 (95% CI: 1.37– 4.18) in Q3 (30.0 kg/m2 or more). Moreover, the association between BMI and myopia exhibited an inverted L-shaped curve (nonlinear; p < 0.001). When the BMI was < 25 kg/m2, an increased BMI was significantly associated with a higher risk of myopia (OR = 1.244 [95% CI: 1.211– 1.277], p < 0.001). However, when the BMI was ≥ 25 kg/m2, the association lost its significance (OR = 1.063 [95% Cl: 0.964– 1.171], p = 0.219).Conclusion: This study found an inverted L-shaped association between BMI and myopia in Chinese schoolchildren. A higher BMI was associated with a higher risk of myopia reaching 25 kg/m2, after which an increase in BMI was no longer associated with an increased risk of myopia.Keywords: myopia, body mass index, cross-sectional, schoolchildren, logistic regression

Bei Men, Yongjun Li, Shu Jiang Department of Prosthodontics and Implantation, Dazhong Stomatological Hospital, Wuhan, 430000, People’s Republic of ChinaCorrespondence: Bei Men, Department of Prosthodontics and Implantation, Dazhong Stomatological Hospital, Wuhan, 430000, People’s Republic of China, Email Bei_Meng@tom.comAbstract: Substantial evidence has recently been gathered to substantiate the epidemiological correlation between this oral inflammatory ailment and several systemic health disorders, such as cardiovascular diseases (CVDs). It is worth noting that certain shared factors exist among individuals with periodontal disease (PD) and CVDs, like obesity or overweight, minimal physical activities, smoking habits, male gender, low socioeconomic position, advanced age, and limited educational attainment. Moreover, recent research suggests a distinct and separate relationship between PD and CVDs. This literature review discusses the association between CVDs and PD and their underlying mechanisms and connections. Current literature strongly confirms a correlation between cardiovascular risk and PD. The underlying mechanisms involve inflammation, epigenetics, epithelial dysfunction, oral microbiome dysbiosis, and the efficacy of periodontitis treatment. Future investigations are required to comprehend these complex interactions and develop targeted interventions for oral health improvement and reduction in cardiovascular risk.Keywords: periodontal disease, cardiovascular disease, periodontitis, gingivitis, oral health, markers, inflammation

Qing-Qing Luo,&ast; Qiao-Nan Li,&ast; Dan Cai, Song Jiang, Shao-Song Liu, Mao-Sheng Liu, Cong Lv, Jin-Ke Wang, Kun-He Zhang, Ting Wang Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology & Hepatology, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Wang; Kun-He Zhang, Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Jiangxi Institute of Gastroenterology & Hepatology, No. 17, Yongwai Zheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86-13361659001 ; +86-13007202818, Email tingwang@ncu.edu.cn; khzhang@ncu.edu.cnPurpose: The differential diagnosis of atypical hepatocellular carcinoma (aHCC) and atypical benign focal hepatic lesions (aBFHL) usually depends on pathology. This study aimed to develop non-invasive approaches based on conventional blood indicators for the differential diagnosis of aHCC and aBFHL.Patients and Methods: Hospitalized patients with pathologically confirmed focal hepatic lesions and their clinical data were retrospectively collected, in which patients with HCC with serum alpha-fetoprotein (AFP) levels of ≤ 200 ng/mL and atypical imaging features were designated as the aHCC group (n = 224), and patients with benign focal hepatic lesions without typical imaging features were designated as the aBFHL group (n = 178). The performance of indexes (both previously reported and newly constructed) derived from conventional blood indicators by four mathematical operations in distinguishing aHCC and aBFHL was evaluated using the receiver operating characteristic (ROC) curve and diagnostic validity metrics.Results: Among ten previously reported derived indexes related to HCC, the index GPR, the ratio of γ-glutamyltransferase (GGT) to platelet (PLT), showed the best performance in distinguishing aHCC from aBFHL with the area under ROC curve (AUROC) of 0.853 (95% CI 0.814– 0.892), but the other indexes were of little value (AUROCs from 0.531 to 0.700). A new derived index, sAGP [(standardized AFP + standardized GGT)/standardized PLT], was developed and exhibited AUROCs of 0.905, 0.894, 0.891, 0.925, and 0.862 in differentiating overall, BCLC stage 0/A, TNM stage I, small, and AFP-negative aHCC from aBFHL, respectively.Conclusion: The sAGP index is an efficient, simple, and practical metric for the non-invasive differentiation of aHCC from aBFHL.Keywords: atypical hepatocellular carcinoma, differential diagnosis, conventional blood indicator, derived index, sAGP

Shuai Jiang,1,2 Man Xiong,3 Xinyi Rao,3 Jieting Liang,3 Xinghan Zhu,3 Hang Fu,1,2 Jiangyun Chen,3 Chengzeng Wang1,2 1The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Institute for Hospital Management of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3School of Health Management, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Chengzeng Wang; Jiangyun Chen, Email chengzengw@163.com; cjy112@i.smu.edu.cnPurpose: This study aims to investigate factors affecting medical personnel behavioral preferences for providing mHealth in China, so as to provide decision-making basis for mHealth providers and managers to encourage more doctors to participate in mHealth service delivery.Methods: Typical case sampling techniques were applied in a hospital setting to conduct a discrete choice experimental questionnaire survey of doctors (n=216) concerning mHealth preferences between July and October 2022. A conditional logit model was used to assess medical personnel preferences for each attribute and level of mHealth services.Results: Length of service, information security, subjects of treatment and financial compensation all have a significant effect on medical staff’s preference for providing mHealth services (p < 0.05). In terms of service duration and financial compensation, medical staff preferred mHealth services that provided shorter service duration and higher financial compensation; in terms of information security, medical staff preferred mHealth services with confidentiality of diagnostic and therapeutic information compared to information disclosure; and in terms of treatment targets, medical staff preferred the general population compared to key populations, such as pregnant women, the elderly, infants and children.Conclusion: The preference of medical professionals to provide mHealth services is affected by a variety of factors. By enhancing the confidentiality of information in mHealth services, providing more options for service recipients, increasing their financial compensation, and shortening the duration of the service or increasing the number of service hours that can be adjusted can guide improvement of mHealth services and promoting of its adoption among medical professionals.Keywords: doctor, mHealth, preferences, discrete choice experiment

Fang Wen,1,&ast; Shantong Jiang,1– 4,&ast; Ping Yuan,1– 5,&ast; Jinbo Liu,1– 4 Xiu Bai,1 Hongwei Zhao,1– 4,6,7 Xin Chen,1– 4,7 Yan-Bing Gong,5 Roland Asmar,8 Hongyu Wang1– 4,6,7 1Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 2Vascular Health Research Center of Peking University Health Science Center (VHRC-PKUHSC), Beijing, People’s Republic of China; 3Beijing Shijingshan District Key Clinical Specialty of Vascular Medicine, Beijing, People’s Republic of China; 4Heart and Vascular Health Research Center of Peking University Clinical Research Institute (HVHRC-PUCRI), Beijing, People’s Republic of China; 5Department of Scientific Research, Peking University Shougang Hospital, Beijing, People’s Republic of China; 6State Key Laboratory of Vascular Homeostasis and Remodeling, (Peking University), Beijing, People’s Republic of China; 7Heart and Vascular Health Research Center of Chengdu Medical College (HVHRC-CMC), Chengdu, People’s Republic of China; 8Foundation-Medical Research Institutes, Beirut, Lebanon&ast;These authors contributed equally to this workCorrespondence: Hongyu Wang, Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, 100144, People’s Republic of China, Email dr.hongyuwang@foxmail.comAbstract: Cardiovascular disease(CVD) has become a major disease burden affecting people’s health in China. Blood vessels are very important for human health and are the “sentinel” for the development of many cardiovascular and cerebrovascular diseases. The key to effectively preventing fatal, disabling heart, brain and peripheral vascular events lies in controlling traditional and non-traditional risk factors for vascular health from the source, and early assessment and intervention of early vascular lesions. Since 2004, China government promoted the early detection technology of vascular lesions and vascular medicine, and proposed the Beijing Vascular Health Stratification (BVHS) to provide suggestions for the examination, evaluation and management of risk factors, and to provide new ideas for lifelong maintenance of vascular health. This review mainly introduces the establishment and development of the clinical discipline of “vascular medicine” in the past 20 years in China, introduces the indicators for detecting vascular function and structure and the predictive value of vascular events, and carries out intelligent and digital management of vascular health throughout the life cycle of individualized prevention, treatment and rehabilitation for people with different parts or degrees of lesions, effectively reducing the occurrence and development of cardiovascular and cerebrovascular diseases, and the prospect of new technology in maintaining vascular health.Keywords: heart and vascular health, vascular medicine, early assessment, digital, Beijing vascular health stratification

Xiulin Huo,1,2 Peiying Huang,1 Hexuan Di,3 Tianxiao Ma,3 Sufang Jiang,1 Jie Yao,4 Lining Huang1 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Orthopaedic Surgery, The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of ChinaCorrespondence: Lining Huang, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email 15803213730@163.comPurpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees’ quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model.Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors.Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834.Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.Keywords: neuropathic pain, phantom limb pain, bone and soft tissue tumors, amputation, risk factors, prediction model

Guoying Qian,1,&ast; Yufeng Wu,2,&ast; Wei Wang,3 Ru Lei,4 Wanli Zhang,5 Suo Jiang,6,7 Yingying Huang,6 Zaiqing Zhang8 1College of Preschool Education, Capital Normal University, Beijing, 100048, People’s Republic of China; 2School of Psychology, Shaanxi Normal University, Xi’an, 330022, People’s Republic of China; 3Department of Psychology, Shanxi Datong University, Datong, 037009, People’s Republic of China; 4School of Education Science, Kaili University, Kaili, 556011, People’s Republic of China; 5School of Education Science, Shaanxi Xueqian Normal University, Xi’an, 710100, People’s Republic of China; 6Department of Applied Psychology in School of Psychiatry, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7The Affiliated Wenzhou Kangning Hospital of Wenzhou Medical University, Wenzhou, 32500, People’s Republic of China; 8Beijing Jacademy Consulting Co., LTD, Beijing, 101121, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Zaiqing Zhang, Beijing Jacademy Consulting Co., Ltd, Liyuan Dafang House, Tongzhou District, 330-1-2001, Beijing, 325035, People’s Republic of China, Email susanqy23@139.comPurpose: Chinese public mental health is currently characterized by a high prevalence of mental ill health and a low consultation rate, due primarily to the nation’s low mental health literacy. Previous studies have shown that occupational stress may be a risk factor for mental health literacy. In China, preschool teachers are under high pressure; however, few studies have examined the mechanisms that mediate and moderate the relationship between preschool teachers’ feelings of stress and their mental health literacy.Methods: A questionnaire was administered to 2352 preschool teachers to explore the relationship between their stress perceptions and mental health literacy.Results: Preschool teachers’ perceived stress was significantly and negatively associated with their mental health literacy, with anxiety playing a partially mediating role. Preschool teachers’ career resilience moderated the relationship between perceived stress and anxiety. Perceived stress positively predicted anxiety for teachers with low levels of career resilience; for teachers with high levels of career resilience, perceived stress still positively predicted anxiety, and the higher the level of career resilience, the weaker the positive prediction of stress perception on anxiety.Conclusion: Perceived stress directly predicted mental health literacy among preschool teachers, and also indirectly predicted mental health literacy through the mediating role of anxiety. Career resilience moderated the relationship between stress perception and anxiety. These findings provide new perspectives on the treatment and prevention of preschool teachers’ mental ill health.Keywords: mental health literacy, perceived stress, anxiety, career resilience, preschool teacher

Junzhuo Wang,1,&ast; Ying Tan,1,&ast; Yang Dai,2,3,&ast; Ke Hu,2 Xi Tan,1 Shaoli Jiang,4 Guannan Li,1 Xinlin Zhang,1 Lina Kang,1 Xiaojian Wang,4 Biao Xu1,2 1Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 4Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Xu, Department of Cardiology, the Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Email xubiao62@nju.edu.cn Xiaojian Wang, Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China, Email ias_xjwang@njtech.edu.cnPurpose: Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury.Methods: We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan’s Blue and Masson’s staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis.Results: The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced.Conclusion: We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.Graphical Abstract: Keywords: myocardial ischemia-reperfusion injury, extracellular vesicles, hydrogel, intranasal delivery, inflammation

Suling Jiang,1,&ast; Jian Wang,2,3,&ast; Zhiyi Zhang,4,&ast; Jie Zhan,1 Ruifei Xue,1 Yuanwang Qiu,5 Li Zhu,6 Shaoqiu Zhang,2 Yifan Pan,1 Xiaomin Yan,2 Yuxin Chen,3,7 Jie Li,1– 4 Xingxiang Liu,8 Chuanwu Zhu,6 Rui Huang,1– 4 Chao Wu1– 4 1Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 7Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email doctor_hr@126.comBackground: Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients.Methods: CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA).Results: A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727– 0.803) and 0.766 (95% CI: 0.711– 0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA.Conclusion: A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.Keywords: chronic hepatitis B, liver inflammation, prediction, nomogram, alanine aminotransferase

Sifen Jiang,1,&ast; Zhuoqi Zhu,2,&ast; Guisheng Liao,3,&ast; Yanling Huang,1 Lichang Li,4 Kun Zeng1 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Guangxi, People’s Republic of China; 3Emergency Outpatient, Dongguan Eighth People’s Hospital, Dongguan, People’s Republic of China; 4Endocrinology Department, Dongguan Eighth People’s Hospital, Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Zeng, School of Nursing, Guangdong Pharmaceutical University, No. 283, Jianghai Avenue, Haizhu District, Guangzhou City, Guangdong Province, 510310, People’s Republic of China, Tel +86 13790300213, Email Zengkun660524@163.comPurpose: To establish the relationship between medication literacy and medication beliefs among persons with type 2 diabetes mellitus (T2DM).Patients and methods: A cross-sectional survey of 246 patients with T2DM was conducted between April and November 2022 at a tertiary hospital in Dongguan City, Guangdong Province, China. Subsequently, these patients were administered the General Information Questionnaire, the Chinese version of Medication Literacy Assessment Scale, and the Chinese version of Beliefs about Medicines Questionnaire-Specific via survey.Results: The medication literacy score of patients with T2DM was 7.82± 3.007, and the medication beliefs score was 2.26± 4.011. The Pearson correlation analysis revealed a statistically significant but weakly positive correlation (r = 0.271, P < 0.001) between medication literacy and beliefs among patients diagnosed with T2DM. However, there was no significant correlation found between medication literacy and necessity (r = − 0.021, P > 0.05), while a lowly negative correlation was observed between medication literacy and concerns (r = − 0.307, P < 0.001). Moreover, the multiple linear regression analysis indicated that medication literacy, age, education level, and duration of medication usage were all significant factors influencing patients’ medication beliefs (all P < 0.05). Together, these variables accounted for 15.3% of the total variance observed in the regression equation.Conclusion: The study found a positive correlation between medication literacy and beliefs, and a negative correlation between medication literacy and concerns. These results indicate that enhancing medication literacy can improve medication adherence among individuals with T2DM by reducing concerns and strengthening medication beliefs.Keywords: type 2 diabetes mellitus, T2DM, medication literacy, medication beliefs, medication adherence, correlation

Guanglan Li,1,2 Jing Yu,1,2 Simin Jiang,1,2 Kefei Wu,1,2 Yiping Xu,1,2 Xiaohui Lu,1,2 Yating Wang,1,2 Jianxiong Lin,1,2 Xiao Yang,1,2 Zhibin Li,3 Haiping Mao1,2 1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; 2NHC Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China; 3Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, ChinaCorrespondence: Haiping Mao, Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China, Email maohp@mail.sysu.edu.cnPurpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD.Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan–Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities.Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088– 1.327, P< 0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126– 1.456, P< 0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066– 1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185– 2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only.Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.Keywords: all-cause mortality, cardiovascular mortality, peritoneal dialysis, systemic immune-inflammation index

Qi Meng,1,2,&ast; Jing Yang,1,2 Fei Wang,1,2 Cheng Li,3 Guoyao Sang,4 Hua Liu,1,2 Di Shen,1,2 Jinxia Zhang,1,2 Sheng Jiang,1,2,&ast; Aibibai Yusufu,1,2,&ast; Guoli Du1,2,&ast; 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Laboratory Medicine Diagnostic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Data Statistics and Analysis Center of Operation Management Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoli Du; Aibibai Yusufu, Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, People’s Republic of China, Email genemagic@126.com; hebibe@163.comPurpose: Cardiovascular disease is the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to develop and validate a nomogram for predicting the risk factors for coronary heart disease (CHD) in T2DM in the population of northwestern China.Patients and Methods: The records of 2357 T2DM patients who were treated in the First Affiliated Hospital of Xinjiang Medical University from July 2021 to July 2022 were reviewed. After some data (n =239) were excluded, 2118 participants were included in the study and randomly divided into a training set (n =1483) and a validation set (n = 635) at a ratio of 3:1. Univariate and stepwise regression analysis was performed to screen risk factors and develop predictive models. The results of logistic regression are presented through a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were employed to verify the distinction, calibration, and clinical practicality of the model.Results: The stepwise logistic regression analysis suggested that independent factors in patients with T2DM combined with CHD were age, gender, hypertension (HTN), glycated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and Uygur, which were associated with the occurrence of CHD. The nomogram demonstrated good discrimination with a C-index of 0.771 (95% CI, 0.741, 0.800) in the training set and 0.785 (95% CI, 0.743, 0.828) in the validation set. The area under curve (AUC) of the ROC curves were 0.771 (95% CI, 0.741, 0.800) and 0.785 (95% CI, 0.743, 0.828) in the training and validation sets, respectively. The nomogram was well-calibrated. The DCA revealed that the nomogram was clinically valuable.Conclusion: A nomogram based on 7 clinical characteristics was developed to predict CHD in patients with T2DM.Keywords: nomogram, coronary heart disease, type 2 diabetes mellitus, ethnicity, risk factor

Jiayi Li,1,2 Jiao Zhang,2 Xu Wang,2 Xumin Zheng,2 Hongmei Gao,2 Shimin Jiang,2 Wenge Li1,2 1Department of Nephrology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wenge Li, Department of Nephrology, China-Japan Friendship Hospital, No. 2, Yinghua Dong Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email wenge_lee2002@126.comIntroduction: Complement activation is highly involved in membranous nephropathy. Identifying the mechanism of the complement activation pathway carries crucial therapeutic implications yet remains controversial. This study explored lectin complement pathway activation in PLA2R-associated membranous nephropathy (MN).Methods: One hundred and seventy-six patients with biopsy-proven PLA2R-associated MN were enrolled in the retrospective study and divided into the remission group (24-hour urine protein < 0.75g and serum albumin > 35 g/L) and the nephrotic syndrome group. The clinical manifestation and C3, C4d, C1q, MBL, and B factor in renal biopsy tissues and C3, C4, and immunoglobulins in serum were evaluated.Results: Deposition of glomerular C3, C4d, and mannose-binding lectin (MBL) was significantly higher in the activated state than in the remission state in PLA2R-associated MN. MBL deposition was the risk factor for no remission. During follow-up, the persistent non-remission patients have significantly lower serum C3 levels.Conclusion: Activation of the lectin complement pathway in PLA2R-associated MN may contribute to proteinuria progression and disease activity.Keywords: membranous nephropathy, anti-PLA2R antibody, complement, lectin pathway

Shan Jiang,1,2 Zhaolei Cui,3 Jianfeng Zheng,1 Qiaoling Wu,1 Haijuan Yu,1 Yiqing You,3 Chaoqiang Zheng,3 Yang Sun1 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of China; 2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 3Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of ChinaCorrespondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Email sunyang@fjzlhospital.comBackground: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body’s adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors.Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated.Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group.Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.Keywords: ICD, cervical cancer, immunity, prognosis, immunotherapy response

Zhaolin Li,1,&ast; Qiaojun Zeng,1,&ast; Shuwan Xu,2,&ast; Yuewei Li,1 Tiantian Tang,1 Jianting Shi,1 Xueming Song,1 Wenman He,1 Liang Chen,1 Guirong Liu,1 Boying Gao,3 Jianming Zheng,4 Linjie Huang,1 Ming Chen,1 Shanping Jiang1 1Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Cardiovascular Medicine Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanping Jiang; Ming Chen, Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yan-jiang Xi Road 107, Guangzhou, 510120, People’s Republic of China, Tel +86-20-81332441, Email jiangshp@mail.sysu.edu.cn; chenm69@mail.sysu.edu.cnBackground: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy.Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by > 10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for > 3 s than the ULN or reduced serum level of fibrinogen to < 2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed.Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732– 0.851) and 0.730 (0.629– 0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy.Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.Keywords: tigecycline, drug-resistant bacteria, coagulopathy, nomogram

Kaili Li, Sanle Jiang, Hongxue Fu, Yingting Hao, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Emergency Department, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, 17th Floor, Building 1, Chongqing, People’s Republic of China, Tel +86 023-89011756, Email doctortianshijing@163.com; cyzfc1966@126.com; zfc88@126.comBackground: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis.Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis.Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11– 45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11– 35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475– 17.595, P=0.01) by Cox proportional-hazards regression.Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.Keywords: CRO, acute cholangitis, risk factors, prognosis

Xiufang Wang,1,&ast; Jia Liu,1,&ast; Andong He,1 Zhiyong Dong,2– 4 Xiaomei Chen,2– 4 Shuqing Yu,2– 4 Lilian Gao,2– 4 Huaxi Wang,2– 4 Wenhui Chen,2– 4 Ruixiang Hu,2– 4 Shuwen Jiang,2– 4 Jianxue Wang,2– 4 Yuan Chen,2– 4 Cunchuan Wang,2– 4 Wah Yang,2– 4 Ruiman Li1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Jinan University Institute of Obesity and Metabolic Disorders, Guangzhou, People’s Republic of China; 4Guangdong-Hong Kong-Macao Joint University Laboratory of Metabolic and Molecular Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruiman Li, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Avenue West, Guangzhou, People’s Republic of China, Email hqyyck@126.com Wah Yang, Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Avenue West, Guangzhou, People’s Republic of China, Email yangwah@qq.com; yangwah@connect.hku.hkBackground: Bariatric and metabolic surgery (BMS) is an effective treatment for obesity and its complications, but its effect on pregnancy outcomes is inconclusive. The present study aimed to investigate women’s pregnancy status and outcomes as well as the impact of pregnancy intervals after BMS.Methods: The menstrual cycle and fertility status of women who underwent BMS in our centre between July 2010 and January 2021 were retrospectively analyzed and followed up until one-year post-delivery. The pregnancy outcomes after BMS were observed, including changes in weight, pregnancy interval, pregnancy complications, weight and health status of the newborn (premature birth, admission to neonatology, or deformity).Results: We identified 31 women who were successfully conceived after BMS. There were statistical differences in weight and menstrual status before and post-operation (P < 0.05), and 77.97% of them had remission or recovery of obesity-related comorbidities. Eighteen patients delivered successfully after BMS, but there were still 12 cases of spontaneous abortion and 1 case of induced abortion. The abortion rate in pregnancy intervals less than 2 years was higher than those ≥ 2 years (P = 0.045). Of the women who delivered successfully, 5 had pregnancy-specific complications, including gestational diabetes mellitus and hypertensive disorder of pregnancy. However, the growth and development of the newborn are normal since the birth follow-up.Conclusion: The present results suggest that the abortion rate in pregnancy intervals less than 2 years was higher than those ≥ 2 years. It is recommended that postoperative patients avoid pregnancy until their weight is stable to reduce the risk of adverse pregnancy outcomes.Keywords: pregnancy, bariatric surgery, metabolic surgery, obesity

Jiao Song,&ast; Huixia Ye,&ast; Senwei Jiang, Yuebo Yang, Xiaomao Li Gynaecology Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuebo Yang; Xiaomao Li, Gynaecology Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China, Tel/Fax +86 20-85252259 ; +86 20-85253289, Email yangyueb@mail.sysu.edu.cn; Lixmao@mail.sysu.edu.cnIntroduction: Complete resection of all visible disease (R0 resection) is critical for the treatment of ovarian cancer patients, and accurate real-time guidance provided by intraoperative near-infrared (NIR) fluorescence images is beneficial for achieving complete resection of all visible disease.Methods: Based on the optical properties of IR780 and the characteristics of the acidic tumor microenvironment, we develop a new smart nanoparticle (eg, FA-IR780&PFOB-SNPs) by using the pH response nano framework (FA-PEG-PLGA-PEOz) and adjusting the amount of IR780. The FA-IR780&PFOB-SNPs was characterized for morphology, microstructure, particle size, pH-response, drug-loading efficiency and biological safety. The ultraclear fluorescence Navigation Endoscopy System was applied to evaluate the tumor recognition of FA-IR780&PFOB-SNPs in vivo.Results: The structure of FA-IR780&PFOB-SNPs was stable in a neutral environment, and the near-infrared (NIR) fluorescence was turned off, while the structure of FA-IR780&PFOB-SNPs was degraded in the acidic tumour microenvironment, and the NIR fluorescence was turned on. Through the ovarian subcutaneous xenograft tumour and ovarian intraperitoneal xenograft tumour models, it was confirmed that FA-IR780&PFOB-SNPs could clearly display the boundaries of abdominal micron-sized tumours through near-infrared fluorescence imaging, with a TBR greater than 5.Conclusion: The FA-IR780&PFOB-SNPs have the potential to provide to ovarian cancer intraoperative near infrared fluorescence navigation during precision tumour resection to achieve R0 and improve the prognosis of ovarian cancer patients.Keywords: near-infrared fluorescence imaging, IR780 iodide, epithelial ovarian cancer, tumour-activatable nanoparticles

Sijie Jiang,1– 3 Shaobing Xie,1– 3 Ruohao Fan,1– 3 Qingping Tang,4 Hua Zhang,1– 3 Fengjun Wang,1– 3 Shumin Xie,1– 3 Kelei Gao,1– 3 Junyi Zhang,1– 3 Zhihai Xie,1– 3 Weihong Jiang1– 3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8975-3045, Email jiangwh68@126.comPurpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR.Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children.Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P< 0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785).Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.Keywords: allergic rhinitis, subcutaneous immunotherapy, miRNA, exosome, children

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Yuanyuan Jiang,1 Shan Jiang,1,2 Qing Long,1 Jundi Yang,1,3 Jyu-Lin Chen,4 Jia Guo1 1Xiangya School of Nursing, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3School of Nursing, The University of Hong Kong, Hong Kong, People’s Republic of China; 4School of Nursing, University of California San Francisco, San Francisco, CA, USACorrespondence: Jia Guo, Tel +86 13875947418, Email guojia621@163.comBackground: Women in rural areas of China face the unique risk of developing diabetes, but data on the glycemic status among women without prior diabetes diagnosis in rural areas are lacking which may limit the decision-making for diabetes screening or prevention. This study was aimed to describe the glycemic status of women determined by hemoglobin A1c (HbA1c) and explore its associating factors.Methods: A cross-sectional survey was conducted among women without prior diabetes diagnosis from two counties of rural areas in Central South China from July to October 2018. On the basis of the life course framework, data on socio-demographic, environmental health, genetic, biological (blood pressure, weight and height, lipids), psychosocial, and healthy behavioral factors were collected on site either through questionnaires or field measurements. The questionnaires included social-demographic sheet, Perceived Stress Scale, Self-efficacy scales for health-related diet and exercise behaviors, and Chinese Diabetes Risk Questionnaire. Generalized linear model analysis was performed to determine the associating factors of glycemic status, which was measured by HbA1c level.Results: A total of 647 women were included in the study. The median age of women was 51.00 years (range 35– 65 years). The median HbA1c level was 5.1% (interquartile range 4.6%-5.5%, range 4– 13.6%), and 8.7% (n=56) of women were identified as elevated glycemic status (HbA1c> 6%). Environmental health factors (eg, living in less-developed county [β=0.206, p=0.027]), biological factors (eg, higher body mass index [β=0.201, p=0.036], higher total cholesterol [β=0.097, p=0.040], history of gestational diabetes mellitus [β=0.722, p< 0.001]), and psychosocial factors (eg, higher perceived stress [β=0.247, p=0.002]) were associated with higher HbA1c level.Conclusion: This study reported 8.7% of elevated glycemic status among women without prior diabetes diagnosis in rural Hunan Province, China. After a comprehensive investigation based on a theoretical framework, living in a less-developed county of rural areas, having larger body mass index, higher total cholesterol, higher perceived stress, and a gestational diabetes mellitus history were identified as associating factors of higher HbA1c level. Professional support regarding weight control, blood lipid control, stress management, and the prevention of gestational diabetes mellitus should be recommended among this population, especially for women from less-developed counties.Keywords: women, rural areas, glycemic status, hemoglobin A1c, associating factors, survey

Li Shao,1 Sujing Jiang,1 Yan Li,2 Yanqin Shi,1,3 Man Wang,4 Ting Liu,1 Suzhen Yang,2 Laiji Ma1,3 1School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 2R&D Innovation Center, Shandong Freda Biotech Co., Ltd, Jinan, Shandong, People’s Republic of China; 3The Oriental Beauty Valley Research Institute, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 4Department of Nutrition, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, People’s Republic of ChinaCorrespondence: Laiji Ma, School of Perfume and Aroma Technology, Shanghai Institute of Technology, No. 100, Haiquan Road, Fengxian District, Shanghai, 201418, People’s Republic of China, Email laijima_sh@163.com Suzhen Yang, R&D Innovation Center, Shandong Freda Biotech Co., Ltd, No. 888, Xinluo Street, Lixia District, Jinan, Shandong, 250101, People’s Republic of China, Email 85844202@qq.comBackground: Late bedtime is a common form of unhealthy sleep pattern in adulthood, which influences circadian rhythm, and negatively affects health. However, little is known about the effect of regular late bedtime on skin characteristics, particularly on skin microbiome.Objective: To investigate the changes and effects of the regular late bedtime on skin physiological parameters and facial bacterial microbiome of 219 cases of Chinese women aged 18– 38 years living in Shanghai.Methods: Based on the Self-Evaluation Questionnaire, bedtime was categorized as 11:00 PM; thus, the volunteers were divided into early bedtime group (S0) and late bedtime group (S1). The physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiome was analyzed by 16S rRNA high-throughput sequencing.Results: The skin physiological parameters of the late bedtime group exhibited significant decrease in skin hydration content, skin firmness (F4) and elasticity (R2), while TEWL, sebum and wrinkle significantly increased. The result indicated that late bedtime significantly impaired the integrity of skin barrier, damaged skin structure, and disrupted water–oil balance. Furthermore, the analysis of α-diversity, Sobs, Ace and Chao index were found to significantly decrease (P < 0.05) in the late bedtime group, suggesting that late bedtime reduced both the abundance and the diversity of facial bacterial microbiota. Moreover, the abundance of Pseudomonas increased significantly, while Streptococcus, Stenotrophomonas, Acinetobacter, Haemophilus, Actinomyces and Neisseria decreased significantly. In addition, Spearman correlation analysis revealed strong correlations between the microbiota and the physiological parameters. Notably, the abundance of Pseudomonas significantly positively correlated with skin firmness and elasticity, but significantly negatively correlated with skin hemoglobin content, melanin content and skin hydration.Conclusion: Bedtime is an important factor in maintaining skin health. Regular late bedtime not only damages the skin barrier and skin structure but also reduces the diversity and composition of facial bacterial microbiome.Keywords: sleep, late bedtime, skin biophysical property, skin barrier, skin microbiota

Jing Yang,&ast; Sheng Jiang&ast; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia; Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng Jiang, Email xjjiangsheng@126.comPurpose: To develop a nomogram model that predicts the risk of diabetic nephropathy (DN) incidence in type 2 diabetes mellitus (T2DM) patients.Methods: We collect information from electronic medical record systems. The data were split into a training set (n=521) containing 73.8% of patients and a validation set (n=185) holding the remaining 26.2% of patients based on the date of data collection. Stepwise and multivariable logistic regression analyses were used to screen out DN risk factors. A predictive model including selected risk factors was developed by logistic regression analysis. The results of binary logistic regression are presented through forest plots and nomogram. Lastly, the c-index, calibration plots, and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram in internal and external validation. The clinical benefit of the model was evaluated by decision curve analysis.Results: Predictors included serum creatinine (Scr), hypertension, glycosylated hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), body mass index (BMI), triglycerides (TG), and Diabetic peripheral neuropathy (DPN). Harrell’s C-indexes were 0.773 (95% CI:0.726– 0.821) and 0.758 (95% CI:0.679– 0.837) in the training and validation sets, respectively. Decision curve analysis (DCA) demonstrated that the novel nomogram was clinically valuable.Conclusion: Our simple nomogram with seven factors may help clinicians predict the risk of DN incidence in patients with T2DM.Keywords: type 2 diabetes mellitus, diabetic nephropathy, nomogram, risk factors

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Linyan Huang1 &ast;, Li Zhang1,2 &ast;, Shuiping Jiang,1 Baozhu Liang,1 Ningning Xu,1 Jingxin Li,1 Xiaoyan Zhang,1,3 Zhen Zhang1 1Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, People’s Hospital of Dehong, Yunnan, People’s Republic of China; 3Department of Pediatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Zhen Zhang, Department of Endocrinology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong, 510282, People’s Republic of China, Tel +86-15913162742, Email zzhen311@163.comBackground: The coronavirus disease 2019 (COVID-19) outbreak has seriously affected people’s lives, especially those with chronic diseases. Diabetes self-management, which plays an important role in glycaemic control and reducing the risk of acute and long-term complications, may be discouraged by social distancing.Purpose: To evaluate the level of self-management activities in Chinese patients with type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic.Patients and Methods: A survey of with 872 patients with T2DM in the inpatient and outpatient departments through face-to-face interviews was conducted from 1 July, 2020 to 30 September, 2020. The main outcome measures were glycaemic control status and level of self-management activities during the pandemic.Results: In terms of glycaemic control, the data showed that patients with fasting plasma glucose (FPG) < 7.0 mmol/L (36.4%), postprandial plasma glucose (PPG) < 10.0 mmol/L (26.3%), or glycosylated haemoglobin (HbA1c) < 7.0% (18.6%) in our investigation has well-controlled blood glucose level, and 11.9% of patients experienced blood glucose < 3.9 mmol/L during the outbreak. The diabetes self-management of Chinese patients decreased and the final diabetes self-management score of the Chinese patients was 3.4 ± 1.45. Patients with higher education, diabetes education, comorbidities, and online consultations had higher diabetes self-management scores (P < 0.05). Adherence to diabetes self-management in the normal glycaemic control group was higher than that in the substandard glycaemic control group (P< 0.05). Among all participants, 72.1% of the patients reduced the frequency of hospital visits, and 44.8% considered that they had diabetes-related stress during the pandemic. The mean anxiety level score rated by 286 patients was 5.3± 2.8.Conclusion: The COVID-19 pandemic has affected diabetes self-management, including substandard glycemic control, increased diabetes-related stress, limited exercise range and medical visits. Therefore, future interventions should focus on the online management of chronic diseases and support online consultation’ development and promotion, which can overcome physical distance and provide personalized services conveniently.Keywords: coronavirus disease 2019, diabetes self-management, online consultation, type 2 diabetes mellitus

Shutian Jiang,&ast; Wenzhi Li,&ast; Xinxi Zhao, Li Chen, Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanping Kuang; Wenzhi Li, Email kuangyp1506@sh9hospital.org.cn; liwzx@126.comPurpose: Ovarian hyperstimulation syndrome (OHSS) is a serious complication of controlled ovarian hyperstimulation. In this study, we hope to explore whether nintedanib, a tyrosine kinase inhibitor, can inhibit OHSS by blocking signaling of vascular endothelial growth factor in a mouse model. Considering that nintedanib been approved for the treatment of some diseases. We believe that nintedanib has important potential in the treatment of OHSS.Methods: Female ICR mice aged 6– 8 weeks with similar initial weights were used to establish the OHSS model. At 12 and 24 hours after human chorionic gonadotropin (hCG) trigger, we administered nintedanib by subcutaneous injection and analyzed the OHSS-related physiological characteristics and biochemical indices of the model mice within 48 hours after hCG-trigger.Results: Nintedanib significantly alleviated the symptoms of OHSS after hCG-trigger compared with those of OHSS group (weight change, P < 0.0001; ovarian weight, P < 0.0001, peritoneal exudation level, P < 0.01). Further investigation proved that the corpus luteum (number, P < 0.001; diameter, P < 0.0001) and luteal vessel (P < 0.0001) development were inhibited in the nintedanib administration group. Then, the vascular permeability test showed that the capillary bleeding points (P < 0.0001) were also significantly reduced in nintedanib administration group. Gene expression tests demonstrated that the intercellular connection-related genes expression in the nintedanib administration group was similar to that in the no-OHSS induced group. Further detection of coagulation and thrombosis indices indicated that the nintedanib administration in the OHSS model did not increase the risk of thrombosis or bleeding.Conclusion: Our study demonstrated that nintedanib can alleviate and manage the symptoms of OHSS in a mouse model. These findings identify a feasible scheme for the prevention and treatment of OHSS in clinical practice in the future. Moreover, since the scheme can be implemented after ovulation, it will not cause potential adverse effects on gametogenesis, fertilization or embryonic development.Keywords: ovarian hyperstimulation syndrome, vascular endothelial growth factor, nintedanib, tyrosine kinase inhibitor, vascular permeability

Shengjie Jiang,1 Xiuhui Wang,2 Yuhan Ma,3 Yuning Zhou,4 Lu Liu,5 Fei Yu,5 Bing Fang,5 Kaili Lin,1 Lunguo Xia,5 Ming Cai1 1Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China; 3Department of Stomatology, Medical college of Soochow University, Jiangsu, People’s Republic of China; 4Department of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 5Department of Orthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Lunguo Xia, Department of Orthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Huangpu District, Shanghai, People’s Republic of China, Tel +86 13761955106, Fax +86-21-63136856, Email xialunguo@hotmail.com Ming Cai, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Huangpu District, Shanghai, People’s Republic of China, Tel +86 13918490900, Fax +86-21-63136856, Email zidanecm500@126.comBackground: The synergistic effect of chemical element doping and surface modification is considered a novel way to regulate cell biological responses and improve the osteoinductive ability of biomaterials.Methods: Hydroxyapatite (HAp) bioceramics with micro-nano-hybrid (a mixture of microrods and nanorods) surfaces and different strontium (Sr) doping contents of 2.5, 5, 10, and 20% (Srx-mnHAp, x: 2.5, 5, 10 and 20%) were prepared via a hydrothermal transformation method. The effect of Srx-mnHAp on osteogenesis and angiogenesis of bone marrow stromal cells (BMSCs) was evaluated in vitro, and the bioceramics scaffolds were further implanted into rat calvarial defects for the observation of bone regeneration in vivo.Results: HAp bioceramics with micro-nano-hybrid surfaces (mnHAp) could facilitate cell spreading, proliferation ability, ALP activity, and gene expression of osteogenic and angiogenic factors, including COL1, BSP, BMP-2, OPN, VEGF, and ANG-1. More importantly, Srx-mnHAp (x: 2.5, 5, 10 and 20%) further promoted cellular osteogenic activity, and Sr10-mnHAp possessed the best stimulatory effect. The results of calvarial defects revealed that Sr10-mnHAp could promote more bone and blood vessel regeneration, with mnHAp and HAp bioceramics (dense and flat surfaces) as compared.Conclusion: The present study suggests that HAp bioceramics with micro-nano-hybrid surface and Sr doping had synergistic promotion effects on bone regeneration, which can be a promising material for bone defect repair.Keywords: bioceramics, scaffolds, surface modification, element doping, bone regeneration

Shan Jiang,1,&ast; Yong-Qiang Wang,2,&ast; Yifei Tang,1 Xi Lu,1 Dan Guo1 1Department of Rehabilitation Medicine, the China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2Department of Ophthalmology, the Sunshine Union Hospital, Weifang, Shandong, 261071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shan JiangDepartment of Rehabilitation Medicine, the China-Japan Friendship Hospital, No. 2 Ying Hua Yuan East Street, Beijing, 100029, People’s Republic of China, Tel +86 10 84205288, Fax +86 10 64217749, Email landjiang@126.comBackground: As a severe complication of sepsis, sepsis-associated encephalopathy (SAE) usually manifests as impaired learning and memory ability in survivors. Previous studies have reported that environmental enrichment (EE) can increase the learning and memory ability in different brain injury models. However, there has been no research on the possible positive effect of EE on SAE.Aim: The present study aimed to test the effect of EE on SAE-induced impairment of learning and memory and its related mechanisms.Methods: A Morris water maze test (MWM) was used to evaluate the learning and memory ability of SAE rats that received EE housing or not. The expression of vasopressin (VP) was assessed using immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISAs). The synthesis of VP in the supraoptic nucleus (SON) was determined using quantitative real-time reverse transcription-PCR analysis. Moreover, inflammatory markers and brain-derived neurotrophic factor (BDNF) were detected using ELISA.Results: The results showed that SAE induced a decreased learning and memory ability, while EE reversed this impairment. EE also enhanced the synthesis and secretion of VP in the SON. Blocking the action of VP in the hippocampus interrupted the EE-induced amelioration of learning and memory impairment. Moreover, EE induced changes to the levels of BDNF and cytokines in the hippocampus and these effects were mediated by VP binding to the VP receptor 1a.Conclusion: Our findings demonstrated that the enhanced synthesis and secretion of VP in the SON are a key determinant responsible for EE-induced alleviation of learning and memory deficits caused by SAE.Keywords: sepsis associated encephalopathy, environmental enrichment, vasopressin, learning and memory, vasopressin receptor 1a

Yingying Huang,1,&ast; Shaowei Jiang,1,&ast; Wenjie Li,1 Yiwen Fan,2 Yuxin Leng,3 Chengjin Gao1 1Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology Medicine Biology, The University Medical Center Groningen, Groningen, the Netherlands; 3Critical Care Medicine Department, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao; Yuxin Leng Email gaochengjin@xinhuamed.com.cn; lengyx@bjmu.edu.cnBackground: A modified scoring system based on the RDW, AGE, SOFA, and APACHE II score (RAAS score) was composed to investigated the short-, medium-, and long-term high risk of mortality in patients with sepsis identified early in the emergency department (ED).Methods: Data were collected from a total of 1066 sepsis patients in emergency department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from March 2013 to April 2021, including 529 patients in the primary cohort and 537 patients in the validation cohort. By comparing each parameter and the area under ROC (AUC) and K-M (Kaplan–Meier) survival curve in different periods, valuable parameters were screened out to form a new scoring system, and finally the prediction model of the nomogram was built.Results: The RAAS scoring system, consisting of RDW, AGE, SOFA and APACHE II, is a 0– 6 scale to reflect the severity of sepsis. AUC at 30, 60, and 90 days was 0.816, 0.815, and 0.820, respectively. K-M curves across six prognostic time periods in both databases showed survival probabilities with different RDW segments and RAAS scores. In the calibration curve, the results of the internal validation of the primary cohort and the results of the external validation cohort showed the prognostic accuracy of RAAS.Conclusion: The RAAS score system is a novel and reliable indicator to predict the short-term and medium-term mortality of patients with sepsis. With the increase of the RAAS score, the mortality of patients with sepsis gradually increases.Keywords: sepsis, risk factors, prognosis, mortality, nomograms

Shiyu Jiang, Jixiang Xu, Xia Xiong, Yongqiong Deng Department of Dermatology & STD, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Yongqiong DengDepartment of Dermatology & STD, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan Province, People’s Republic of ChinaTel +86-13679670608Fax +86-8303165651Email dengyongqiong1@126.comAbstract: The common causes for melanonychia include melanoma, repetitive trauma, underlying systemic diseases, onychomycosis, pseudomonas infection and drugs. Drug-induced melanonychia usually affects numerous nails and appears as light brown to black pigmentation on the deck or nail bed with longitudinal, transverse or diffuse distribution. In previous cases, a number of chemotherapeutic agents such as azathioprine, bleomycin sulfate, cyclophosphamide, hydroxyurea and methotrexate were usually linked to melanonychia. Citri reticulatae pericarpium (CRP) is a traditional Chinese herb which is widely used in many foods and health care products in China. Up till now, there were no adverse reactions of CRP reported throughout the literature. Herein, we firstly reported a case of melanonychia in a 67-year-old man caused by CRP for external use.Keywords: traditional Chinese herb, citri reticulatae pericarpium, melanonychia

Shaowei Jiang,1 Jing Ma,2 Shan Ye,3 Connor Meaney,4 Timothy Evan Moore,4 Shuming Pan,1 Chengjin Gao1 1Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Internal Medicine, Shanghai Songnan Community Health Service Center, Shanghai, 200092, People’s Republic of China; 4Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USACorrespondence: Chengjin Gao; Shuming Pan Email gaochengjin@xinhuamed.com.cn; panshuming@xinhuamed.com.cnObjectives(s): Toll-like receptors (TLRs) on platelets have been extensively studied. Both TLR2 and TLR4 have been shown to augment platelet activation and alter its function from a hemostatic regulator to an immune sentinel. However, few studies have investigated the relationship between genetic polymorphisms in TLR2, TLR4 and platelets. We investigated whether genetic polymorphisms of TLR2 and TLR4 were related to thrombocytopenia and coagulation failure in Chinese patients with sepsis.Basic Methods: Adult Chinese patients with sepsis in the intensive care unit of a university medical center were monitored for up to 28 days. Thrombocytopenia and disseminated intravascular coagulation (DIC), diagnosed using Japanese Association for Acute Medicine (JAAM) criteria, were observed as the primary outcomes. Single-nucleotide polymorphisms (SNPs) in TLR2 (rs111200466, rs5743708) and TLR4 (rs11536889, rs145801336, rs11536896, rs7869402) in patients with sepsis were detected by polymerase chain reaction. The data were analyzed using chi-square and rank sum tests.Results: The genotype of TLR2 (rs111200466) (Del/Del) was associated with the initial DIC. The genotype of TLR4 (rs11536889) (C/C&C/G) was associated with initial DIC, DIC onset during hospitalization and platelet counts. Furthermore, both DIC and platelet counts were associated with cytokines and chemokines, especially the IL10.Conclusion: Our results demonstrate that in Chinese sepsis patients, the rs111200466 SNP in TLR2 and rs11536889 SNP in TLR4 are associated with thrombocytopenia and DIC, with potential effects on the TLR4 pathways of platelets.Keywords: sepsis, disseminated intravascular coagulation, TLR2/4, genetic polymorphisms