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Cheng-Jie Mao,1,* Hao Peng,2,* Sheng Zhuang,1,* Ying-Chun Zhang,3 Wei-Ye Xie,1 Jia-Hui Yan,1 Hui-Hui Liu,1 Jing Chen,1 Jun-Yi Liu,4 Jianan Zhang,5 Hai Jiang,5 Yonghong Zhang,2 Mingzhi Zhang,2 Chun-Feng Liu1,6 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 4Department of Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Chronic Disease, Taicang Center of Disease Prevention and Control, Suzhou, People’s Republic of China; 6Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Feng Liu, Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email liuchunfeng@suda.edu.cn Mingzhi Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of China, Email zhangmingzhi@suda.edu.cnBackground: Sleep is critical in health problems including Parkinson’s disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD.Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension.Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (β = 0.02, 95% CI: 0.01– 0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02– 1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01– 0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04– 1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD.Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.Keywords: prodromal Parkinson’s disease, sleep, Parkinson’s disease

Bo-Ran Deng,1,&ast; Yang Zhang,2,&ast; Zi-Feng Xie,3,&ast; Ding-Ding Wang,4,&ast; Tao Zeng,1 Dong-Bo Zhang,3 Li Huang,1 Qi-Yan Wang,1 Tu Shen,3 Qiao-Ling Wu3 1Surgical Anesthesia Center, Zigong Hospital of TCM, Zigong, 643000, People’s Republic of China; 2Department of Anesthesia, Da’an District Maternal and Child Health Hospital, Zigong, 643000, People’s Republic of China; 3Department of Anesthesia, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 4Department of Anesthesia, EYE & ENT Hospital of Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tu Shen; Qiao-Ling Wu, Department of Anesthesia, the First Affiliated Hospital of Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou, 121000, People’s Republic of China, Email shentu2011@sina.com; wqiaoling2013@sina.comPurpose: The debate continues over the differential impact of remimazolam vs propofol on hemodynamic stability. This study aims to elucidate the effects of a combination of remimazolam and esketamine vs propofol and esketamine on hemodynamic parameters in elderly patients undergoing painless colonoscopies.Patients and Methods: We conducted a randomized controlled trial involving 754 patients, divided equally between two treatment groups. The remimazolam-esketamine group (RE group) received 0.15 mg/kg of remimazolam and 0.3 mg/kg of esketamine. Conversely, the propofol-esketamine group (PE group) was administered 1.5 mg/kg of propofol with 0.3 mg/kg of esketamine. Primary outcomes focused on the incidence of hypotension. Secondary outcomes assessed were other hemodynamic adverse events, intraoperative blood pressure and heart rate fluctuations, usage of vasoactive agents, sedation efficacy, and additional adverse reactions.Results: Hypotension occurred significantly less frequently in the RE group (9.78%, 95% confidence interval[CI]: 6.67– 12.87%) compared to the PE group (23.57%, 95% CI: 21.22– 30.52%), P< 0.001. The RE group also showed lower incidences of sinus tachycardia, sinus bradycardia, and required less support from vasoactive agents (P< 0.001). Additionally, the RE group experienced smaller fluctuations in blood pressure and heart rate (P< 0.05). Both groups achieved a 100% sedation success rate. Notably, the RE group had a longer induction period but a quicker recovery time (P< 0.001), and lower rates of respiratory depression (P=0.006) and injection pain (P< 0.001).Conclusion: Remimazolam combined with esketamine offers superior hemodynamic stability and significantly reduces adverse event rates compared to propofol plus esketamine in elderly patients undergoing painless colonoscopies, while maintaining effective sedation.Keywords: remimazolam, esketamine, colonoscopy, elderly patients, hemodynamic effects

Imène Gouia,1 Florence Joulain,1 Yi Zhang,2 Christopher Ll Morgan,3 Asif H Khan4 1Health Economics and Value Assessment, Sanofi, Gentilly, France; 2Medical Affairs, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA; 3Epidemiology, Pharmatelligence Ltd, Cardiff, UK; 4Global Medical, Sanofi, Bridgewater, NJ, USACorrespondence: Imène Gouia, Sanofi, 82 Avenue Raspail, Gentilly, Cedex, 94255, France, Tel +33786980603, Email Imene.Gouia@sanofi.comPurpose: Global prevalence of pediatric asthma and associated morbidity and mortality has continuously increased. Asthma is the most common chronic illness in children in the UK; however, recent epidemiology data are lacking. This analysis describes the overall prevalence and burden of illness of asthma in children.Methods: This was a retrospective, longitudinal, database analysis using the Clinical Practice Research Datalink database. Primary care records of 19,330 patients (6– 11 years) between January 1 and December 31, 2017, were analyzed. Asthma prevalence was assessed by severity (as described by Global Initiative for Asthma 2017 guidelines), and symptoms, comorbidities, and treatments were compared between asthma patients and matched non-asthmatic controls. Results are presented descriptively; logistic regression analyses were performed for asthma symptoms.Results: The estimated prevalence of pediatric asthma was 6.5% (95% CI: 6.4– 6.5) in the UK (mild: 74.2%; moderate: 15.0%; severe: 10.8%). All patients with moderate or severe asthma and 72.5% of patients with mild asthma were prescribed drug therapy. Most patients with moderate or severe asthma were prescribed a short-acting β 2-agonist (94.9% and 96.0%, respectively), compared with 69.2% of mild asthma patients. Daytime symptoms were reported by 78.1% in those with severe asthma; 34.9% reported night-time symptoms and 30.8% reported an impact on usual activities. Asthma patients had a higher baseline prevalence of comorbidities compared with non-asthmatic controls, notably atopic dermatitis (47.8% in severe asthma versus 20.8% in controls) and allergic rhinitis (13.3% in severe asthma versus 2.0% in controls).Conclusion: This analysis confirmed that asthma remains a common morbidity among children in the UK. Increasing asthma severity was associated with worsening symptoms, and asthma patients had significantly more comorbidities compared with non-asthmatic controls.Keywords: asthma, pediatric, epidemiology, United Kingdom

Qingpeng Xie,1,2,&ast; Jiawen Gu,1,2,&ast; Yujia Sun,3 Jinjia Hong,1,2 Jia Wang,1,2 Na Li,1,2 Yuan Zhang,1,2 Meixian Liu,1,2 Xiaoxuan Zhang,1,2 Xiangyu Zhao,1,2 Xiaohang Chen,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China; 3Nursing College of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohang Chen; Xing Wang, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China, Tel +8618834896163 ; +8613934224604, Email kqyx__cxh@163.com; wangxing@sxmu.edu.cnPurpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state. Keywords: ginger exosome-like nanoparticles, periodontitis, tissue repair, oxidative stress, periodontal ligament fibroblasts

Qingcheng Song,1,2,&ast; Yiran Zhang,3,&ast; Hongzhi Hu,4,&ast; Xuemei Yang,5 Xin Xing,1,2 Jianhua Wu,6 Yanbin Zhu,1,2 Yingze Zhang1,2 1Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Orthopaedic Institution of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 6The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingze Zhang; Yanbin Zhu, Email yzling_liu@163.com; 38600312@hebmu.edu.cnIntroduction: Ferroptosis-driven tumor ablation strategies based on nanotechnology could be achieved by elevating intracellular iron levels or inhibiting glutathione peroxidase 4 (GPX4) activity. However, the intracellular antioxidative defense mechanisms endow tumor cells with ferroptosis resistance capacity. The purpose of this study was to develop a synergistic therapeutic platform to enhance the efficacy of ferroptosis-based tumor therapy.Methods: In this study, a multifunctional nano-catalytic therapeutic platform (mFeB@PDA-FA) based on chemodynamic therapy (CDT) and photothermal therapy (PTT) was developed to effectively trigger ferroptosis in tumor. In our work, iron-based mesoporous Fe3O4 nanoparticles (mFe3O4 NPs) were employed for the encapsulation of L-buthionine sulfoximine (BSO), followed by the modification of folic acid-functionalized polydopamine (PDA) coating on the periphery. Then, the antitumor effect of mFeB@PDA-FA NPs was evaluated using Human OS cells (MNNG/HOS) and a subcutaneous xenograft model of osteosarcoma.Results: mFe3O4 harboring multivalent elements (Fe2+/3+) could catalyze hydrogen peroxide (H2O2) into highly cytotoxic &dot;OH, while the tumor microenvironment (TME)-responsive released BSO molecules inhibit the biosynthesis of GSH, thus achieving the deactivation of GPX4 and the enhancement of ferroptosis. Moreover, thanks to the remarkable photothermal conversion performance of mFe3O4 and PDA shell, PTT further synergistically enhanced the efficacy of CDT and facilitated ferroptosis. Both in vivo and in vitro experiments confirmed that this synergistic therapy could achieve excellent tumor inhibition effects.Conclusion: The nanotherapeutic platform mFeB@PDA-FA could effectively disrupted the redox homeostasis in tumor cells for boosting ferroptosis through the combination of CDT, PTT and GSH elimination, which provided a new perspective for the treatment of ferroptosis sensitive tumors. Keywords: ferroptosis, chemodynamic therapy, photothermal therapy, Fenton reaction, BSO

Chao Wang,1,&ast; Mei Zhao,2,&ast; Yuanyuan Yue,3 Chao Hu,2 Chunqiu Zhou,2 Zhongyi Zhang,2 Yunliang He,4 Yaqi Luo,4 Tao Shen,2 Sijie Dang,4 Yang Yang,4 Yong Zhang2,4 1Traditional Chinese Medicine Department, Qitai Hospital of the Sixth Division, Xinjiang, 831899, People’s Republic of China; 2College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Department of Ultrasound, Chengdu First People’s Hospital, Chengdu, 610095, People’s Republic of China; 4Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Zhang; Yang Yang, Institute of Traditional Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, People’s Republic of China, Email 18692213920@163.com; 18721326@qq.comBackground: Modified Suanmei-Tang (MST) comprises four plants common to both traditional Chinese medicine and culinary applications, and it can potentially alleviate metabolic-associated fatty liver disease (MAFLD) triggered by a high-fat diet (HFD).Purpose: This research aims to investigate the impact and underlying mechanisms of MST in ameliorating MAFLD caused by an HFD.Methods: UHPLC-Q-Orbitrap-MS/MS was used to determine the constituents of MST and to evaluate its effects on MAFLD mouse models. Transcriptomics, network pharmacology, and bioinformatics analysis (including Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis) were utilized to further clarify the mechanisms by which MST acts on MAFLD. The experimental methods included ELISA, real time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, molecular docking, and metabolomics. Transcriptomics was integrated with metabolomics to find correlations between differentially expressed genes and metabolites, and crucial genes were validated through RT-qPCR.Results: A total of 23 components of MST were identified. The formulation was found to alleviate metabolic disorders, obesity, insulin resistance, inflammation, and oxidative stress in mice with MAFLD. The findings indicate that MST promoted autophagy by suppressing phosphorylation in the PI3K/AKT/mTOR pathway and enhancing lipid management in the livers of MAFLD mice.Conclusion: MST could effectively improve lipid metabolism disorders and liver lipid deposition in MAFLD mice, and its mechanism might be related to regulating the PI3K/AKT/mTOR pathway to improve autophagy. Keywords: modified Suanmei-Tang, MAFLD, transcriptomics, network pharmacology, metabolomics

Yue Fang,1,2,&ast; Yi Yue,3,&ast; Sensen Hao,1 Ying Zhang,4 Nan Liu,1 Shengling Wang,1 Yan Li,1 Hongzhi Wang1 1Galactophore Oncology Center, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei City, Anhui Province, People’s Republic of China; 2Science Island Branch, Graduate School of University of Science and Technology of China, Hefei City, Anhui Province, People’s Republic of China; 3The Second Clinical College, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhi Wang, Email wanghz@hfcas.ac.cnBackground: Serpin B9 is highly expressed in breast cancer, melanoma, and various malignant cells and inhibits NK cell killing through the Serpin B9-GrB axle. However, the current studies have only validated the role of Serpin B9 in vivo and vitro, and lack of systematic studies on the expression of Serpin B9 in patients’ tumor tissues and its prognostic implications. In this study, we propose to further validate the role of Serpin B9 by comparing its expression level in tissues of lung adenocarcinoma patients and its correlation with the efficacy of immunotherapy.Methods: This study included 200 patients with LUAD between Feb 2022 and Feb 2023. IHC scoring assessed Serpin B9 expression in the tumor and adjacent tissues, with an H-score of 2 as the cutoff value. Patients were divided into high- and low-expression groups. T-tests were used to compare Serpin B9 expression and treatment efficacy between the tumor and adjacent tissues in both groups. Baseline characteristics were compared using X2 tests. Prognostic risk factors were identified using Cox regression and Kaplan-Meier survival curves.Results: The expression level of Serpin B9 in LUAD tumor tissues are higher than adjacent tissues and positively correlated with the TNM stage and negative correlated with PFS in patients with LUAD. Additionally, immunotherapy efficacy was inversely correlated with Serpin B9 expression.Conclusion: The increased expression of Serpin B9 in LUAD tumor tissues is negatively linked to prognosis and immunotherapy efficacy. This underscores their potential as prognostic and therapeutic targets.Keywords: serine proteinase inhibitor B9, lung adenocarcinoma, progression free survival, PD-1/PD-L1

Liudan Huang,1 Xuexin Chen,2 Yuhua Zhang1 1Department of Pediatrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Neonatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liudan Huang, Department of pediatrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China, Email 15917932267@163.comBackground: Neonatal respiratory distress syndrome (NRDS) is common in preterm infants. Prognostic nutritional index (PNI)((albumin (g/L)+(5×total lymphocyte count (109/L)) is a comprehensive indicator of nutritional and immune levels, and associated with several diseases. The relationship between PNI and the risk of NRDS in newborns of different gestational ages remains unclear.Methods: A total of 2722 preterm infants were included in this retrospective study. PNI level and clinical records of these neonates (adverse pregnancy and birth history, amniotic fluid contamination, nuchal cord, placental abnormality, mode of delivery, gender and birth weight of neonates, Apgar scores) were collected. The clinical features of the infants with and without NRDS were compared. Logistic regression analysis was used to evaluate the relationship between PNI and NRDS in newborns with different gestational ages.Results: There were 1226 neonates with NRDS and 1496 without NRDS. The differences in the proportions of placenta abnormality, cesarean section, and small for gestational age (SGA) among infants with 34– 37 weeks, 28+1-33+6 weeks, and ≤ 28 weeks gestational age were statistically significant. Logistic analysis showed that cesarean section (odds ratio (OR): 1.550, 95% confidence interval (CI): 1.197– 2.007, p=0.001), and low PNI (OR: 1.417, 95% CI: 1.110– 1.808, p=0.005) were associated with NRDS in infants born at 34– 37 weeks gestational. Adverse pregnancy and birth history (OR: 1.507, 95% CI: 1.124– 2.019, p=0.006), SGA (OR: 1.994, 95% CI: 1.455– 2.733, p< 0.001), and low PNI (OR: 1.626, 95% CI: 1.230– 2.149, p=0.001) were associated with NRDS in infants with 28+1-33+6 weeks gestational age. Low PNI (OR: 5.512, 95% CI: 1.555– 19.536, p=0.008) was associated with NRDS in infants with ≤ 28 weeks gestational age.Conclusion: The risk factors for NRDS in preterm infants with different gestational ages were different. But the low PNI level is associated with an increased risk of NRDS in preterm infants with all different gestational ages.Keywords: neonatal respiratory distress syndrome, preterm infants, risk factors, prognostic nutritional index

Zhenkang Liang,&ast; Zehong Chen,&ast; Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosis

Yawen Zhang,&ast; Qiao Li,&ast; Lirong Li, Hao Guo, Fang He Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang He, Email hetrue@163.comPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a significant public health threat, particularly as a superbug responsible for nosocomial infections. In this study, we report a novel sequence type 6758 of K. pneumoniae harboring the blaNDM-1 gene.Material and Methods: Antimicrobial susceptibility testing was conducted according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). The complete genome sequence of the strain was determined using the Illumina NovaSeq 6000 platform and long-read MinION sequencer. Genomic features and resistance mechanisms of the strain were further comprehensively analysed using various bioinformatics approaches.Results: Antimicrobial susceptibility testing revealed that this strain exhibited resistance to multiple antimicrobials, including ceftazidime, ceftriaxone, cefazolin, cefepime, imipenem, meropenem, ampicillin/sulbactam, and sulfamethoxazole/trimethoprim. The genome analysis identified sixteen resistance genes. The blaNDM-1 carbapenemase gene is located on a 47,823 bp IncX3-type plasmid (pNDM-CRKP331). A total of 41 K. pneumoniae strains carrying similar IncX3-type plasmids were retrieved from the NCBI database, representing 20 sequence types (STs) across 11 countries. The most common resistance gene carried by these IncX3-type plasmids is blaNDM, and all these plasmids contain only the blaNDM gene. The blaNDM-carrying IncX3-type plasmids are widely prevalent in K. pneumoniae in China, spanning 15 STs.Conclusion: In summary, our study reports the first genome sequence of an ST 6758 K. pneumoniae strain containing the class B β-lactamase blaNDM-1 isolated from a clinical sample. Given the global emergence of blaNDM, measures should be taken to prevent the spread of these blaNDM-carrying IncX3-type plasmids. Our findings contribute to the understanding of the transmission mechanisms of blaNDM in K. pneumoniae.Keywords: carbapenem-resistant Klebsiella pneumoniae, blaNDM-1, whole-genome sequencing, IncX3 type plasmid, ST6758

Zhoushu Zheng,1 Lulu Yan,2,3 Lu Ding,1 Yinghui Zhang,1 Meihong Wang,1 Yihui Yang,1 Junhua Wu,3 Changshui Chen,3 Ming Tang,1 Haibo Li2,3 1Department of Otolaryngology Head and Neck Surgery, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 2The Central Laboratory of Birth Defects Prevention and Control, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 3Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, The Affiliated Women and Children’s Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Haibo Li, The Central Laboratory of Birth Defects Prevention and Control, Women and Children’s Hospital of Ningbo University, No. 339, Liuting Road, Haishu District, Ningbo City, Zhejiang Province, People’s Republic of China, Email lihaibo-775@163.com Ming Tang, Department of Otolaryngology head and neck surgery, Ningbo Women and Children’s Hospital, No. 339, Liuting Road, Haishu District, Ningbo City, Zhejiang Province, People’s Republic of China, Email tmtm-50@163.comIntroduction: Syndromic hearing loss (SHL) is characterized by distinctive clinical phenotypes as well as genetic and phenotypic heterogeneity. More than 400 species of SHL have been described, the majority of which are autosomal dominant.Methods: 11 forms of SHL were obtained from 14 unrelated families with probands ranging in age from 5 to 78 months. The results of whole exome sequencing(WES), audiological characteristics, middle and inner ear radiological findings, and additional clinical phenotype characteristics were retrospectively analyzed.Results: Fourteen people with SHL were found. Two of them had Waardenburg syndrome, two had Branchio-Oto-Renal syndrome, two had CHARGE syndrome, and one had Treacher Collins syndrome, Kleefstra syndrome, Muenke syndrome, Osteopathia Striata with Cranial Sclerosis, Ayme-Gripp syndrome, Tatton-Brown-Rahman syndrome, Stickler syndrome, or Stapes Ankylosis with Broad Thumbs and Toes. In this investigation, ten variants were first reported.Discussion: The combination of a neonatal hearing screening and WES can diagnose syndrome-type hearing loss in infancy and childhood, according to our findings, expansion of the gene variant spectrum and phenotype for various age groups of SHL is essential and can provide valuable guidelines for clinical intervention decisions. It is imperative for medical practitioners to conduct diligent and prolonged patient monitoring due to the inherent variability in both the auditory impairment and the comprehensive clinical manifestation of SHL.Keywords: syndromic hearing loss, whole exome sequencing, neonatal hearing screening, phenotype-genotype correlations

Jing Hu, Yang Song, Yuxing Zhang, Peng Yang, Siyu Chen, Zhaoyan Wu, Jun Zhang Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cnPurpose: This study examines the effects and mechanisms of catalpol (CAT) on the proliferation and osteogenic differentiation of cultured human periodontal ligament stem cells (hPDLSCs) in vitro and assesses the impact of CAT on periodontal remodeling in vivo using an orthodontic tooth movement (OTM) model in rats.Methods: hPDLSCs were cultured in a laboratory setting, and their proliferation and osteogenic differentiation were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. Additionally, the expression of collagen type 1 (COL-1), ALP, and runt-related transcription factor-2 (RUNX-2) was evaluated through qRT-PCR and Western blot analysis. To verify the function of the estrogen receptor-α (ER-α)-mediated phosphatidylinositol-3-kinase-protein kinase B (PI3K/AKT) pathway in this mechanism, LY294002 (a PI3K signaling pathway inhibitor) and the ER-α specific inhibitor methyl-piperidine-pyrazole (MPP) were used. The osteogenic markers ER-α, AKT, and p-AKT (phosphoprotein kinase B) were identified through Western blot analysis. Eighteen male Sprague-Dawley rats were assigned to two groups randomly: a CAT group receiving CAT and a control group receiving an equivalent volume of saline. Micro-computed tomography (micro-CT) analysis was employed to evaluate tooth movement and changes in alveolar bone structure. Morphological changes in the periodontal tissues between the roots were investigated using hematoxylin and eosin (HE) staining and tartaric-resistant acid phosphatase (TRAP) staining. The expression of COL-1, RUNX-2, and nuclear factor-κB (NF-κB) ligand (RANKL) was assessed through immunohistochemical staining (IHC) to evaluate periodontal tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences among more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by the Tukey’s test. Values of p

Xiaoxi Fan,1,2,&ast; Wenli Zhang,2,3,&ast; Ruihan Zheng,1 Yucong Zhang,1 Xianhui Lai,4 Jibo Han,5 Zimin Fang,1 Bingjiang Han,5 Weijian Huang,1 Bozhi Ye,1,2 Shanshan Dai1,6 1The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2The Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Yuhuan County People’s Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 6The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanshan Dai; Bozhi Ye, Email shanshandai137@163.com; fredye2012@163.comAim: Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy.Methods: C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd−/−) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy.Results: GSDMD was activated in the kidneys of mice induced by Ang II (P < 0.001). This activation was primarily observed in the renal tubular epithelial cells (P < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (P < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (P < 0.01). Mechanistically, GSDMD increased Ang II–induced GATA binding protein 2 (GATA2) transcription factor expression (P < 0.01). GATA2 also bound to the aquaporin 4 (Aqp4) promoter sequence and facilitated Aqp4 transcription (P < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II–induced renal injury and fibrosis (P < 0.01).Conclusion: GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy. Keywords: gasdermin D, hypertensive nephropathy, pyroptosis, angiotensin II, aquaporin 4, GATA binding protein 2

Meng Xiang,1,&ast; Chengzhi Chen,2,&ast; Yuting Chen,1,&ast; Yuhan Zhang,1 Lei Shi,1 Yan Chen,1 Jie Li,2 Bowen Li,1 Bin Zeng,2 H Rosie Xing,1 Jianyu Wang,2 Zhen Zou2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Zou; Jianyu Wang, Email zouzhen@cqmu.edu.cn; 102758@cqmu.edu.cnIntroduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer. Keywords: silicon nanoparticles, lung cancer, macrophage polarization, NF-κB, glycolysis

Ying Zhang,1,&ast; Ziyun Shi,2,&ast; Haixia Liang,1 Meixia Chen,1 Yan Sun,1 Fujun Shang,3 Yi Wan4 1Department of Obstetrics and Gynecology, Xijing 986 hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Obstetrics, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Cardiology, Xi’an Gem Flower Changqing Hospital, Xi’an, Shaanxi, People’s Republic of China; 4Department of Health Service, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wan, Department of Health Service, Fourth Military Medical University, No. 169 Changle Xilu, Xi’an, 710032, People’s Republic of China, Tel/Fax +86-29-84712676, Email wanyi@fmmu.edu.cn Fujun Shang, Department of Cardiology, Xi’an Gem Flower Changqing Hospital, Xi’an, Shaanxi, 710201, People’s Republic of China, Tel/Fax +86-29-86022756, Email shangfujun4@163.comObjective: Validation of blood pressure (BP) monitors in pregnant women are needed to ensure the accurate measurement of BP in pregnancy. Therefore the study aimed to evaluate the measurement accuracy of the G.LAB MD41A0 oscillometric automatic upper-arm blood pressure monitor in pregnancy and pre-eclampsia women according to the AAMI/ESH/ISO Universal Standard (ISO 81060– 2:2018).Methods: A total of 45 pregnant women were included in the cross-sectional validation study. The same left-arm sequential method was used for blood pressure measurement, and the blood pressure differences between the test device and the mercury standard reference were assessed according to the AAMI/ESH/ISO Universal Standard.Results: The participants included 15 normotensives, 15 gestational hypertension and 15 pre-eclampsia. The average (mean ± SD) differences between the device and mercury standard was − 0.84± 3.88 mmHg and − 0.58± 3.35 mmHg for systolic and diastolic blood pressure, respectively, for the validation Criterion 1. The SD of the averaged differences between the device and reference readings per participant was 2.92 mmHg and 2.28 mmHg for systolic and diastolic blood pressure, respectively, for the Criterion 2 of the universal standard.Conclusion: The G.LAB MD41A0 automatic upper-arm blood pressure monitor fulfills the criteria of the AAMI/ESH/ISO Universal Standard and can be recommended for clinical use and self-measurement in pregnancy and pre-eclampsia.Keywords: blood pressure monitor, validation, universal standard, pregnancy, pre-eclampsia

Haikun Yang,1,2,&ast; Yan Zhang,3,&ast; Wen He1,4 1Meizhou Clinical Institute, Shantou University Medical College, Meizhou, Guangdong Province, People’s Republic of China; 2Department of Gynaecology, Meizhou People’s Hospital, Meizhou, Guangdong Province, People’s Republic of China; 3Department of Radiology, the First People’s Hospital of GuiYang, Guiyang, Guizhou Province, People’s Republic of China; 4Meizhou Academy of Medical Sciences, Meizhou People’s Hospital, Meizhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen He, Email doctorhoman@163.comAbstract: Pelvic congestion syndrome (PCS) is a chronic condition primarily characterized by pelvic pain and heaviness, with vaginal bleeding being a rare but significant symptom. We present two cases of PCS-related vaginal bleeding, emphasizing the necessity of considering PCS in differential diagnoses for abnormal vaginal bleeding. A 28-year-old Chinese woman presented with abnormal vaginal bleeding exacerbated by abdominal pressure during activities like squatting or defecation. Imaging revealed a dilated right ovarian vein, and transcatheter venography confirmed Nutcracker syndrome. After undergoing transcatheter foam sclerotherapy, her symptoms resolved. The second case involves a 29-year-old Chinese woman with similar symptoms; imaging and venography identified a dilated left ovarian vein. Following sclerotherapy, her symptoms also alleviated. These cases underscore the importance of recognizing PCS as a potential cause of abnormal vaginal bleeding and demonstrate the efficacy of transcatheter foam sclerotherapy in managing this condition. Integrating clinical presentation with imaging findings is crucial for timely diagnosis and effective treatment, ultimately improving patient outcomes.Keywords: pelvic congestion syndrome, vaginal bleeding, transcatheter foam sclerotherapy, nutcracker syndrome

Jaina Razbek,1 Yanggui Chen,2 Jiandong Yang,2 Yaying Zhang,1 Baofeng Wen,1 Junan Wang,1 Xiaomin Wang,1 Guliziba Kuerbanjiang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2Department of Prevention and Control of Tuberculosis, Urumqi Centre for Disease Control and Prevention, Urumqi, 830011, People’s Republic of ChinaCorrespondence: Mingqin Cao, Email cmq66@126.comPurpose: Latent tuberculosis infection (LTBI) is a critical stage in tuberculosis (TB)control, and few studies have addressed the role of vitamin D receptor(VDR) gene polymorphisms in differentiating between TB and late-onset TB from an immunogenetic perspective.Patients and Methods: Recruitment of tuberculosis patients and latently infected population in Urumqi, Xinjiang, and use of propensity score matching(PSM) to match the two groups and control confounding to further construct a Bayesian network to analyze causal associations between VDR polymorphisms and tuberculosis disease status.Results: 137 LTBI and 237 TB were obtained through PSM. Logistic regression showed that the VDR gene BsmI locus, TaqI locus, and ApaI locus were associated with a higher risk of TB in a codominant model (P< 0.05). Further Bayesian network construction showed that occupation and being a VDR gene BsmI locus were direct influences on TB disease status, and the VDR gene TaqI locus played an indirect role through the BsmI locus, and the probability of TB risk was highest in individuals with manual labour and BsmI locus of the C/T type, which was 84.15%.Conclusion: Bayesian network modelling intuitively revealed that individuals with a C/T type of BsmI locus and physical labour are at high risk of TB compared with TB infection, and they are key factors between with TB disease, providing reference evidence for controlling TB progression.Keywords: tuberculosis, disease state, vitamin D receptor, propensity score matching, Bayesian network

Xiaozhu Zha,1,&ast; Yumei Hao,2,&ast; Yifan Ke,1 Yichun Wang,3 Yujia Zhang2 1Department of Traditional Chinese Medicine, Anqing Medical College, Anqing, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Radiation Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yichun Wang; Yujia Zhang, Email wangechun321@sina.com; zhyj@imm.ac.cnBackground: Liver fibrosis is a necessary pathological process in many chronic liver diseases. Studies have shown that the progression of chronic liver disease can be slowed by rational intervention in hepatic fibrosis. Berberine (BBR), a natural extract of Phellodendron amurense, inhibits the development of liver fibrosis through several mechanisms. However, the clinical application of BBR is limited due to its low solubility. Drug delivery systems have been developed to improve the solubility of hydrophobic drugs and increase their efficacy in treating the liver fibrosis.Methods: In this study, a biocompatible nanomicelle was constructed by thin-film dispersion method using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) as a carrier to encapsulate BBR (PVCL-PVA-PEG/BBR-MCs) to improve the solubility of BBR and reduce the systemic side effects. The ability to inhibit HSC-T6 cell activation of PVCL-PVA-PEG/BBR-MCs was evaluated in vitro. The anti-hepatic fibrosis effects of PVCL-PVA-PEG/BBR-MCs were investigated in vivo.Results: PVCL-PVA-PEG/BBR-MCs have a uniform spherical shape with a mean particle size of 60.04 ± 0.027 nm and a potential of 1.49 ± 0.32 mV. It had an encapsulation efficiency of 98.52% ± 0.70 and drug loading content of 6.16% ± 0.04. Compared to free BBR, PVCL-PVA-PEG/BBR-MCs significantly inhibited HSC-T6 cell activation and TGF-β 1-induced HSC-T6 cell migration in vitro. In vivo biodistribution experiments showed significantly improved hepatic distribution of PVCL-PVA-PEG/DiD-MCs compared to free DiD, suggesting that PVCL-PVA-PEG micelles enhance the ability of BBR to enter the liver and improve therapeutic efficacy. After treatment, PVCL-PVA-PEG/BBR-MCs significantly improved fibrotic liver structure and reduced collagen deposition in comparison to the CCl4-treated group; the treatment outcome was more effective than that of the free BBR group.Conclusion: Our results demonstrate the advantages of encapsulating BBR in PVCL-PVA-PEG micelles and highlight the potential of PVCL-PVA-PEG/BBR-MCs as a therapeutic strategy for the treatment of liver fibrosis. Keywords: liver fibrosis, berberine, hepatic stellate cells, PVCL-PVA-PEG, drug delivery system

Yang Li,1 Yuhan Zhang,1 Na Feng,2 Fan Yu,1 Bin Liu3 1Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 2Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of ChinaCorrespondence: Fan Yu; Bin Liu, Email yufan2017@jlu.edu.cn; liub18@mails.jlu.edu.cnPurpose: Bladder cancer is a common malignancy of the urinary system and the development of noninvasive therapeutic methods is imperative to avoid radical cystectomy, which results in a poor quality of life for patients.Methods: In this study, ultrasmall copper–palladium nanozymes decorated with cysteamine (CPC) nanoparticles (NPs) were synthesized to enhance the efficacy of radiotherapy (RT) in treating bladder cancer. CPC NPs react with intracellular overexpressed H2O2 in the tumor microenvironment to produce large quantities of reactive oxygen species (ROS) and induce tumor cell apoptosis. Furthermore, the CPC nanozymes can generate ample oxygen within tumors by utilizing H2O2, addressing hypoxia conditions, and mitigating radioresistance. Additionally, CPC facilitates the oxidation of glutathione (GSH) into oxidized glutathione disulfide (GSSG), blocking the self-repair mechanisms of tumor cells post-treatment. Simultaneously, CPC enhances the ionization energy deposition effect on tumor cells.Results: The results demonstrate an increased level of ROS and an elevation in oxygen content at the tumor site. Importantly, tumor growth was restrained without apparent systemic toxicity during the combined treatment.Conclusion: In summary, this study highlights the potential of CPC nanozyme-mediated radiotherapy as a promising avenue for the effective treatment of bladder cancer and demonstrates its potential for future clinical applications in the synergistic therapy of bladder cancer.Keywords: bladder cancer, radiotherapy, nanozyme, tumor microenvironment, hypoxia

Xiying Zhang,1 Zhixia Jiang,2 Aiai Huang,3 Fuyan Zhang,4 Yuancheng Zhang,5 Fang Zhang,6 Lin Gao,7 Xiaoling Yang,8 Rujun Hu9 1Department of Intensive Care Unit, Jinsha County People’s Hospital, Bijie, Guizhou Province, 551800, People’s Republic of China; 2Office of the Director, Guizhou Nursing Vocational and Technical College, Guiyang, Guizhou Province, 550081, People’s Republic of China; 3Department of Nursing, Panyu Maternal and Child Care Service Center of Guangzhou, Guangzhou, Guangdong Province, 511400, People’s Republic of China; 4Department of Nursing, Jinsha County People’s Hospital, Bijie, Guizhou Province, 551800, People’s Republic of China; 5Department of Orthopaedics, Jinsha County People’s Hospital, Bijie, Guizhou Province, 551800, People’s Republic of China; 6Surgical Teaching and Research Office, Guizhou Nursing Vocational and Technical College, Guiyang, Guizhou Province, 550081, People’s Republic of China; 7Department of Endocrinology, Jinsha County People’s Hospital, Bijie, Guizhou Province, 551800, People’s Republic of China; 8Comprehensive Department of Nursing, Guizhou Nursing Vocational and Technical College, Guiyang, Guizhou Province, 550081, People’s Republic of China; 9Department of Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 563000, People’s Republic of ChinaCorrespondence: Xiying Zhang, Department of Intensive Care Unit, Jinsha County People’s Hospital, Yangdeng Community, Xiluo Street, Jinsha County, Bijie City, Guizhou Province, People’s Republic of China, Tel +86 15285207705, Email zhang_xiying9@yeah.netObjective: To identify the latent trajectories of activities of daily living (ADL) disability and the influential factors among adults with post-intensive care syndrome (PICS).Methods: We evaluated five-time longitudinal data about PICS diagnosed in 434 of 593 assessed patients (73.19%). Disability was measured by the Barthel index scale, which grades individuals according to how difficult it is to carry out ADL. We utilized the growth mixture model (GMM) to identify latent trajectories and associated factors.Results: Two groups with distinct trajectories of ADL disability were identified, including the Severe Disability Sustained Group and the Disability Recovery Group. People who were of advanced age transferred to another hospital for treatment, or had cognitive impairment or depression were more likely to be classified into the Severe Disability Sustained Group (P < 005).Conclusion: There are two potential trajectories of ADL disability in patients with PICS, which are the severe disability persistence group and the disability recovery group. Improvement in cognitive impairment or depression may contribute to recovery from disability, transfer to hospital or advanced age may not be conducive to recovery of ADL ability, and disability may last longer.Keywords: activities of daily living, critical illness, disability, growth mixture model, post-intensive care syndrome

Zhaobai Lao,1,&ast; Xuliang Fang,1,&ast; Shuchao Shen,1,&ast; Yuliang Zhang,2,&ast; Xin Chen,1 Helou Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Ronghua Bao,2 Taotao Xu,3 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Changfeng Hu,4 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 4College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhudianzhuifeng@163.com Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnPurpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations.Methods: The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.Results: MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.Conclusion: Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.Keywords: systemic lupus erythematosus, intervertebral disc degeneration, nucleus pulposus, pyroptosis, NRF2/KEAP1/NF-κB pathway

Xiang Tang,1,2,&ast; Jinbin Chen,1,2,&ast; Wei Peng,1,2,&ast; Zhoutian Yang,1,2 Li Hu,1,2 Zhiwei Ye,1,2 Yizhen Fu,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang,1,2 Jun-Cheng Wang1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaojun Zhang; Jun-Cheng Wang, Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhangyuj@sysucc.org.cn; wangjch@sysucc.org.cnObjection: To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).Methods: In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Results: Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0– 13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.Conclusion: Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.Keywords: hepatocellular carcinoma, immune checkpoint inhibitor, bevacizumab, hepatic arterial infusion chemotherapy, adverse event

Jiamin Yu,1 Yongxia Chen,1 Xiaoyan Pan,1 Ji Chen,1 Zhenhua Mai,1 Yuanli Zhang,1 Xiaoyan Wang,2– 4 Gaosheng Zhou,5 Sayed Adam Bukhari,6 Daqing Ma,6,7 Liehua Deng1 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, People’s Republic of China; 2Doctoral Scientific Research Center, Lianjiang People’s Hospital, Zhanjiang, 524400, People’s Republic of China; 3Affiliated Lianjiang People’s Hospital, Guangdong Medical University, Zhanjiang, 524400, People’s Republic of China; 4Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023, People’s Republic of China; 5Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 6Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, UK; 7Perioperative and Systems Medicine Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaCorrespondence: Liehua Deng, Email glinson@126.comPurpose: The early diagnosis of septic cardiomyopathy remains a challenge. The present work aims to evaluate the diagnostic and prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in septic cardiomyopathy when compared with traditional myocardial biomarkers.Methods: In the 143 sepsis enrolled patients, 67 and 76 patients were classified as non-septic cardiomyopathy and septic cardiomyopathy, respectively. Their blood samples were harvested up to 14th day after hospital admission for measurements of sTREM-1 and other biomarkers, such as N-terminal pronatriuretic peptide (NT-proBNP), highly sensitive troponin (TNT-HS), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), etc. All the data were collected at 8:00 a.m. The area under the receiver operating characteristic curve was obtained to assess the diagnostic accuracy of those biomarkers. The Log rank test was utilized to evaluate the prognostic value of sTREM-1 on septic cardiomyopathy.Results: Circulating sTREM-1 showed a high specificity (88.1%) and moderate sensitivity (64.5%) to distinguish patients with septic cardiomyopathy in the 143 septic patients. The diagnostic efficiency of sTREM-1 was higher than inflammatory biomarkers and traditional myocardial markers. Logistic regression revealed that plasma sTREM-1 was an independent predictor of septic cardiomyopathy. Furthermore, in the whole septic cardiomyopathy cohorts, the sTREM-1 levels in the non-survivors were significantly higher than those of survivors during ICU stay. In addition, the left ventricular systolic dysfunction had a high odds ratio (3.968) to predict 90-day mortality in septic patients with cardiomyopathy.Conclusion: High plasma sTREM-1 level may be a diagnostic marker in predicting ICU poor outcome of patients with septic cardiomyopathy.Keywords: sepsis, septic cardiomyopathy, diagnosis, sTREM-1

Xiaosu Guo,1– 4,&ast; Huimin Shi,1,2,&ast; Yuteng Sun,1 Yuan Xing,1– 3 Xin Guo,1– 3 Zhiyuan Shen,1– 3 Mengyi Zheng,1 Yaxin Zhang,1 Yicun Jia,1 Ye Li,1 Junqiang Bao,1,2 Shujuan Tian1– 3 1Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei Hospital, Xuanwu Hospital, Capital Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Neuromedical Technology Innovation Center of Hebei Province, Shijiazhuang, Hebei, People’s Republic of China; 4Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shujuan Tian; Junqiang Bao, Department of Neurology, The First hospital of Hebei Medical University, Shijiazhuang, Hebei, 050030, People’s Republic of China, Tel +86-0311-87156309, Email 57203005@hebmu.edu.cn; 57903004@hebmu.edu.cnPurpose: To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features.Patients and Methods: We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals.Results: Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients.Conclusion: Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.Keywords: anti-LGI1 antibody encephalitis, epilepsy, electroencephalogram, brain network functional connectivity, immunotherapy

Jingjing Li,1 Yu Zhang,2 Rui Wu,1 Guodong Ma,1 Li Sheng,1 Yun Feng,1 Yang Han,1 Lina Zhang,1 Janfeng Guo,1 Rongbo Li1 1Department of Infectious Diseases, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region, 010000, People’s Republic of China; 2Department of Dermatology and Venereology, Hohhot, Inner Mongolia Autonomous Region People’s Hospital, 010000, People’s Republic of ChinaCorrespondence: Jingjing Li, Department of Infectious Diseases, Hohhot First Hospital, No. 148, South Second Ring Road, Zhaojun Road, Yuquan District, Hohhot, Inner Mongolia Autonomous Region, 010000, Tel +86-18047422188, Email 1151664990@qq.comPurpose: To explore the value of different inflammatory markers in predicting the severity of coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 116 patients with COVID-19 in patients with T2DM were collected from December 2022 to March 2023 and were divided into a mild case group (77 cases) and a severe case group (39 cases). The ratio of neutrophil to lymphocyte (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil to lymphocyte × platelet ratio (NLPR), lymphocyte ratio to monocyte (LMR), systemic inflammatory response index (SIRI), systemic inflammatory index (SII), systemic inflammatory composite index (AISI), procalcitonin (PCT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were compared between the two groups. The screening effect of each variable on the progression of the disease was analyzed using receiver operating characteristic (ROC) curves.Results: NLR, PLR, NLPR, MLR, SIRI, SII, AISI, LDH, CRP and PCT in severe case group were higher than those in mild case group (P< 0.05), and LMR was lower than those in mild case group (P< 0.05). ROC curve analysis further demonstrated the diagnostic performance of these biomarkers, with PCT having the largest area under the ROC curve (AUCROC) of 0.83.Conclusion: NLR, PLR, NLPR, SIRI, SII, LDH, CRP and PCT demonstrate greater reliability in diagnostic value and clinical utility for predicting the severity of COVID-19 in patients with T2DM.Keywords: COVID-19, T2DM, inflammatory index, LDH, CRP, PCT

Jinlei Zhou,1,&ast; Shanggao Xie,1,&ast; Sen Xu,1,&ast; Yuan Zhang,2 Yanlei Li,1 Qice Sun,2 Jun Zhang,1,3 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie Hospital, Bijie, 551700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158&num;, Hangzhou, Zhejiang, People’s Republic of China, Email spinezhaotingxiao@163.com Jun Zhang, Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie hospital, Guanghui Road 112&num;, Bijie, Guizhou, People’s Republic of China, Email spinecarezhangjun@163.comObjective: Comprehensive analyses of the burden of musculoskeletal disorders (MSDs) are crucial for deepening our understanding of their impact on population health and for evaluating progress toward achieving international health goals.Study Design: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021.Methods: We gathered data on the number of prevalent cases, incidences, deaths, and disability-adjusted life years (DALYs) for MSDs from 1990 to 2021. Subsequently, crude indicators, age-standardized rates (ASRs) and estimated annual percentage change (EAPC) were calculated for MSDs from 1990 to 2021 at the global, regional, national, age and gender levels. Finally, decomposition analysis, frontier analysis, and EAPC cluster analysis were employed to examine changes in the indicators and the factors influencing them.Results: In 2021, there were 367,193,430 incident cases and 1,686,561,517 prevalent cases of MSDs globally. Between 1990 and 2021, the age-standardized incidence rates (ASIR) declined marginally from 4641.5 to 4351.79 cases per 100,000 population [EAPC: − 0.16 (− 0.19 to − 0.13)], while the age-standardized DALY rates (ASDR) increased from 1886.2 to 1908.87 per 100,000 population [EAPC: 0.09 (0.07 to 0.11)]. The ASRs were markedly elevated in the high SDI regions in comparison to the remaining SDI regions. The EAPC and its phase clustering analyses indicated a notable upward trajectory in the burden of MSDs in the low and middle SDI regions, particularly in Central Asia. The prevalence of MSDs is highest among individuals aged 50– 59 years and among women. At the global level, the burden of MSDs is 1.43 to 2.30 times higher for women than for men.Conclusion: From 1990 to 2021, the burden of MSDs has been concentrated in high SDI regions, with a gradual shift towards low and middle SDI regions.Keywords: musculoskeletal disease, global burden of disease, prevalence, incidence, DALYs, epidemiology

Yule Wang,&ast; Bei Li,&ast; Yingjuan Zhang,&ast; Ruiling Lu, Qianzhuo Wang, Yue Gao Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Gao, Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, 261 huansha Road, Shangcheng District, Hangzhou, 310006, People’s Republic of China, Email gaoyue@hospital.westlake.edu.cnBackground: Acute lung injury (ALI) is a life-threatening clinical syndrome with high mortality. Currently, the safe and effective therapies for ALI patients are still limited. Qingfei Huoxue decoction (QFHXD) is a hospital agreement prescription for treating pulmonary diseases and displays a remarkable efficacy. However, the pharmacological effect of QFHXD on preventing lipopolysaccharide (LPS)-induced ALI has yet to be reported, let alone questions of potential molecular mechanisms and anti-ALI active substances.Methods: To answer the above-mentioned questions, histopathological observation and kit detection were performed to estimate the protective effect of QFHXD pretreatment against LPS-induced ALI. Based on comprehensive chemical profiling of QFHXD, a network pharmacology strategy and experimental validation were integrated to elucidate the underlying functional mechanisms. The potential anti-ALI active components were identified by molecular docking. The anti-ALI activity of narirutin and its anti-inflammatory mechanism were further validated using animal and molecular experiments.Results: Pretreatment with different doses of QFHXD effectively mitigated histopathological lesions and systemic inflammation caused by LPS stimulation. A detailed analysis of established compound-target-disease network revealed the strong correlation between anti-ALI action of QFHXD and inflammatory mechanisms. Compared with the model group, QFHXD intervention markedly restrained the abnormally increased transcription and protein levels of pro-inflammatory factors (TLR4, NF-κB, IL-6, IL-1β, and TNF-α) in lung tissues of ALI mice. The results of molecular docking highlighted the anti-ALI potential of narirutin targeting to TLR4 and NF-κB p65. In addition to the protective effect of narirutin on suppressing LPS-induced pathological changes, we found that narirutin pretreatment effectively normalized the disordered protein levels of above pro-inflammatory factors of ALI mice.Conclusion: These interesting findings indicate the beneficial effects of QFHXD and its active component narirutin against ALI partly via regulating TLR4/NF-κB mediated inflammation. This work contributes to the development of novel medications for ALI patients. Keywords: Qingfei Huoxue decoction, narirutin, LPS-induced acute lung injury, network pharmacology, TLR4/NF-κB pathway, inflammatory response

Huikang Wang,1– 3,&ast; Xinjun Xu,1– 3,&ast; Haoran Lu,1– 3 Yang Zheng,1– 3 Liting Shao,1– 3 Zhaoyang Lu,2– 4 Yu Zhang,2,3 Xicheng Song2,3 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, QingdaoUniversity, Yantai, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 3Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 4Second Clinical Medicine College, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xicheng Song; Yu Zhang, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.com; superzhang013@163.comPurpose: The pathogenesis of CRSwNP is complex and not yet fully explored, so we aimed to identify the pivotal hub genes and associated pathways of CRSwNP, to facilitate the detection of novel diagnostic or therapeutic targets.Methods: Utilizing two CRSwNP sequencing datasets from GEO, differential expression gene analysis, WGCNA, and three machine learning methods (LASSO, RF and SVM-RFE) were applied to screen for hub genes. A diagnostic model was then formulated utilizing hub genes, and the AUC was generated to evaluate the performance of the prognostic model and candidate genes. Hub genes were validated through the validation set and qPCR performed on normal mice and CRSwNP mouse model. Lastly, the ssGSEA algorithm was employed to assess the differences in immune infiltration levels.Results: A total of 239 DEGs were identified, with 170 upregulated and 69 downregulated in CRSwNP. Enrichment analysis revealed that these DEGs were primarily enriched in pathways related to nucleocytoplasmic transport and HIF-1 signaling pathway. Data yielded by WGCNA analysis contained 183 DEGs. The application of three machine learning algorithms identified 11 hub genes. Following concurrent validation analysis with the validation set and qPCR performed after establishing the mouse model confirmed the overexpression of BTBD10, ERAP1, GIPC1, and PEX6 in CRSwNP. The examination of immune cell infiltration suggested that the infiltration rate of type 2 T helper cell and memory B cell experienced a decline in the CRSwNP group. Conversely, the infiltration rates of Immature dendritic cell and Effector memory CD8 T cell were positive correlation.Conclusion: This study successfully identified and validated BTBD10, ERAP1, GIPC1, and PEX6 as potential novel diagnostic or therapeutic targets for CRSwNP, which offers a fresh perspective and a theoretical foundation for the diagnostic prediction and therapeutic approach to CRSwNP.Keywords: chronic rhinosinusitis with nasal polyposis, key genes, machine learning, immune cell infiltration

Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Zhihong Liu,1,2,&ast; Xiaofang Liang,1,&ast; Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Weiqian Zhang,1,&ast; Shuiying Chen,1,&ast; Zhongyu Bai,1 Menglai Gan,2 Mingwei Chen,2 Ying Zhang,1 Sai Liu,2 Dongjuan Liu1 1Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China; 2Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongjuan Liu, Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email dongjuanliu@cmu.edu.cn Sai Liu, Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email liusai@cmu.edu.cnAbstract: Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients’ quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success. Keywords: oral squamous cell carcinoma, photodynamic therapy, photosensitizers, nanotechnology, biomarkers

Zhen Cheng,&ast; Chunyu Hu,&ast; Yalan Zhang, Jie Zhou, Jiayang Shi, Li Sun, Zongtao Chen Health Management Centre, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongtao Chen; Li Sun, Health Management Centre, First Affiliated Hospital of Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 2368765191 ; +86 2368765228, Email zongtaochen@126.com; 51088031@qq.comPurpose: The aim of this study was to comprehensively compare the predictive effect of 10 body fat indexes on MAFLD in different sex, age and BMI subgroups.Patients and Methods: A total of 5403 physical examination data were included and divided into the MAFLD group (N=2632) and non-MAFLD group (N=2771). The differences and correlation of 10 promising indicators between the two groups were compared, including fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral fat index (VAI), cardiometabolic index (CMI), body adiposity index (BAI), and triglyceride-glucose index (TyG), waist circumference index (WC), body mass index (BMI), waist to height ratio (WHtR). Logistic regression was used to analyze the risk of MAFLD under different adjustment conditions. The operating characteristic curve of different genders, BMI levels and age subgroups was plotted.Results: Male gender, smoking, alcohol drinking, and higher age are risk factors for MAFLD. In addition to BAI, the other 9 indicators had a high correlation with MAFLD, the area under the curve (AUC) value was > 0.7, and the prediction effect was better in females, BMI< 24 kg/m2, age < 35 years subgroup, among which FLI (AUC: 0.912, 95% CI: 0.905– 0.920), LAP (AUC: 0.894, 95% CI: 0.8866– 0.903), and HSI (AUC: 0.881, 95% CI: 0.872– 0.890) have better prediction effects.Conclusion: Our study confirmed the accuracy of body fat-related indexes in predicting MAFLD in people of different sexes, ages, and BMI levels. Among them, FLI, LAP and HSI have high predictive value and can be utilized as simple and cost-effective tools for screening MAFLD in clinical settings.Keywords: metabolic dysfunction-associated fatty liver disease, body fat index, metabolic index, cross-sectional study

Yuan Zhang,1 Lin Fu,2 Xingyu Guo,1 Mengkun Li1 1School of Management, Capital Normal University, Beijing, People’s Republic of China; 2School of Management, China Women’s University, Beijing, People’s Republic of ChinaCorrespondence: Yuan Zhang; Mengkun Li, Email zhangyuan@cnu.edu.cn; limengkun@cnu.edu.cnBackground and Purpose: In public health emergencies, rapid perception and analysis of public demands are essential prerequisites for effective crisis communication. Public demands serve as the most instinctive response to the current state of a public health crisis. Therefore, the government must promptly grasp and leverage public demands information to enhance the effectiveness and efficiency of health emergency management, that is planned to better deal with the outbreak and meet the medical demands of the public.Methods: This study employs dynamic topic mining and knowledge graph construction to analyze public demands, presenting a spatial-temporal evolution analysis method for emergencies based on EBU models. EBU models are three large language models, including ERNIE, BERTopic, and UIE.Results: The data analysis of Shanghai’s city closure and control during the COVID-19 epidemic has verified that this method can simplify the labeling and training process, and can use massive social media data to quickly, comprehensively, and accurately analyze public demands from both time and space dimensions. From the visual analysis, geographic information on public demands can be quickly obtained and areas with serious problems can be located. The classification of geographical information can help guide the formulation and implementation of government policies at different levels, and provide a basis for health emergency material dispatch.Conclusion: This study extends the scope and depth of research on health emergency management, enriching subject categories and research methods in the context of public health emergencies. The use of social media data underscores its potential as a valuable tool for analyzing public demands. The method can provide rapid decision supports for decision-making for public services such as government departments, centers for disease control, medical emergency centers and transport authorities.Keywords: public demands, spatial-temporal evolution, dynamic topic mining, health emergency management, public health emergencies

Jingwen Zhang,1,2,&ast; Guoqiang Zhang,1,2,&ast; JiaJia Wang,1,2,&ast; Yun Xiao,1,2 Xinxin Lu,1,2 Xunhong Lan,1,2 Yan Zhang,1,2 Zhang Dai1,2 1Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang; Zhang Dai, Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Tel +86-0592-2293046, Email zy1983@xmu.edu.cn; 180219034@qq.comBackground: Nosocomial candidemia is a life-threatening condition, and the incidence has increased in recent years. Thorough epidemiological data is still lacking in China.Methods: A retrospective cohort study was conducted to investigate the patients admitted to Zhongshan Hospital Xiamen University from 1 January 2004 to 31 December 2022. This study included 205 individuals who were diagnosed with candidemia as subjects. Additionally, 303 cases with blood cultures were negative during the same period and were from the same department as a control group. We randomly assigned them to the training and validation groups in a 7:3 ratio. The least absolute shrinkage and selection operator regression, univariate and multivariate logistic regression analyses were used to filtrate independent factors associated with nosocomial candidemia. A nomogram model was established based on the selected variables. Receiver operating characteristic (ROC) curve, calibration plots and decision curve analysis (DCA) were used to evaluate clinical utility.Results: Two hundred and five nosocomial candidemia patients were reported, containing a high proportion of Candida albicans (n = 91,44.39%), followed by Candida parapsilosis (n = 40, 19.51%), Candida tropicalis (n = 37,18.05%), Candida glabrata (n = 23, 11.22%) and Candida guilliermondii (n = 9,4.39%). Multiple organ dysfunction syndrome (OR = 10.372, 95% CI: 4.745– 24.14 P < 0.001), increased urea nitrogen of serum (OR=1.088,95% CI: 1.039– 1.144 P< 0.001), decreased albumin of serum (OR = 0.922 95% CI: 0.850– 0.997 P=0.045), mechanical ventilation (OR=4.074,95% CI: 1.397– 12.77 P=0.012), central venous indwelling catheter (OR=7.422,95% CI: 3.189– 18.41 P< 0.001) and solid tumor (OR = 3.036 95% CI: 1.276– 7.359 P=0.012) were identified as independent risk factors of candidemia. The area under the curve (AUC) of the nomogram model was 0.925 (95% CI: 0.898– 0.952) in the training group and 0.946 (95% CI: 0.881– 0.963) in the validation group. The calibration curve revealed good agreement between the probability and the observed values. DCA indicated that this nomogram might be clinically beneficial.Conclusion: The nomogram including multiple organ dysfunction syndrome, elevated blood urea nitrogen, decreased albumin, mechanical ventilation, central venous indwelling catheter and solid tumor could provide reference value to clinicians for identifying nosocomial candidemia.Keywords: candidemia, risk factors, nomogram model, ROC curve

Renjiao Liu,1 Zhouhuiling Li,2 Yanju Zhang,2 Meiyang Du,2 Xincheng Wang,3 Shi Zhang,3 Chunjun Li1,3 1Graduate School, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Chunjun Li, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No. 190 of Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +86-22-13752090635, Email li_chunjun@126.comBackground: Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D.Aim: The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D.Methods: The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR.Results: Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P< 0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P< 0.001).Conclusion: The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established.Keywords: insulin resistance, serum uric acid, HDL-c, triglycerides

Yali Liang,1,&ast; Yunxin Zhang,1,&ast; Yong Feng,2 Yuying Huang,2 Cuiling Zhang1 1Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuiling Zhang, Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13753482546, Email sxbqezcl@163.comPurpose: To assess abusive supervision and organizational silence among nurses and investigate the mediating influence of psychological capital and fear.Background: Since the end of 2019, China’s National Development and Reform Commission (NDRC) department has decided to start the construction of regional medical centers in Shanxi, reducing cross-provincial and cross-regional medical care. In order to improve the overall standard of care in a hospital in a short period of time, health care leadership decision makers may adopt various effective leadership management practices to achieve the set goals and have high work pressure at the same time. In this case, abusive management may occur.Methods: A cross-sectional survey design was employed. In January -March 2024, a convenience sampling method was used to collect data from 470 nurses in a total of 5 hospitals in Shanxi province they were required to complete the questionnaires online anonymously. The chain mediation model was tested using the PROCESS macro program in the SPSS software and multiple linear regression model was used to verify the mediating effect.Results: Psychological capital and fear mediate the relationship between abusive supervision and nurses’ organizational silence, playing indirect mediating roles. Abusive supervision was positively associated with nurses’ organizational silence. Additionally, psychological capital plays a negative mediating role, accounting for 48.48% of the indirect effect, and fear plays a positive mediating role, accounting for 45.83% of the indirect effect. They form a chain intermediary, accounting for 5.69% of the indirect effect.Conclusion: Psychological capital and fear mediate the impact of abusive supervision on nurses’ organizational silence. Positive leadership training should be conducted to help reducing the level of head nurses’ abusive supervision behaviors, while also fostering actions that elevate nurses’ psychological capital levels.Keywords: Abusive supervision, Nurses’ organizational silence, psychological capital, fear, mediating effect

Fengting Wang,1,&ast; Limin Rong,1,&ast; Linlin Luo,2 Fuqin Mu,1 Liju Qian,3 Yandan Qian,4 Xinyao Zhang,1 Yuying Lang,1 Weijia Wang,1 Yan Liu,5,6 Ying Zhang,7 Jianli Wang1,8 1School of Mental Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Hematology, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Shandong Daizhuang Hospital, Jining, Shandong, People’s Republic of China; 4The Third People’s Hospital of Jiashan County, Jiashan, Zhejiang, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 6Center of Evidence-Based Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China; 7School of Public Health, University of Sydney, Sydney, NSW, Australia; 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada&ast;These authors contributed equally to this workCorrespondence: Fengting Wang, School of Mental Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email wft.0810@163.com Yan Liu, School of Public Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Youth and young adults have a high prevalence of major depressive disorder (MDD). Limited longitudinal research has explored the relationship between different dimensions of psychological stress and MDD. This study aimed to estimate the effect of psychological stress on the risk of first onset MDD in a sample of Chinese freshmen.Methods: Using a longitudinal design, 8079 Chinese first-year students were recruited at baseline, and 6985 were followed up one year later. The Psychological Stress Scale for College Students was utilized to evaluate the levels of psychological stress. MDD was evaluated using the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0). Logistic regression modeling was utilized to estimate the associations between dimensions of psychological stress and the risk of MDD.Results: Two dimensions of psychological stress, namely learning stress (OR=1.05, 95% CI:1.01– 1.09, P=0.017) and economic stress (OR=1.11, 95% CI:1.04– 1.19, P=0.001), were significantly associated with the risk of MDD. Other dimensions of psychological stress (specify family stress, interpersonal stress, intimate relationship stress, employment stress and appearance stress) were not associated with MDD.Conclusion: Psychological stress, especially learning and economic stresses, could increase the risk of MDD in university students. These factors should be incorporated into mental health prevention and intervention programs at universities to reduce the risks of MDD.Keywords: major depressive disorder, psychological stress, longitudinal study, freshmen

Lin Zhang,&ast; Yuanhang Zhang,&ast; Jin Zhou, Xiaoshuai Zhang, Lei Gao School of Health Management, Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Gao, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China, Tel +86130-9171-9592, Email hydgaolei@163.comPurpose: The primary aim of this study is to investigate the mediating role of school adaptation in the impact of adolescent bullying victimization on mental health, as well as the gender differences therein. These findings offer a novel perspective for parents and educators, aiding bullied adolescents in managing and addressing mental health concerns.Methods: The primary data source for this study was the 2020/2021 Adolescent Health Theme Database from the China Population Health Data Center (PHDA). The research sample consisted of high school students from 16 cities in Shandong Province. Descriptive statistics, reliability and validity testing, structural equation modeling, as well as mediation analysis and multiple group analysis were conducted using SPSS 26.0 and AMOS 26.0.Results: School adaptation serves as a mediating variable between adolescent bullying and mental health. The model fit indices are as follows: GFI=0.946, AGFI=0.922, RMSEA=0.070, NFI=0.978, IFI=0.979, CFI=0.97. Even when considering gender, the model still demonstrates good fit. School bullying has significant negative effects on the mental health of both male and female victims (p< 0.05). For female victims, the mitigating effect of school adaptation on mental health is slightly lower than that for males (− 2.256). Regarding cyberbullying, male victims face a greater threat to mental health (− 3.234), with a impact of − 0.109 from cyberbullying on male mental health and − 0.065 from school bullying on female mental health.Conclusion: The school is found to mediate between school bullying, cyberbullying, and mental health. Schools may play a greater role in improving female mental health than male mental health. The impact of campus bullying on female mental health is greater than that of cyberbullying, whereas the opposite is true for males. Enhancing adolescents’ school adaptation levels helps mitigate the adverse effects of school and cyberbullying on adolescent mental health.Keywords: adolescents, bullying, school adjustment, mental health

Huifang Huang,1,&ast; Kunhai Wu,2,&ast; Gaoxiang Deng,3 Yuqin Zhang3 1Intensive Care Unit, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Blood Transfusion Department, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Blood Transfusion Department, Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kunhai Wu, Blood Transfusion Department, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Tel +0086-13906921205, Email 315084702@qq.comPurpose: Blood transfusions are performed in small amounts in premature infants. Few studies have focused on the effect of the same red blood cell (RBC) package at different intervals on increasing hemoglobin(Hb) concentration. We aimed to determine the effect of infusion of the same RBC package at different time intervals on Hb levels in premature infants.Patients and Methods: Data were collected about premature infants who received the same package of RBC transfusion at two different intervals. Venous blood Hb levels before and within 24 hours after transfusion were measured for the first and second transfusions. Overall, 196 premature infants with anemia were included in the study. The data were categorized into four groups (Group I, Group II, Group III and Group IV) based on the varying intervals between transfusions of the same red blood cells.Results: Hb levels of the first and second transfusions with the same RBC package showed a significant difference pre and posttransfusion. Hb increments varied among groups: Group I (43.00 g/L), Group II (34.50 g/L), Group III (32.00 g/L), and Group IV (32.50 g/L), with Group I demonstrating a significant difference compared to Groups II, III, and IV (P< 0.05), while no differences were noted among the latter groups.Conclusion: In premature infants with anemia, hemoglobin levels significantly increased after infusion of the same RBC package at different intervals. An interval of 1 week had the most significant effect.What is New: There are differences in the effect of infusion of the same RBC at different time intervals on hemoglobin levels in premature infants. An interval of 1 week had the most significant effect.Keywords: preterm infants, interval time, transfusion, hemoglobin, RBC

Yongkang Zhang,&ast; Jiarui Liu,&ast; Yuzhen Wang, Yuan Zong, Kangli Yin, Fang Cao, Xinyu Liang, Yemin Cao Diagnosis and Treatment Center of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yemin Cao; Yongkang Zhang, Diagnosis and Treatment Center of Vascular Disease, Shanghai TCM-Integrated Hospital, No. 230 Baoding Road, Hongkou District, Shanghai, People’s Republic of China, Tel +8613361831119 ; +8613761921568, Email caoyemin@shutcm.edu.cn; zhangyongkang_tcm@163.comPurpose: Peripheral arterial disease (PAD) is a chronic ischemic disease caused by atherosclerosis of the lower extremities, with early clinical symptoms manifesting mainly as intermittent claudication. Current treatment of PAD is based on the control of cardiovascular risk factors. However, even vasoactive drugs are not ideal for improving ischemic symptoms in the lower limbs of PAD patients. Ruanjian Qingmai granules, derived from the classic formula of the late Professor Jiuyi Xi, a famous traditional Chinese medicine doctor in Shanghai, have good clinical efficacy in the treatment of the pattern of blood vessel stasis and obstruction of PAD and have been used by more than 600,000 PAD patients over the past three decades. This study aims to evaluate the efficacy and safety of Ruanjian Qingmai granules in patients with symptomatic PAD.Patients and methods: A prospective, center-randomized, double-blind, placebo-controlled clinical trial will be conducted at 9 grade A tertiary hospitals in Shanghai. It is anticipated that 250 patients with early symptomatic PAD will be recruited and randomized to the control and intervention groups (1:1 ratio of central randomization). Subjects will be treated with Ruanjian Qingmai granules or placebo at 6 g twice daily for 16 weeks. The primary efficacy indicators are the pain-free walking distance and maximum walking distance. The secondary efficacy indicators are the ankle-brachial index, walking impairment questionnaire, quality of life score, and Chinese medicine syndrome score.Conclusion: Positive results from this study will demonstrate the efficacy and safety of Ruanjian Qingmai granules in improving ischemic symptoms in patients with symptomatic PAD.Clinical Registration: This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2200056109, Date: 02/01/2022, https://www.chictr.org.cn/showproj.html?proj=150982).Keywords: peripheral arterial disease, Ruanjian Qingmai granules, intermittent claudication, efficacy, randomized controlled trial, protocol

Xia Chen,1 Jianmin Zhang,1 Yuanru Tang,1 Yan Zhang,2 Ziwen Ma,2 Yifan Hu2 1Department of Gynecology, Waitan Street Community Health Service Center, Shanghai, People’s Republic of China; 2Department of Gynecology and Obstetrics, Pudong New Area Health Care Hospital for Women and Child Gynecological Clinic, Shanghai, People’s Republic of ChinaCorrespondence: Jianmin Zhang, Email 360032800@qq.comPurpose: This study explores the link between women’s pre-pregnancy overweight and obesity and glucose and lipid metabolism in their early pregnancy. It assesses how early pregnancy glucose and lipid levels predict gestational diabetes mellitus (GDM) risk, aiming to offer foundational weight management strategies for overweight and obese women to prevent GDM.Patients and Methods: This study analyzed 2172 pregnant women from 2017 to 2021 at Waitan Street Community Health Service Center, Shanghai, monitoring early pregnancy (7– 10 weeks) glucose and lipid levels (TG, TC, HDL-C, LDL-C, FBG, HbA1c) and 24-week OGTT values. Pre-pregnancy BMI categorized participants into overweight and obese, normal, and underweight groups. We compared early pregnancy glycemic and lipid metrics and GDM incidence across groups, examining the relationship between pre-pregnancy BMI and early pregnancy blood metrics. The overweight and obese cohort was further split into GDM and non-GDM groups, comparing early pregnancy glycolipid indicators and assessing their predictive value for GDM development.Results: In the overweight and obese group, maternal FBG, HbA1c, TG, and LDL-C were higher, while HDL-C was lower than in normal and underweight groups (P< 0.05), with a higher GDM incidence (P< 0.05). Pre-pregnancy BMI positively correlated with FBG, HbA1c, TG, and LDL-C levels (r=0.556, 0.567, 0.686, 0.214; P< 0.05) but not HDL-C. Each 1-unit BMI increase raised GDM risk by 0.204 times (P< 0.05). FBG, TG, and LDL-C had high predictive accuracy for GDM in overweight and obese women, with AUCs of 0.991, 0.994, and 0.935, respectively.Conclusion: Pre-pregnancy overweight and obesity can cause early pregnancy glucose and lipid abnormalities, raising GDM risk. Early testing in such women is a strong predictor for GDM.Keywords: pregnant women, overweight and obesity, pre-pregnancy body mass index, glucose and lipid metabolism, gestational diabetes mellitus

Tiansu Lv,1,2,&ast; Jie Tian,1,3,&ast; Yaohuan Sun,1,3 Yujuan Zhang,1,2 Fang Qi,1,2 Liulan Xiang,1,2 Yutian Cao,1,2 Wenhui Zhang,1,2 Jiaxuan Huai,1,2 Yinfeng Dong,4 Xiqiao Zhou1,2 1Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiqiao Zhou; Yinfeng Dong, Email zhouxiqiao@njucm.edu.cn; dongyf@njucm.edu.cnBackground: Metabolic Associated Fatty Liver Disease (MAFLD) poses a significant threat to human health, as it can result in hepatic fibrosis and potentially progress to cirrhosis, in addition to causing a range of extrahepatic complications. The early detection of MAFLD is crucial, particularly during the initial stages when the condition may be amenable to reversal and the body composition could be vital importance.Methods: Data from participants at the Jiangsu Province Hospital of Traditional Chinese Medicine, covering the period from January 1 to December 31, 2022, were collected and subsequently randomized into training and validation cohorts. Independent risk factors for MAFLD were identified using statistical methodologies in conjunction with clinical relevance, and these factors were ultimately utilized to develop the nomogram.Results: In the training cohort, there were 356 cases of MAFLD out of a total of 513 patients, representing 71.2%, while in the validation cohort, 161 cases of MAFLD were identified out of 220 patients, accounting for 73.2%. In terms of statistical outcomes and clinical relevance, we identified a total of 12 closely related or significant variables. To enhance our understanding of the critical role of body composition parameters in predicting the incidence of MAFLD, we developed two distinct nomograms, one of which included body composition data. Notably, the nomogram that incorporated body composition demonstrated superior predictive performance, as evidenced by a well-fitted calibration curve and a C-index of 0.893 (with a range of 0.8625 to 0.9242). Furthermore, the decision curve analysis indicated that utilizing the nomogram that included body composition would yield greater benefits.Conclusion: The nomogram serves as an effective tool for predicting MAFLD. Its utility in early risk identification of MAFLD is of significant importance, as it facilitates timely intervention and treatment for patients affected by this condition.Keywords: Metabolic Associated Fatty Liver Disease, Body Composition, Nomogram

Qiang Shao,1,2,&ast; Ying Zhang,2,&ast; Zhiyuan Zhang,2 Wei Jiang,2 Yongcheng Yin,3 Yuepeng Fang,1 Ce Zhang,1 Qingfa Chen,2 Bin Ning1,2 1Cheeloo College of Medicine, Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China; 2Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ning; Qingfa Chen, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan, Shandong, 250013, People’s Republic of China, Tel +86-18866510349, Email bning@sdfmu.edu.cn; tsingfachan@163.comBackground: Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI.Methods: The T8–T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation results after injury obtained through sequencing. RNase R digestion and primer amplification experiments confirmed the circular properties of circGla. Nucleus and cytoplasm isolation experiments and FISH confirmed circGla expression in the astrocyte cytoplasm. AAV was used to establish a circGla knockdown mouse model. Behavioral tests were conducted to assess the recovery of the neurological function. The key inflammatory molecules after SCI were evaluated through MRI, RT-qPCR, and ELISA. For in vitro experiments, circGla was upregulated or knocked down in mouse astrocytes to detect its effect. The binding between miR-488 and circGla was confirmed through RIP and the dual luciferase experiment. RT-qPCR and ELISA confirmed the content correlation of the two molecules and the in vitro inflammatory function of miR-488. The binding experiment in astrocytes confirmed the binding between miR-488 and MEKK1 mRNA. Western blotting of MAPK pathway-related proteins confirmed that MEKK1 is a downstream effector for circGla and miR-488 in astrocytes.Results: Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression.Conclusion: Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1. Keywords: non-coding RNAs, inflammation, competing endogenous RNAs, traumatic spinal cord injury, secondary injury

Ya Gao,1 Shuyue Li,1 Jian Zhang,1 Yidan Zhang,1 Yuan Zhao,1 Shuming Zhang,2 Lujie Zuo,3 Guofeng Yang1 1Department of Geriatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Internal Medicine, Fuping County Hospital, Baoding, Hebei, 073200, People’s Republic of China; 3Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Guofeng Yang, Department of Geriatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email yanggf@hebmu.edu.cnBackground: Parkinson’s disease (PD) is a neurodegenerative movement disorder that impacts various systems, including the substantia nigra (SN) par compacta (SNpc) and extranigral regions like the spinal cord. The presence of persistent inflammation in the SN and spinal cord is associated with movement difficulties in PD. Atractylenolide-I (ATR-I) is a natural sesquiterpene recognized for its anti-inflammatory and neuroprotective effects. This research aimed to assess the impact of ATR-I treatment on motor function and inflammation in MPTP-induced subacute PD mice, particularly focusing on the role of ATR-I in spinal cord inflammation.Methods: The motor functions of the mice were assessed using suspension and gait tests. Dopaminergic neuronal loss in the SNpc and microglial activation in both the SNpc and spinal cord were evaluated through immunofluorescence staining. The levels of inflammatory mediators in the spinal cord were measured using RT-qPCR analysis. The expressions of SIRT1 and PGC-1α in the spinal cord were analyzed through Western blotting and RT-qPCR.Results: ATR-I treatment improved motor deficits in MPTP-induced mice. Moreover, ATR-I reduced the loss of dopamine neurons and microglial activation in the SNpc of MPTP-induced mice. Additionally, ATR-I suppressed spinal cord inflammation by decreasing microglial activation and the mRNA expression of TNF-α, IL-1β, and iNOS in MPTP-induced mice. Interestingly, ATR-I also upregulated SIRT1 and PGC-1α levels in the spinal cord of MPTP-induced mice.Conclusion: These findings suggest that ATR-I exhibits anti-inflammatory and neuroprotective properties in PD. The attenuation of spinal cord inflammation via the SIRT1/PGC-1α pathway may contribute to enhancing motor function, highlighting ATR-I as a potential therapeutic avenue for PD.Keywords: Parkinson’s disease, atractylenolide-I, spinal cord, inflammation, SIRT1, PGC‑1&#x03B1

Man Huang,1,2,&ast; Yudi Jin,3,&ast; Mengyuan Wang,2 Qiang Song,4 Yanjia Fan,1 Yu Zhang,1 Cheng Tian,1 Chi Zhang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Breast Center, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.Methods: We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.Results: Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.Conclusion: Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.Keywords: HER2-low breast cancer, neoadjuvant chemotherapy, Ki67 index, prognosis, survival

Luqian Zhan,1,&ast; Ye Zhang,2,&ast; Yanwei Li,3 Chenhui Lin,3 Heyu Zhang,3 Yuntao Liu,3 Jincai He3 1Department of Neurology, Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Third Department of Cerebrovascular Disease, Cangzhou Central Hospital, Cangzhou, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincai He; Yuntao Liu, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email hjc@wmu.edu.cn; 18267850815@163.comPurpose: Acute ischemic stroke (AIS) patients with COVID-19 have severe neurological symptoms and high mortality. It remains unclear how COVID-19 causes unfavorable outcomes. This study aimed to explore the possible mechanism focusing on inflammation and coagulation.Patients and Methods: 109 AIS patients were recruited and followed up 3 months after stroke. We used binary logistic regression to investigate if COVID-19 infection is an independent prognostic factor. To analyze the link between inflammation, coagulation, and neurological outcomes, we used mediation analysis.Results: Compared to the non-COVID-19 group, the COVID-19 group had significantly higher fibrinogen (FIB) (P < 0.001), APTT ratio (P < 0.001), D-dimer (P < 0.001), CRP (P < 0.001). Patients with unfavorable outcomes had a higher incidence of COVID-19 infection (P = 0.002), along with elevated levels of INR (P = 0.005), D-dimer (P < 0.001), and CRP (P = 0.012). The significant association between 3-month functional outcomes and COVID-19 tends to be insignificant (P = 0.294) after adding the covariates of inflammation and coagulation. The mediation analyses showed the APTT ratio mediated the association between COVID-19 and the 3-month outcome (percent mediation = 56.3%). The integrated pathway analysis implicated that the path of COVID-19 infection→CRP→APTT ratio→ 3-month outcome was significant (percent mediation = 18.7%).Conclusion: AIS with COVID-19 had a poorer prognosis. We delineated a more accurate mechanism by which COVID-19 influences functional outcomes: COVID-19 infection→inflammation→endogenous coagulation pathway→poor stroke outcome. This study provided new insight into the pathway mechanisms of AIS with COVID-19.Keywords: COVID-19, Omicron, stroke, mediation analysis, APTT ratio

Yuqi Zhang,1,2 Keqian Du,1,2 Xiaoxue Feng,1,2 Jia Xu,1,2 Peijun Xu,1,2 Jianlin Huang1,2 1Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Jianlin Huang; Peijun Xu, Department of Rheumatology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China, Email hjianl@mail.sysu.edu.cn; xupj@mail.sysu.edu.cnPurpose: This study aimed to compare the rates of disease remission evaluated using various remission criteria, including Boolean2.0, Boolean1.0, clinical disease activity index (CDAI), simplified disease activity index (SDAI), and disease activity score using 28 joints based on C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA).Patients and Methods: A cross-sectional observational analysis was performed using data from patients with RA enrolled in a smart system of disease management group (SSDM). The clinical remission rates of RA patients estimated using the DAS28-CRP, CDAI, SDAI, Boolean1.0 and Boolean2.0 criteria were investigated. Variables were compared using the t-test, Mann–Whitney U-test, or chi-squared test. The agreement between Boolean remission and the DAS28-CRP, CDAI, or SDAI definitions of remission was assessed using McNemar’s test with k coefficient of agreement.Results: A total of 5619 patients were included in the analysis. The mean age of the patients was 56.33 (± 13.01) years, with the majority being female (4491, 79.9%). The rates of remission, as assessed by Boolean2.0, Boolean1.0, DAS28-CRP, CDAI, and SDAI, were 16.6%, 9.7%, 35.2%, 9.1%, and 9.4%, respectively. Comparison with Boolean1.0 criteria revealed higher concordance between Boolean2.0 and DAS28-CRP remission and lower concordance with CDAI and SDAI, regardless of whether the analysis was conducted on the entire population or subgroups based on gender, age or disease duration. Additionally, the administration of different medications may have influenced the rate of Boolean2.0 remission.Conclusion: This study demonstrated a higher concordance between Boolean2.0 criteria and DAS28-CRP remission and a lower concordance with CDAI and SDAI when compared with Boolean1.0 remission criteria.Keywords: Boolean, clinical disease activity index, concordance, disease activity score using 28 joints, remission, simplified disease activity index

Mengyao Shi,1,&ast; Xueyu Mao,2,&ast; Xuechun Wu,2 Min Chu,2 Huicong Niu,2 Lulu Sun,1 Xinyue Chang,1 Yu He,1 Yi Liu,1 Daoxia Guo,3 Yonghong Zhang,1 Zhengbao Zhu,1 Jing Zhao2,4 1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 4Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China, Email zhao_jing@fudan.edu.cn Zhengbao Zhu, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, People’s Republic of China, Email zbzhu@suda.edu.cnBackground: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.Keywords: prealbumin, ischemic stroke, prognosis, cohort study

Caixing Shi,1 Yueyao Li,2 Zhidong You,3 Yiran Tian,4 Xiaoyu Zhu,4 Hao Xu,4 Menghan Yang,4 Yutong Zhang,4 Rui Dong,4 Huirong Quan,4 Yongyi Shang,4 Xiaojin Li1 1School of Basic Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 2College of Integrated Chinese and Western Medicine, Jining Medical University, Jining, 272067, People’s Republic of China; 3School of Nursing, Jining Medical University, Jining, 272067, People’s Republic of China; 4School of Clinical Medicine, Jining Medical University, Jining, 272067, People’s Republic of ChinaCorrespondence: Xiaojin Li, School of Basic Medicine, Jining Medical University, No. 133 hehua Road, Taibai Lake New District, Jining, 272067, People’s Republic of China, Tel +8615265775150, Email jinli10221@163.comPurpose: Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro.Materials and Methods: The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms.Results: MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1β in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells.Conclusion: CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation.Keywords: mangiferin, liver injury, oxidative stress, inflammation, Nrf2

Xinchen Wang,1,&ast; Haiwei Bu,1,2,&ast; Chen Wei,1 Jingyi Liu,1– 3 Yuewen Qi,3,4 Weichao Shan,1– 3 Ying Zhang,1– 3 Lixian Sun1– 3 1Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China; 2The Cardiovascular Research Institute of Chengde, Chengde, People’s Republic of China; 3Hebei Key Laboratory of Panvascular Diseases, Chengde, People’s Republic of China; 4Central Laboratory of The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixian Sun, Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, China, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, Hebei Province, People’s Republic of China, Tel +86 0314 227 9016, Fax +86 0314 227 4895, Email lixiansun01@126.comPurpose: To elucidate the predictive values of adipocytokines in patients with acute coronary syndrome (ACS).Patients and Methods: Overall, 297 patients with ACS were consecutively enrolled in this prospective cohort study between June 2015 and July 2017 and completed follow-up with a median follow-up time of 6.5 years. For consistency, the last visit date was June 20, 2023. Serum levels of retinol-binding protein-4 (RBP4), interleukin-1β (IL-1β), monocyte chemoattractant protein 1(MCP-1), adrenomedullin (ADM), netrin 1 (NTN 1), and omentin were measured using enzyme-linked immunosorbent assay. Follow-up data were collected during clinical visits or through telephone interviews at 1, 3, 6, 12 months, and annually. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including all-cause mortality, rehospitalization for percutaneous coronary intervention, and severe angina requiring rehospitalization.Results: All biomarkers displayed a good diagnostic ability of MACEs. The Kaplan–Meier curve showed that the cumulative survival rates of high level of RBP4, IL-1β, and MCP-1 and low level of the ADM, NTN1, and omentin had lower cumulative survival rates (Log rank tests: all p< 0.05). After adjustment in the Cox hazard proportional model, the results were RBP4 ≥ 6.87 ng/mL, hazard ratio (HR)=2.512, p=0.003; IL-1β≥ 58.95 pg/mL, HR=3.809, p< 0.001; MCP-1 ≥ 401.75 pg/mL, HR=4.047, p< 0.001; ADM≤ 120.01 ng/mL, HR=3.930, p=0.008; NTN1 ≤ 63.7 pg/mL, HR=3.345, p=0.007; omentin ≤ 4.54 ng/mL, HR=2.830, p=0.004. P-values for interaction were > 0.05 in the sex, age, and dyslipidemia subgroups.Conclusion: Pro-inflammation adipocytokines RBP4, IL-1β, and MCP-1 increased and anti-inflammation biomarkers ADM, NTN1, and omentin decreased were independently associated with a higher risk of MACEs in patients with ACS.Keywords: acute coronary syndrome, adipocytokines, prognosis