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Jia Zhou,1,* Wenwen Wang,1,* Qiyu Zhang,1,* Hanlin Zhang,1 Keyun Tang,1 Chenhui Mao,2 Mingli Li,3 Jun Li1 1Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China; 2Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Li, Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Disease, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-010-69151500, Fax +86-010-69151502, Email lijun35@hotmail.comPurpose: Syphilis, caused by Treponema pallidum, presents a diagnostic challenge due to its diverse clinical manifestations. Neurosyphilis has seen a resurgence in recent years, particularly among men who have sex with men and those living with HIV. Diagnosis of neurosyphilis in emergency settings is challenging due to its varied neurological presentations. This study aims to serve as a reference for dermatologists and neurologists in diagnosing and treating neurosyphilis.Patients and Methods: This retrospective study analyzed patients who presented with neuropsychiatric symptoms and were ultimately diagnosed with neurosyphilis. These patients were collected from the emergency department in Peking Union Medical College Hospital between January 2018 and November 2023. The medical history, clinical symptoms, laboratory examinations, cranial MRI characteristics, and treatment regimens of these patients were investigated.Results: Among the included 12 neurosyphilis patients, memory deterioration was observed in 8 out of the 12 neurosyphilis patients. Diagnosis often resulted in delays, with misdiagnoses mainly including Alzheimer’s disease, stroke, and epilepsy. Neuroimaging revealed various abnormalities, predominantly affecting ventricular and temporal regions. Treatment with penicillin-based regimens varied in compliance, with only a minority of patients adhering to guidelines. Treatment outcomes were inconsistent, with some patients experiencing irreversible neurological damage and fluctuating serum rapid plasma reagin (RPR) titers.Conclusion: Diagnosis of neurosyphilis in the emergency department remains challenging, necessitating awareness of its varied neurological presentations. Enhanced diagnostic strategies are imperative to accelerate treatment initiation and improve outcomes for affected individuals.Keywords: neurosyphilis, emergency department, neuropsychiatric symptoms, cerebrospinal fluid, serologic tests

Ya-Ya Bai,1 Rui Tian,1 Yan Qian,2 Qiao Zhang,1 Chong-Bo Zhao,1 Yong-Gang Yan,1 Li Zhang,3 Shi-Jun Yue,4 Yu-Ping Tang1 1Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 2Suzhou Institute for Drug Control, Suzhou, Jiangsu Province, 215000, People’s Republic of China; 3Hanlin College, Nanjing University of Chinese Medicine, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 4International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, 050200, People’s Republic of ChinaCorrespondence: Qiao Zhang, Shaanxi University of Chinese Medicine, Shiji Avenue, Xi Xian New District, Xi’an, 712046, People’s Republic of China, Tel +86-15895973680, Fax: +86-02938185061, Email 18700081184@163.comBackground: Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown.Objective: This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics.Methods: Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites.Results: Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect.Conclusion: PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application. Keywords: gut microbiota, metabolomics, wine steaming, diarrhea, rhubarb

Maolin Hou,1,* Jinghua Chen,2,* Le Yang,3,* Lei Qin,3 Jie Liu,4 Haibo Zhao,5 Yujin Guo,6 Qing-Qing Yu,6 Qiujie Zhang5 1Department of Internal Medicine, Siziwangqi People’s Hospital, Wulancabu, 011800, People’s Republic of China; 2Department of Oncology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250000, People’s Republic of China; 3Department of Gastrointestinal Surgery, Jining, 272000, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, People’s Republic of China; 5Department of Oncology, Jining, 272000, People’s Republic of China; 6Department of Clinical Pharmacology, Jining, 272000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiujie Zhang, Department of Oncology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email zhangqiujie86@163.com Qing-Qing Yu, Department of Clinical Pharmacology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email yuqingqing_lucky@163.comIntroduction: Gastric cancer, the fifth most common malignant tumor in the world, poses a serious threat to human health. However, the role of fatty acid metabolism (FAM) in gastric cancer remains incompletely understood. We aim to provide guidance for clinical decisions by utilizing public database of gastric adenocarcinoma to establish an FAM-related gene subtypes via machine learning algorithm.Methods: The intersection of FMGs from KEGG, Hallmark, and Reactome bioinformatics databases and the DEGs of the TCGA-STAD cohort was used to decompose the gene matrix related to establish FAM-related gene subtypes by NMF. Comparison of immune infiltrating differences between subtypes using ESTIMATE and Cibersort algorithms. The multifactor Cox regression to identify independent risk genes for patient prognosis based on the subtypes. A prognostic model including independent risk genes was built using random survival forest and Cox regression. IHC validation in gastric cancer and adjacent tissues confirmed the above gene expression level.Results: 71 DEGs related to FMGs of STAD were identified, which was used to established the FAM-related gene subtypes, C1 and C2. The immune infiltrating analysis showed that most immune features of C2 were significantly upregulated compared to C1. The independent risk genes were CGβ 8, UPK1B, and OR51G based on the subtypes. A gastric cancer prognostic model consisting of independent risk genes was constructed and patients were classified into high-risk and low-risk groups with survival differential analysis. Finally, IHC showed that CGβ 8 and UPK1B expression were upregulated in gastric cancer, while OR51G2 did not detect differences in expression.Conclusion: The study developed a machine learning-based gastric cancer prognosis risk model using FMGs. This model effectively stratifies patients according to their risk levels and provides valuable insights for clinical decision-making, enabling accurate evaluation of patient prognosis.Keywords: Gastric cancer, fatty acid metabolism-related genes, machine learning, genomics, signature

Jiamin Mao,1,2 Xiaoyuan Liu,2 Lie Zhang,1 Yu Chen,2 Shiyu Zhou,2 Yujiao Liu,2 Jing Ye,2 Xiaohong Xu,2 Quan Zhang1– 4 1Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 2Sichuan Higher Education Institute Key Laboratory of Structure-Specific Small Molecule Drugs, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 3Development and Regeneration Key Laboratory of Sichuan Province, Department of Anatomy and Histoembryology, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 4Chengdu Nature’s Grace Biological Technology Co., Ltd., Chengdu, 610213, People’s Republic of ChinaCorrespondence: Quan Zhang, Email zhangquancdmc@126.comPurpose: Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR’s effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR’s solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism.Methods: The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms.Results: After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects.Conclusion: MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.Keywords: Morin, self-nanoemulsifying drug delivery system, acute alcohol intoxication, oral bioavailability, alcohol-induced tissue injury

Qiuli Zhang, Jianmin Chang Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jianmin Chang, Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 10-85133303, Email changjianmin@medmail.com.cnAbstract: Linear epidermal nevus is a congenital focal epidermal dysplasia common at birth or during childhood. Linear epidermal nevus followed by cutaneous malignancy is extremely rare. Here, a case of linear epidermal nevus followed by eccrine porocarcinoma (EPC) is reported.Keywords: linear epidermal nevus, eccrine porocarcinoma

Mengmeng Ji,1,* Xiao Ran,2,3,* Houjuan Zuo,1 Qin Zhang4 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Critical-Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Zhang, Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People’s Republic of China, Tel +86-15717154768, Email qzhang8@tjh.tjmu.edu.cn Houjuan Zuo, Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People’s Republic of China, Tel +86-83663280, Email zuohoujuan@126.comAbstract: Fulminant myocarditis (FM) is characterized by rapid cardiac deterioration often instigated by an inflammatory cytokine storm. The kallikrein–kinin system (KKS) is a metabolic cascade known for releasing vasoactive kinins, such as bradykinin-related peptides, possessing diverse pharmacological activities that include inflammation, regulation of vascular permeability, endothelial barrier dysfunction, and blood pressure modulation. The type 1 and type 2 bradykinin receptors (B1R and B2R), integral components of the KKS system, mediate the primary biological effects of kinin peptides. This review aims to offer a comprehensive overview of the primary mechanisms of the KKS in FM, including an examination of the structural components, regulatory activation, and downstream signaling pathways of the KKS. Furthermore, it explores the involvement of the tissue kallikrein/B1R/inducible nitric oxide synthase (TK/B1R/iNOS) pathway in myocyte dysfunction, modulation of the immune response, and preservation of endothelial barrier integrity. The potential therapeutic advances targeting the inhibition of the KKS in managing FM will be discussed, providing valuable insights for the development of clinical treatment strategies. Keywords: fulminant myocarditis, Kallikrein–Kinin system, inducible nitric oxide synthase, nitric oxide, inflammatory

Xiao-Fang Dong,1 Qiang Zhang,2 Jia-Ning Wei,2 Qian-Yu Zhou,3 Fan-Jia-Yi Yang,2 Yan-Jin Liu,4 Yu-Sheng Li,5 Chang-Qing Sun2,3 1Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Epidemiology and Biostatistics, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chang-Qing Sun, School of Nursing and Health, Zhengzhou University, NO. 101 Kexue Road, High-Tech Development Zone of District, Zhengzhou, Henan, People’s Republic of China, Email suncq@zzu.edu.cnObjective: Our research explores how leisure-time sedentary behavior (SB) correlates with stroke risk. Additionally, we utilize the isotemporal substitution model (ISM) to examine how replacing brief durations of leisure-time SB with light physical activity (LPA), moderate physical activity (MPA), vigorous physical activity (VPA), and sleep might influence the risk of stroke.Methods: This investigation tracked 478,198 participants from the UK Biobank. Data regarding individual leisure-time SB and PA were collected through a standardized questionnaire. A Cox proportional hazards model, alongside an isotemporal substitution model (ISM), was utilized.Results: We identified 10,003 cases of incident stroke over 12.7 years. When compared to participants who engaged in leisure-time SB for less than 4 hours per day, the hazard ratios (HRs) for stroke incidence increased with more prolonged leisure-time SB: HRs were 1.06 (95% CI: 1.01 to 1.11) for 4– 6 h/d, 1.16 (95% CI: 1.10 to 1.23) for 6– 8 h/d, and 1.24 (95% CI: 1.15 to 1.33) for over 8 h/d. According to the ISM analysis, substituting leisure-time SB with various forms of PA could markedly reduce stroke risk. For individuals sleeping ≤ 8h/d, replacing one hour of leisure-time SB with an equivalent duration of LPA, VPA, or sleep corresponded to a 3.0%, 7.0%, and 22.0% decrease in stroke risk, respectively. Meanwhile, for those already sleeping more than 8h/d, substituting one hour of leisure-time SB with an equivalent duration of LPA or VPA resulted in a notable decrease in the risk of stroke by 6.0% and 18.0%, respectively.Conclusion: The findings demonstrate that leisure-time SB and unhealthy sleep durations are confirmed risk factors for stroke. For individuals sleeping 8 hours or less per day, and for those who sleep more than 8 hours, substituting SB with an adequate amount of sleep or engaging in VPA, respectively, emerges as an effective strategy for reducing stroke risk.Keywords: stroke, isotemporal substitution model, physical activity, sedentary behavior, sleep

Lanqi Yu,1,2 Xiaolu Wu,1,2 Qinhan Zhang,1,2 Binghai Sun1,2 1School of Psychology, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Intelligent Laboratory of Child and Adolescent Mental Health and Crisis Intervention of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of ChinaCorrespondence: Qinhan Zhang; Binghai Sun, School of Psychology, Zhejiang Normal University, 688 YingBin Road, Jinhua, Zhejiang, People’s Republic of China, Email Qinhanzhang@zjnu.edu.cn; jky18@zjnu.cnPurpose: Within the scope of secondary education, social adjustment among students signifies their ability to effectively engage in social activities and adapt to shifting social environments. Extensive research across diverse geographical and sociocultural landscapes has demonstrated a positive correlation between social support and social adjustment; nonetheless, the specific mechanisms that facilitate this correlation among secondary school students remain largely unexplored. This study examines the roles of subjective well-being and psychological resilience as potential mediators in the connection between social support and social adjustment.Participants and Methods: To achieve this, a descriptive correlation design was employed with four measures, including Social Support Scale, Social Adjustment Diagnosis Scale, Adolescent Students’ Life Satisfaction Scale, and the Chinese version of Mental Toughness Inventory (MTI). A total of 1537 valid responses from secondary school students across Zhejiang province (China) were collected, of which 786 were boys (51.1%) and 751 girls (48.9%), with average age of 16.89 years (SD = 0.79).Results: This research demonstrates that social support, along with subjective well-being and psychological resilience, significantly and positively influences social adjustment. It was observed that both subjective well-being and psychological resilience, whether occurring simultaneously or in succession, partially mediate the influence of social support on social adjustment.Conclusion: The implications of this research suggest that enhancing social adjustment among secondary school students can be achieved by increasing their levels of social support, thereby boosting subjective wellbeing and fortifying psychological resilience. Within the environment of secondary schools, augmenting social support leads to improved social adjustment; furthermore, enhancing subjective wellbeing and reinforcing psychological resilience are crucial for supporting students’ positive adaptation to dynamic social environments. Teachers and educational policymakers could implement training programmes, provide psychological counselling, and bolster home-school collaboration as strategies to foster better social adjustment among students. Keywords: social support, social adjustment, subjective well-being, psychological resilience, Chinese

Kangpeng Li, Qiang Zhang Department of Orthopedics, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qiang Zhang, Email ditanzq@163.com

Meng Zheng,1 Chongfang Meng,2 Qi Zhang,3 Xiang Yan,1 Na Li1 1Dermatology Department of the First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunan, People’s Republic of China; 3Nursing Department of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Na Li, Dermatology Department of the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Wuhua District, Kunming, Yunnan, People’s Republic of China, Email 4845878@qq.comObjective: This study aims to systematically search, screen, evaluate, and synthesize evidence related to discharge preparation for elderly chemotherapy patients, providing an evidence-based reference for implementing discharge preparation services for this demographic.Methods: Systematic searches were conducted on databases including BMJ Best Clinical Practice, JBI Library, UpToDate Clinical Advisor, Cochrane Library, and relevant guideline websites. The collected literature comprised thematic summaries, clinical practice guidelines, technical reports, expert consensus, and systematic reviews related to discharge preparation for elderly chemotherapy patients. Relevant evaluation tools were selected based on the type of literature to assess methodological quality, and the evidence was extracted, summarized, and organized.Results: Fifteen pieces of evidence were selected according to inclusion and exclusion criteria, including one clinical decision, two expert consensuses, six systematic reviews, two meta-analyses, and four guidelines. Twenty-nine pieces of evidence were summarized across four domains: assessment, planning, implementation, and evaluation.Conclusion: The summarized evidence provides a reliable basis for implementing evidence-based discharge preparation services for elderly chemotherapy patients, laying a foundation for future clinical practice applications. Based on the evidence content and relevant literature, this paper explores the screening and evaluation tools applicable for use in clinical practice.Keywords: elderly, chemotherapy, discharge preparation, evidence-based nursing, evidence synthesis, review

Xiwen Yin,1,&ast; Qiang Zhang,1,&ast; Yuting Wang,1 Bilin Tao,1 Xiaolong Zhang,2 Jinyan Shi,3 Xiaowei Deng,1 Jianming Wang1,4,5 1Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China; 2Department of Tuberculosis Control, Center for Disease Control and Prevention, Suzhou, 215000, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 4Department of Tuberculosis, The Third People’s Hospital of Changzhou, Changzhou, 215000, People’s Republic of China; 5National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianming Wang, Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China, Tel +86-25-86868414, Email jmwang@njmu.edu.cnPurpose: Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China.Patients and Methods: We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains.Results: After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63– 4.49, P< 0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20– 2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases.Conclusion: There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.Keywords: tuberculosis, transmission, cluster, whole genome sequencing, spatial analysis

Jinghui Zhang,1 Mowei Liu,2 Qing Zhang,1 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Department of Psychology, Trent University, Peterborough, ON, CanadaCorrespondence: Yan Li, Email liyan@shnu.edu.cnPurpose: This study investigates the relationship between mother phubbing and preschoolers’ problematic media use, examining the mediating role of the mother-child relationship and the moderating effects of paternal coparenting. Drawing on the Interactive Theory of Childhood Problematic Media Use and family system theory, we aim to identify key family dynamics that influence early childhood media habits. The findings could provide insights into mitigating the negative impacts of parental phubbing on children’s media habits and inform targeted interventions to promote healthier media use among young children.Methods: The study examined 1008 mothers (Mage = 35.58 years, SD = 3.90) with preschool-aged children (Mage = 4.59 years, SD = 0.92) who completed self-report questionnaires. Path analysis with bootstrap sampling was executed to assess the moderated mediation model.Results: Mother phubbing was positively associated with preschoolers’ problematic media use, with this relationship mediated by the mother-child relationship. Paternal coparenting moderated both the direct and indirect pathways in this relationship. Specifically, paternal coparenting directly mitigated the impact of mother phubbing on child problematic media use. Additionally, it alleviated the negative influence of mother phubbing on the mother-child relationship, thereby indirectly reducing its adverse effect on preschoolers’ problematic media use. Overall, paternal coparenting demonstrated a protective function against the negative consequences of mother phubbing.Conclusion: The findings significantly contribute to our understanding of how mother phubbing might increase the risk of problematic media use among preschoolers and underscore the potential importance of reducing mother phubbing and increasing paternal coparenting as integral steps to prevent preschoolers’ problematic media use.Keywords: mother phubbing, mother-child relationship, problematic media use, paternal coparenting, preschoolers

Minjing Liu,1,2,&ast; Jiaojiao Li,2,&ast; Jing Xu,2 Ya Chen,2 Chiafu Chien,3 Hui Zhang,4 Qing Zhang,5 Li Wang2 1Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4School of Nursing, Suzhou Vocational Health College, Suzhou, People’s Republic of China; 5Physical Education and Sports School, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, School of Nursing, Suzhou Medical College, Soochow University, No. 1 Shi zi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Email li-wang-1@suda.edu.cn Qing Zhang, Physical Education and Sports School, Soochow University, Suzhou, People’s Republic of China, Email zhangqing@suda.edu.cnPurpose: This randomized parallel controlled trial aimed to determine the effectiveness of graded progressive home-based resistance combined with aerobic exercise in improving physical fitness in community-dwelling older adults with sarcopenia.Patients and Methods: Community-dwelling older adults (≥ 60 years) with sarcopenia were randomly assigned to the intervention group (IG), receiving 12 weeks of graded progressive home-based resistance and aerobic exercise training, and the control group (CG), maintaining lifestyle unchanged. The primary outcomes were knee extensor muscle strength and the six-minute walk distance (6MWD). Intention-to-treat analysis was applied to the data from all participants in the CG and IG. Post-intervention differences between the intervention and control groups were determined using a generalized estimated equation model with pre-values adjusted.Results: Data from all the participants in the IG (n=41) and CG (n=45) were analyzed. After the intervention, knee extensor muscle strength (95% CI: 0.140– 3.460, P=0.036), 6MWD (95% CI: 35.350– 80.010, P< 0.001), flexor muscle strength and the results of 30s bicep curls, 30s chair stand, the chair sit and reach test and back stretch test in the IG were larger and value of the timed up-and-go test was smaller than those in the CG (P< 0.05). The body composition, quality of life and their changes showed no group differences. The attendance rates were 82.9% and 85.4% for resistance and aerobic exercise, respectively.Conclusion: The 12-week graded progressive home-based resistance and aerobic exercise intervention improved muscle strength, balance, flexibility, and cardiorespiratory fitness in community-dwelling older adults with sarcopenia, whereas body composition and quality of life remained unchanged. The research was approved by the Ethics Committee of Soochow University (ECSU-2019000161) and registered at the Chinese Clinical Trial Registry (ChiCTR1900027960, http://www.chictr.org.cn/showproj.aspx?proj=45968).Keywords: physical function, muscle strength, multicomponent exercise, walking, skeletal muscle disease

Lin Zhu,1 Qian Zhang,1 Ke Ni,2 Xue-Jun Yang,1 Kai Jin,3 Wei Wei,4– 6 David A Preece,7,8 Bao-Ming Li,1,9 Xin-Lu Cai1,9 1Institute of Brain Science and Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Qiqihar Mental Health Center, Qiqihar, People’s Republic of China; 3The Fifth People’s Hospital of Lin’an District, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, People’s Republic of China; 6NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, People’s Republic of China; 7School of Population Health and Curtin enAble Institute, Curtin University, Perth, WA, Australia; 8School of Psychological Science, The University of Western Australia, Perth, WA, Australia; 9Zhejiang Philosophy and Social Science Laboratory for Research in Early Development and Childcare, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Xin-Lu Cai, Institute of Brain Science and Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Tel +86 571-28864320, Email caixinlu@hznu.edu.cnBackground: Abnormalities of regulating positive and negative emotion have been documented in patients with mental disorders. Valid and reliable psychological instruments for measuring emotion regulation across different valences are needed. The Perth Emotion Regulation Competency Inventory (PERCI) is a 32-item self-report measure recently developed to compressively assess emotion regulation ability across both positive and negative valences.Purpose: This study aimed to validate the Chinese PERCI in a large non-clinical sample and examine the clinical utility in patients with major depressive disorder (MDD).Methods: The Chinese PERCI was administered to 1090 Chinese participants (mean age = 20.64 years, 773 females). The factor structure, internal consistency, test-retest reliability, convergent validity, concurrent validity, and predictive validity were examined. Moreover, a MDD group (n = 50) and a matched healthy control group (n = 50) were recruited. Group comparisons and the linear discriminant analysis were conducted to assess the clinical relevance of the PERCI.Results: Confirmatory factor analysis supported the intended eight-factor structure of the PERCI in the Chinese population. The PERCI showed high internal consistency, test-retest reliability, as well as good convergent and concurrent validity. The MDD group had significantly higher PERCI scores than the healthy control group. Linear discriminant function comprised of the eight factors successfully distinguish patients with MDD from their matched controls.Conclusion: The Chinese version of the PERCI is a valid and reliable instrument to compressively measure emotion regulation across positive and negative valences in the general Chinese population and patients with depression.Plain Language Summary: The Perth Emotion Regulation Competency Inventory was designed to comprehensively assess emotion regulation ability across both positive and negative valences. This study provided the first translation and psychometric evaluation of the PERCI in the Chinese context. The findings support that the Chinese version of the PERCI is a reliable and valid measurement for assessing emotion regulation across positive and negative valences in research and clinical practice.Keywords: emotion regulation, reliability, validity, factor structure, depression

Qing Zhang,1,2,&ast; Xiaowen Liang,1,2,&ast; Zhiyi Chen1– 3 1Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 2Institute of Medical Imaging, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China; 3Department of Medical Imaging, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyi Chen, Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, the Affiliated Changsha Central Hospital, 161 Shaoshan Road, Changsha, 410004, Hunan, People’s Republic of China, Email zhiyi_chen@usc.edu.cnAbstract: There is a growing trend towards minimally invasive or noninvasive alternatives for gynecological disorders due to their rapid alleviation of symptom, expedited recovery, and minimal risks of postoperative complications. Thermal ablation technology has been commonly advocated as a minimally invasive therapeutic methods in recent years, including microwave ablation, radiofrequency ablation, and high-intensity focused ultrasound. The increasing application scenarios require updated and systematic research, and more evidence to promote their appropriate use. The objective of this review is to summarize the latest views of ablation from a prospective of fertility protection, endeavor to clarify the clinical value of thermal ablation technology in protecting fertility by assessing parameters such as ablation rates, alleviation of disease symptoms, re-intervention rates and post-treatment pregnancy rates. We review the clinical studies of ablation for uterine fibroids and adenomyosis treatment in the past 10 years, summarize the limitation and the prospects of its development in the treatment process, so as to provide clinicians with advice on the best practice. In the management of uterine fibroids and adenomyosis, thermal ablation technology offers improved fertility preservation and minimizes normal tissue injury compared to traditional surgical approaches for patients pursuing reproductive goals. In the future, thermal ablation technology will play a significantly enhanced role in preserving fertility for individuals requiring treatment for uterine fibroids and adenomyosis, guided by indications. But further research is still needed in the form of more extensive randomized prospective trials to provide stronger evidence supporting this perspective.Keywords: fertility protection, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound, uterine fibroids, adenomyosis

Yuanzhong Fang,1 Juan Jin,1 Minfei Peng,2 Lidong Xu,1 Linyuan Gu,1 Danni Bao,3 Qiuying Zhang,4 Kainan Jin5 1Department of Clinical Laboratory, Hangzhou Linping District Women & Children Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China; 3Department of Clinical Laboratory, Sanmen People’s Hospital, Sanmen Bay Branch of The First Affiliated Hospital, Zhejiang University School of Medicine, Taizhou, Zhejiang, 317100, People’s Republic of China; 4Department of Clinical Laboratory, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 5Department of Gastroenterology, Linhai First People’s Hospital, Taizhou, Zhejiang, 317000, People’s Republic of ChinaCorrespondence: Qiuying Zhang, Department of Clinical Laboratory, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China, Email 26067889@qq.com Kainan Jin, Department of Gastroenterology, Linhai first People’s hospital, Taizhou, Zhejiang, 317000, People’s Republic of China, Email 353803262@qq.comBackground: Hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP) has been spreading rapidly worldwide. Here, we investigated the genomic characteristics of ST11 K. pneumoniae isolate SM117 with capsular serotype KL25, co-carrying blaNDM-5, two copies of blaKPC-2 and multiple plasmid-borne virulence genes from a county level hospital in China.Methods: Antimicrobial susceptibility of K. pneumoniae SM117 was evaluated. The Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms were applied to sequence the genome and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, antibiotic resistance genes, plasmid replicon types and virulence genes. The phylogenetic analysis was performed based on the core genome single nucleotide polymorphisms (cgSNPs) using CSI Phylogeny 1.4, and further visualized by Interactive Tree of Life (iTOL) V5 web server.Results: The whole-genome sequence of K. pneumoniae SM117 is made up of eight contigs totaling 6,104,486 bp, contain a 5,612,620 bp single chromosome and seven plasmids. The isolate was assigned to ST11 with capsular serotype KL25, co-carrying including blaNDM-5, blaKPC-2 and multiple plasmid-borne virulence genes including rmpA2 and aerobactin genes iucABCD-iutA. The coexistence of blaKPC and blaNDM in K. pneumoniae strains exhibit a high degree of resistance to β-lactam antibiotics. The strain SM117 also carries multiple antibiotic resistance genes, making it resistant to all antibiotics except polymyxin. The closest relative of K. pneumoniae C793 was identified in 2023 from a hospital surface sample in Zhejiang, China, with just 52 SNPs difference.Conclusion: This study reported the genomic characteristics of a multidrug-resistant ST11 K. pneumoniae with capsular serotype KL25, co-carrying blaNDM-5, two copies of blaKPC-2 genes and multiple plasmid-borne virulence genes in China. These findings will provide important knowledge of the antibiotic resistance mechanisms, genomic epidemiological characteristics and transmission dynamics of multidrug-resistant K. pneumoniae.Keywords: whole-genome sequencing, K. pneumoniae, multidrug-resistance, blaNDM-5, blaKPC-2, rmpA2, iucABCD-iutA, hvCRKP

Pan Luo, Dejin Gao, Chenglong Wang, Rui Guo, Qingguo Zhang Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Qingguo Zhang; Rui Guo, Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, People’s Republic of China, Email plastic369@163.com; guorui0114@163.comBackground: The primary aim of this study was to explore whether sex hormones affect the occurrence of basal cell carcinoma (BCC) from a genetic perspective using a two-sample Mendelian randomization (MR) study.Methods: Exposure and outcome data for this MR analysis were derived from previously published GWAS studies. In this study, estradiol, sex hormone-binding globulin (SHBG), bioavailable testosterone, and total testosterone were used as exposures, and BCC was used as the outcome for the two-sample MR analysis. The random effects inverse variance weighted (IVW) model was the primary analytical model, and the simple mode, weighted median, MR-Egger, and weighted mode methods were applied as complementary approaches. Furthermore, the “leave-one-out” sensitivity analysis was performed to assess stability, Cochran’s Q test to evaluate heterogeneity, and the MR-Egger intercept test to analyze horizontal multiplicity.Results: The two-sample MR analysis of the sex hormone and BCC showed that estradiol, sex hormone-binding globulin (SHBG), bioavailable testosterone, and total testosterone were not a causal factor in BCC (P> 0.05). The results of the heterogeneity test and horizontal pleiotropic analysis showed that no heterogeneity or horizontal pleiotropic existed in all MR analyses (Cochran’s Q-P> 0.05, Egger intercept-P> 0.05).Conclusion: The two-sample MR analysis showed that estrogen and testosterone did not affect the occurrence and development of BCC at the genetic level.Keywords: sex hormone, basal cell carcinoma, Mendelian randomization study, genetics, causal relationship

Qingbao Guo,1,2,&ast; Manli Xie,3,&ast; Qian-Nan Wang,4,&ast; Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Qingqing Shen,1– 3,&ast; Qing Zhang,2,3,&ast; Yunxiao Liu,1– 3,&ast; Yingao Cui,1– 3 Jingwen Shang,1– 3 Xiaoping Yuan,2,3 Feng Geng,4 Liang Sun,5 Zhiwei Liu,5 Rongchun Yang,5 Kai Zhang,2,3 Huanzhong Liu2,3,6 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Psychiatry, Fuyang Third People’s Hospital, Fuyang, Anhui, People’s Republic of China; 6Brain Bank Construction and Resource Utilization, Anhui Provincial Key Laboratory, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang; Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zhangkai@ahmu.edu.cn; huanzhongliu@ahmu.edu.cnPurpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls.Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects’ suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed.Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P< 0.001), and the pain intensity in the MDD group (3.77± 2.48) was significantly higher than the Control group (0.617± 0.99) (P < 0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation.Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.Keywords: adolescents, depressive disorder, pain intensity, pain sensitivity, suicidal ideation

Qiaolin Zhang,1,&ast; Zhu Mei,2,&ast; Lan Wei,1 Dong Liu,1 Chengbing Xie,1 Yongzhu Xu1 1Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongzhu Xu, Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China, Email xucqbc123@126.comObjective: Hepatitis B virus (HBV) infection is a significant global public health concern, with variable prevalence rates across regions. The prevalence of transfusion-transmitted HBV infection (TT-HBV) via donated blood necessitates an evaluation of blood safety and potential risks to the population. This study assessed the prevalence of HBV infection among blood donors in Southwestern China over 6 years.Methods: We analyzed 903,023 blood donations from a central blood center in Southwestern China between January 2017 and December 2022. The prevalence of HBV in donations was determined for one-time and repeat donors, considering birth cohorts and covariates. Demographic characteristics, donation frequency, and anti-HBV antibody status were analyzed to estimate the incidence of TT-HBV.Results: One-time donors provided 47.78% of the samples, and 52.22% were from repeat donors. The HBV prevalence decreased from 1.0% in 2017 to 0.87% in 2022 in one-time donors and from 0.30% to 0.09%, respectively, in repeat donors. A significantly lower HBV prevalence was identified in the post-1992 birth cohort (0.33%) than in the pre-1992 birth cohort (1.67%). The estimated incidences of TT-HBV occurring from one-time donors, repeat donors, post-1992 birth cohort donors, and pre-1992 birth cohort donors were 20.76, 13.84, 0.82, and 20.98 per 104 person-years, respectively.Conclusion: Our findings indicate a decreasing trend in HBV prevalence among blood donors in Southwestern China over the 6-year study period. This decline may be attributed to the widespread administration of HBV vaccinations and stringent screening measures implemented by blood donation centers. Continuous monitoring for HBV among blood donors is necessary to evaluate the effectiveness of preventive measures and inform future strategies to reduce transmission.Keywords: hepatitis B virus, transfusion-transmitted infections, epidemiology, vaccination

Jing Su,1,&ast; Lina She,1,&ast; Yang Fan,1 Honghong Wang,2 Qiaorui Zhang,1 Jiao Zhang,1 Hongyun Ma1 1Department of Obstetrics and Gynecology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pathology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyun Ma, Department of Obstetrics and Gynecology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, No. 301, Zhengyuan North Street, Jinfeng District, Yinchuan, 750002, Ningxia, People’s Republic of China, Tel +86-15378975354, Email mahongyun2021@163.comBackground: This study retrospectively analyzed the medical records of 200 patients with endometrial hyperplasia to predict the risk of concurrent endometrial cancer.Methods: Patients were categorized into either the endometrial cancer group or the endometrial hyperplasia group based on post-hysterectomy pathology. The investigation compared general information, tumor indices, fertility history, preoperative endometrial sampling methods, comorbidities, and clinical symptoms between the groups to identify risk factors for endometrial hyperplasia complicating endometrial cancer.Results: (1) Of the 200 patients, 68 (34.0%) were diagnosed with concurrent endometrial cancer post-hysterectomy. Among these, 60 (88.24%) had endometrioid adenocarcinoma, while 8 (11.76%) had other types. Stage I was identified in 58 patients (85.29%) and Stage II in 10 patients (14.71%). High differentiation was observed in 57 cases (83.82%), moderate differentiation in 7 cases (10.29%), and poor differentiation in 4 cases (5.89%), indicating that most endometrial cancers complicated by hyperplasia were early-stage, well-differentiated endometrioid carcinomas; (2) Univariate analysis revealed statistically significant differences in age, menopausal status, length of menopause, and preoperative endometrial pathology of severe atypical hyperplasia between the groups; (3) Multivariate analysis indicated significant differences for age ≥ 53.5 years (OR: 4.307, 95% CI: 2.018– 9.192, p < 0.05), menopausal status (OR: 5.250, 95% CI: 2.449– 11.252, p < 0.05), and severe atypical endometrial hyperplasia (OR: 4.817, 95% CI: 1.260– 18.419, p < 0.05); (4) Significant differences were observed among patients with endometrial hyperplasia when stratified by the presence of zero, one, two, or three high-risk factors.Conclusion: In conclusion, patients aged ≥ 53.5 years, those who are menopausal, and those with severe atypical endometrial hyperplasia preoperatively are at higher risk for endometrial cancer. The risk increases with the number of high-risk factors present in patients with atypical endometrial hyperplasia.Keywords: retrospective, endometrial hyperplasia, endometrial cancer, clinical features, high-risk factors, regression

Qingfei Yu, Qin Zhang Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qin Zhang, Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, No. 11 Wuyingshan Middle Road, Tianqiao District, Jinan, Shandong, 250031, People’s Republic of China, Tel/Fax +8615628768081, Email jtyyzq@126.comPurpose: Pulmonary hypertension (PH) is a serious complication in hemodialysis patients, which is associated with a significantly increased risk of morbidity and mortality. The present study aims to investigate PH frequency and associated factors in patients undergoing maintenance hemodialysis.Patients and Methods: This cross-sectional study was conducted in the hemodialysis department of the Shandong Provincial Third Hospital, China, from January 2016 to December 2022. A total of 167 consecutive patients who underwent regular hemodialysis treatment for at least three months were included in the study. Patients with a systolic pulmonary artery pressure (sPAP) value > 35 mmHg at rest were considered to have PH. The relationship between PH and various demographic, laboratory, and echocardiographic parameters was evaluated.Results: A total of 93 patients (55.7%) were diagnosed with PH. Multivariate logistic regression analysis indicated that low serum levels of albumin (OR 0.89, 95% CI 0.82– 0.98, p = 0.017), low serum levels of triglycerides (OR 0.32, 95% CI 0.15– 0.69, p = 0.003), and high right atrial diameter (OR 1.19, 95% CI 1.04– 1.37, p = 0.011) were significantly associated with an increased risk of PH.Conclusion: PH is a common finding in hemodialysis patients and is independently associated with serum levels of albumin, serum levels of triglyceride, and right atrial diameter; this suggests that evaluating these non-invasive and relatively easily available parameters may be useful in identifying patients with a high risk of PH. However, further studies are required to confirm these findings.Keywords: pulmonary hypertension, triglycerides, pulmonary artery, renal dialysis, echocardiography, albumins

Jie Zhang, Xuelin Yao, Yijing Chen, Qing Feng, Yi Zhang, Tian Jiang, Songtao Tang, Nan Zhang, Fang Dai, Honglin Hu, Qiu Zhang Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qiu Zhang; Honglin Hu, Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Shushan District, 230032, People’s Republic of China, Email zhangqiu@ahmu.edu.cn; huhonglin@ahmu.edu.cnBackground: Diabetes mellitus and hypertension often coexist and share common risk factors. This study investigated the correlation between glycemic management and the prevalence of hypertension among Chinese adults diagnosed with type 2 diabetes mellitus (T2DM).Methods: This study included 1715 patients with T2DM from four cities in Anhui Province, China. Sociodemographic characteristics of the sample participants were collected via questionnaires. A univariate analysis of variance (ANOVA) was utilized for continuous variables, and chi-square testing was used for categorical variables. Binary logistic regression was utilized to examine the relationship between blood pressure and variables including fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), physical activity, dyslipidemia, and family history of hypertension.Results: FPG levels did not increase the risk of hypertension, while HbA1c was significantly and negatively associated with hypertension risk. HbA1c levels ranged from 7.2 to 8.6%, with odds ratios (OR) of 0.68 and 95% confidence intervals (CI) of 0.48 to 0.97 and a significant p value of less than 0.05. For the HbA1c levels above 8.6%, the OR was 0.58 with a 95% CI of 0.39 to 0.87 and a significant p value of less than 0.01. Furthermore, advanced age, higher BMI, greater waist circumference, presence of dyslipidemia, and positive family history of hypertension were all found to be significantly and independently linked to a heightened risk of developing hypertension. These associations remain significant after further adjustment.Conclusion: There was a negative association between HbA1c and the risk of hypertension, and the association remained significant after adjustment for antihypertensive drug use.Keywords: FPG, HbA1c, T2DM, hypertension

Feng Yao,1,&ast; Chenguang Wang,2,&ast; Jie Ding,1 Qian Zhang,1 Liang Zheng,1 Qin Zhang,1 Tianshu Yang,2 Xunmin Zhang,2 Yong Shan,2 Sheng Hou,2 Hao Wang,2 Renpeng Zhou,1 Wei Hu1 1Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Taizhou Mabtech Pharmaceutical Co., Ltd, Taizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Hu; Renpeng Zhou, Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, Anhui, 230601, People’s Republic of China, Tel/Fax + 86 0551 65997164, Email huwei@ahmu.edu.cn; zhourenpeng@ahmu.edu.cnPurpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects.Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints.Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00– 125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab.Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar.Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).Keywords: CMAB015, secukinumab, biosimilar, pharmacokinetics, safety, immunogenicity

Yucheng Wu,1,&ast; Jie Qiu,1,&ast; Xiang Sha,1,&ast; Benbingdi Gong,1 Jian Wang,1 Wei Yuan,1 Jie Lin,1 Lichun Wang,1 Qingqing Zhang2 1Department of Cardiology, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 2Panvascular Management Center, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lichun Wang, Department of Cardiology, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou, 225300, Jiangsu Province, People’s Republic of China, Email 18652711566@163.com Qingqing Zhang, Panvascular Management Center, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou, 225300, Jiangsu Province, People’s Republic of China, Email 18061986120@189.cnBackground: Management strategies for stable angina include pharmacotherapy, revascularization, and exercise-based cardiac rehabilitation (CR). The optimal treatment for stable angina patients with severe coronary artery stenosis remains unclear. This study aimed to compare interventional therapy with exercise rehabilitation in this population.Methods: Fifty stable angina patients with severe coronary stenosis who underwent stent implantation were included in the optimal medical therapy (OMT) plus percutaneous coronary intervention (PCI) group, and 50 patients who did not undergo interventional treatment were included in OMT plus CR group receiving exercise rehabilitation guidance for one year. Cardiovascular composite endpoint events, cardiopulmonary fitness, and quality of life scale scores were assessed after one year.Results: No significant difference in incidence of cardiovascular composite endpoint events was observed between OMT plus PCI group with OMT plus CR group (20.0% vs 14.6%) after one year. Cardiopulmonary fitness represented as peak VO2 (19.2± 3.5 vs 17.6± 3.2 mL/kg/min), peak load (120± 19 vs 108± 20 W), and AT (13.5± 1.5 vs 12.1± 1.3 mL/kg/min) were significantly higher in the rehabilitation group than the intervention group after one year. Both groups showed improvement in their quality of life, but the rehabilitation group improved in more scales.Conclusion: Interventional therapy did not reduce cardiovascular events compared to exercise-based rehabilitation in stable angina patients with severe coronary artery stenosis, but the rehabilitation can improve cardiovascular fitness and quality of life more.Keywords: cardiac rehabilitation, stable angina, percutaneous coronary intervention, cardiopulmonary fitness

Bo Liu,&ast; Yao Zhang,&ast; Zheng Yuan, Qiang Zhang Department of Orthopaedics, Beijing Ditan Hospital, Capital Medical University, National Center for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Zhang, Department of Orthopaedics, Beijing Ditan Hospital, Capital Medical University, National Centre for Medical Infectious Diseases, No. 8 Jingshun Eest Road, Beijing, 100015, People’s Republic of China, Email sydtzhangqiang@163.comBackground: Brucellosis is a zoonotic disease that can affect various organs, including the spine. Cervical spondylitis caused by Brucella is rare but can lead to significant morbidity if not diagnosed and treated promptly.Case Presentation: We report a case of a 46-year-old female who presented with intermittent high fever and intractable neck, shoulder, and back pain for two months. She was diagnosed with Brucella cervical spondylitis based on clinical manifestations, Rose-Bengal Plate Agglutination Test (RBPT, positive), and cervical MRI findings. She was treated with a combination of antibiotics for at least two weeks, followed by surgical intervention including abscess clearance, partial vertebral resection, and titanium mesh bone fusion. Real-time Polymerase Chain Reaction (RT-PCR) confirmed the presence of sheep Brucella DNA. The patient recovered well postoperatively with significant pain reduction and restoration of full mobility in the right upper limb.Conclusion: This case highlights the diagnostic value of RT-PCR and tissue biopsy in cervical brucellosis spondylitis. Our study found that anterior cervical subtotal corpectomy can restore cervical stability, clear abscess, and relieve spinal cord compression on the basis of drug treatment, with good clinical results.Keywords: Brucellosis, cervical spondylitis, anterior cervical subtotal corpectomy, RT-PCR, gam staining, case report

Bo Liu, Yao Zhang, Qiang Zhang Department of Orthopaedics, Beijing Ditan Hospital, Capital Medical University, Beijing, National Center for Infectious Diseases, Beijing, People’s Republic of ChinaCorrespondence: Qiang Zhang, Department of Orthopaedics, Beijing Ditan Hospital, Capital Medical University, National Center for Infectious Diseases, No. 8 Jingshun Eest Road, Beijing, 100015, People’s Republic of China, Email sydtzhangqiang@163.comBackground: Osteonecrosis is a common complication, particularly in HIV-infected patients undergoing long-term glucocorticoid therapy. This case report aims to highlight the unique “map-like” magnetic resonance imaging (MRI) changes observed in an HIV-positive patient with multiple osteonecrosis due to glucocorticoid overdose, emphasizing the importance of recognizing and managing this complication in this high-risk population.Case Presentation: A 29-year-old HIV-positive male patient developed extensive multi-joint osteonecrosis involving 7 joint sites (right shoulder, bilateral hips, bilateral knees, and bilateral ankles) after 6 months of high-dose glucocorticoid treatment for an opportunistic pneumonia associated with his HIV status. The patient required prolonged glucocorticoid therapy to manage the severe lung infection. MRI revealed characteristic “map-like” changes, with the osteonecrotic areas distributed in a linear, clustered, or map-like pattern. To alleviate his condition and improve joint function, the patient underwent a customized treatment plan, including total hip replacement for the left hip, core decompression surgery for the right hip. Following surgical intervention, the patient experienced reduced joint pain and improved joint mobility.Conclusion: This case underscores the potential risk of extensive multi-joint osteonecrosis in HIV-positive patients receiving long-term high-dose glucocorticoids, with the “map-like” MRI changes being a distinctive imaging feature. It emphasizes the importance of close monitoring and timely implementation of effective interventions in this high-risk population. Notably, core decompression surgery can improve local blood circulation, slow disease progression, and serve as an effective minimally invasive treatment option for early-stage osteonecrotic lesions.Keywords: HIV, MRI, “map-like”changes, osteonecrosis, multiple sites, case report

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Qing Zhang, Yao Xu, Hao Wang, Xuelian Pang, Qingfeng Meng Department of Cardiology, Qilu Hospital of Shandong University, Qingdao, People’s Republic of ChinaCorrespondence: Xuelian Pang; Qingfeng Meng, Email pxl18561810097@163.com; mengfeng0912@163.comAbstract: Transcatheter aortic valve replacement (TAVR) has been recently indicated for the treatment of patients with severe aortic stenosis in all risk profiles. At present, TAVR has become mature at home and abroad, but the relevant experience is deficient in the treatment of aortic valve stenosis with outflow tract stenosis. One case of a high-risk surgical patient was included in this paper who suffered from severe aortic valve stenosis with left ventricular outflow tract (LVOT) stenosis. In this case, TAVR was performed with deep implantation of a new valve and both aortic valve stenosis and LVOT stenosis were treated through a single TAVR procedure. This case highlights the vital role of such treatment in dealing with both aortic valve stenosis and LVOT stenosis through a single TAVR procedure, thus providing valuable information for similar cases.Keywords: severe aortic valve stenosis, left ventricular outflow tract, LVOT, stenosis, transcatheter aortic valve replacement, TAVR

Shaoqiu Zhang,1,&ast; Qun Zhang,2,&ast; Jian Wang,1,3,&ast; Yifan Pan,4 Zhiyi Zhang,5 Yu Geng,1 Bei Jia,1 Bing Tian,2 Yali Xiong,1 Xiaomin Yan,1 Jie Li,1,3– 5 Huali Wang,6 Rui Huang,1,3– 5 Chao Wu1,3– 5 1Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu; Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn; doctor_hr@126.comBackground: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients.Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan–Meier methods.Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001).Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients.Keywords: severe fever with thrombocytopenia syndrome, red blood cell distribution width, prognosis, survival

Yatian Jia,1,2 Qian Zhang,1– 3 Yihua Zhang,2 Hui Wang,1,2 Qingmei Niu,1,2 Ruifang Zhu,4 Jia Li,1 Wen Fan,1 Yuexing Zhang2 1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2School of Nursing, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 3School of Nursing/Research Center of Dietary Therapy Technology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Editorial Office, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Qian Zhang, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Xiaodian District, Taiyuan, Shanxi, People’s Republic of China, Email zhangqian@d.sxmu.edu.cnBackground: Hyperlipidemia has been demonstrated to be an autonomous predictor of numerous cardiovascular and cerebrovascular ailments, and research indicates that polyphenols have preventive and therapeutic effects on hyperlipidemia. Nevertheless, the impact of polyphenol-rich foods on blood lipids and oxidative stress status in patients with hyperlipidemia remains inconclusive.Objective: To examine the impact of polyphenol-rich foods on lipid levels and oxidative stress in individuals with hyperlipidemia.Methods: To retrieve papers published from the establishment of the database through October 9, 2023, eight databases were searched: the Chinese National Knowledge Infrastructure, the China Biomedical Literature Database, the Wanfang Database, the China Science and Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. The quality of include studies was assessed using the Cochrane Risk of Bias in Randomized Trials tool, v2.Results: The study involved 13 surveys encompassing 640 patients diagnosed with hyperlipidemia. The scope of the food surveys included 12 commonly consumed food groups and medicinal and food homologous substances. All 13 studies reported the effects of polyphenol-rich foods on blood lipids, with significant improvements observed in blood lipid levels for 9 types of foods. Eight studies examined the impact on oxidative stress, and six foods demonstrated a significant reduction in oxidative stress levels. The observed effects were found to be influenced by factors such as dosage, duration of intervention, and gender.Conclusion: Foods abundant in polyphenols play a crucial role in the prevention and treatment of hyperlipidemia by counteracting oxidative stress and regulating metabolic disorders. The confirmation of certain positive effects by several studies notwithstanding, discrepancies in results arise from various factors, necessitating further large-scale, prospective, well-designed randomized controlled studies to address this issue.Keywords: polyphenols, hyperlipidemia, blood lipids, oxidative stress, systematic review

Ziyu Li,1,&ast; Qiuyan Zhang,2,&ast; Yuhe Gao,3,&ast; Fang Wan,3 Yincang Wang,3 Bin Hou,2 Wenwen Cui,4,5 Yanan Wang,2 Wei Feng,2 Yunlong Hou4,5 1Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, People’s Republic of China; 2New Drug Evaluation Center, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, People’s Republic of China; 3Graduate School, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 4National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, People’s Republic of China; 5Key Laboratory of State Administration of TCM (Cardio-Cerebral VesselCollateral Disease), Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunlong Hou, Email houyunlonghrb@Hotmail.comBackground: The LuoBiTong (LBT) capsule, a novel traditional Chinese medicine formulation, is currently in Phase III clinical trials. Preliminary preclinical and Phase II clinical studies suggest its efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying mechanisms of its action remain to be elucidated.This research aims to explore the effects and mechanisms of LBT in conjunction with a maintenance dose of methotrexate (M-MTX) on RA.Methods: A Collagen-Induced Arthritis (CIA) mouse model was used to evaluate the anti-RA effects of LBT combined with M-MTX. Assessments included foot swelling, arthritis scoring, serum inflammatory factor analysis, and histopathological examination of the foot. These effects were compared with those of high-dose MTX (H-MTX). Network pharmacology was employed to construct a compound-target network for RA, based on drug composition, to predict its potential mechanism of action. Flow cytometry, Western Blot, and immunohistochemical analyses in animal models identified multiple inflammatory pathways targeted by LBT to augment the anti-RA effects of MTX.Results: The study revealed that LBT combined with M-MTX significantly alleviated CIA-induced arthritis without adverse effects. The combination of LBT and M-MTX showed similar or superior efficacy in regulating macrophage polarization, NF-κB, MAPK signaling pathways, and in the suppression of TH-17 expression in proinflammatory cells. These findings suggest that LBT may exert a multi-pathway therapeutic effect in RA treatment. The predicted pharmacological targets and mechanisms align well with this hypothesis.Conclusion: LBT, when combined with MTX, enhances the anti-RA effect by targeting multiple inflammatory pathways, demonstrating significant therapeutic potential.Keywords: rheumatoid arthritis, traditional Chinese medicine, methotrexate, network pharmacology

Qin Zhang,1 Rui Zhao,1 Yaqing Wu,2 Liming Zhang,1 Yi Feng2 1Endoscopy Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yi Feng, Department of Anesthesiology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Email doctor_yifeng@sina.comPurpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy.Patients and Methods: A total of 120 patients aged 60– 75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients’ Mini-cog score and recovery questionnaires were compared.Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P< 0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P< 0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P< 0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient’s life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05).Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.Keywords: gastrointestinal endoscopy, anesthesia, remimazolam besylate, etomidate, propofol

Qingyi Liu,1,2 Qiongdan Zhang,1,2 Zhijian Yao,1,2 Gangqiang Yi,2 Yeonseok Kang,3 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Ronggeng Fu,2 Wenbing Sheng,1,2 Lidong Cheng,4 Wei Wang,1,2 Huizhen Wang,1,2 Caiyun Peng1,5 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3College of Korean Medicine, Wonkwang University, Jeonbuk, Korea; 4Hunan Yirentang Chinese Herbal Pieces Co., Ltd, Changde, People’s Republic of China; 5Institute of Innovation and Applied Research in Chinese Medicine Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Huizhen Wang; Caiyun Peng, Tel +86-151-1648-1295 ; +86-138-7480-7689, Email whuiz0086@163.com; caiyunpeng@hnucm.edu.cnAbstract: Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018– 2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future. Keywords: EVs, TEVs, DNA walker, detection

Qiao Zhang,1,&ast; Lei Shi,1,&ast; Yanping Lin,2,&ast; Huirong Dai,1 Yixuan Bai,1 Pan You1 1Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China; 2The Third Hospital of Xiamen, Xiamen, Fujian, 361100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan You, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China, Tel/Fax +86-592-5392620, Email panyou001@yahoo.comPurpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia.Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed.Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS).Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.Keywords: biochemical characteristics, lymphocyte, mitochondrial damage, COVID-19, schizophrenia

Qianwen Zhang,1,&ast; Shengcen Zhang,1,&ast; Binbin Xu,1 Luyan Dong,1 Zhichang Zhao,2 Bin Li1 1Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fujian, 350001, People’s Republic of China; 2Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li, Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fujian, 350001, People’s Republic of China, Email leonlee307@hotmail.com Zhichang Zhao, Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email slip2046@126.comBackground: Hospital wastewater (HWW) promotes the spread of carbapenem resistance genes (CRGs). Aeromonas carry a large number of CRGs in HWW, they may play a role as a suitable reservoir for CRGs, while resistomes in HWW are still poorly characterized regarding carbapenem resistant Aeromonas. Thus, the aim of the study was to evaluate the molecular epidemiological characteristics of carbapenem resistant Aeromonas in HWW.Methods: A total of 33 carbapenem resistant Aeromonas were isolated from HWW. Antimicrobial susceptibility testing and polymerase chain reaction (PCR) were used to assess the antimicrobial resistance profiles. Molecular typing was performed using enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and multilocus sequence typing (MLST). The horizontal transmission mode of blaKPC was explored through conjugation and transformation experiments. The stability of blaKPC-IncP-6 plasmids was assessed through plasmid stability and in vitro competition test. The PCR mapping method was used to investigate the structural diversity of blaKPC.Results: The detection rates of blaKPC and cphA in Aeromonas were 97.0% and 39.4% respectively. Aeromonas caviae were grouped into 13 clusters by ERIC-PCR and 12 STs by MLST. Aeromonas veronii were grouped into 11 clusters by ERIC-PCR and 4 STs by MLST. 56.3% blaKPC were located on mobilizable IncP-6 plasmids. blaKPC-IncP-6 plasmid showed high stability and low cost fitness.Conclusion: Carbapenem resistant Aeromonas from HWW mainly carried blaKPC, which exhibited great structural diversity. Aeromonas might serve as reservoirs for blaKPC and blaKPC might spread mainly through transformation in HWW.Keywords: hospital wastewater, carbapenem resistance, Aeromonas, IncP-6, blaKPC

Bo Zhang,1,2 Minmin Guo,2 Ting Dong,2 Huajuan Yang,2 Qiujuan Zhang,2 Quanxin Yang,2 Xiaoqian Zhou,2 Cuiping Mao,2 Ming Zhang1 1Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Department of Medical Imaging, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of ChinaCorrespondence: Ming Zhang, Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email zmmri@163.comPurpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP.Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc.Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton’s Depression Scale (HAMD) scores (r = − 0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC.Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.Keywords: low back pain, nucleus accumbens, resting-state functional connectivity, dynamic causal modelling

Yidong Cui,1 Qingming Liu,2 Qiqiang Zhang,3 Xuemei Di,3 Hai Zhang3 1Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 2Department of Neurology, Shandong Second Provincial General Hospital, Jinan, 250012, People’s Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hai Zhang, Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Shanghai, 200092, People’s Republic of China, Tel/Fax +8621-20261401, Email zhxdks2005@126.comBackground: Aconitum carmichaelii (Fuzi) has been conventionally used to cure a variety of ailments, such as pain, cold sensations, and numbness of limb muscles (Bi Zheng) in China. Our prior investigations identified Benzoylaconine (BAC) as a bioactive alkaloid derived from Aconitum carmichaelii, with other studies also demonstrating its significant pharmacological potential.Purpose: This study aimed to explore the potential of BAC as a protective agent against skeletal muscle ischemia-reperfusion (I/R) injury and to elucidate the underlying mechanisms.Methods: In vivo models involved subjecting Sprague-Dawley rats to I/R through femoral artery ligation followed by reperfusion, while in vitro models utilized C2C12 cells subjected to hypoxia/reoxygenation (H/R). CCK-8 assay was used to assess cell viability. TUNEL staining and flow cytometric analysis were used to measure cell apoptosis. Biochemical assay was used to assess skeletal muscle injury and oxidative stress. Immunofluorescence and Western blot were performed to determine protein levels.Results: BAC effectively protected muscle tissue from I/R injury, enhancing cell viability (p< 0.01), elevating SOD levels (p< 0.05), and reducing CK (p< 0.01), LDH (p< 0.01), ROS (p< 0.01), MDA (p< 0.01), and apoptosis-related molecules in vivo and in vitro (p< 0.05, p< 0.01). Mechanistically, BAC increased the expression of IF1, phosphorylated AMPK, facilitated the translocation of nuclear Nrf2, and induced the expression of HO-1 (p< 0.01). Notably, AMPK inhibitor Compound C significantly hindered the ability of BAC to ameliorate H/R-induced cell injury (p< 0.05), oxidative stress(p< 0.01), and apoptosis (p< 0.05), as well as promote Nrf2 nuclear translocation (p< 0.01). Moreover, silencing of IF1 with siRNA abolished BAC-induced activation of AMPK/Nrf2 axis (p< 0.01).Conclusion: Our study provides novel evidence supporting the potential of BAC as a myocyte-protective agent against I/R injury, and we establish a previously unknown mechanism involving the activation of the IF1-dependent AMPK/Nrf2 axis in mediating the protective effects of BAC. Keywords: Benzoylaconine, ischemia-reperfusion injury, oxidative stress, AMPK, IF1

Qing Lin,1,2,&ast; Yafei Jing,2,3,&ast; Cailing Yan,2 Xinyi Chen,2 Qiong Zhang,2 Xinhua Lin,2,3 Yunlu Xu,2,4 Bing Chen2,3 1Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Pharmacy, Fujian Medical University, Fujian, People’s Republic of China; 3Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Chen, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email BingChen_001@126.com; BingChen_001@fjmu.edu.cn Yunlu Xu, Center of Translational Hematology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email xuyunlu3578@126.comBackground: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.Methods: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.Results: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78± 1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78± 5.93%).Conclusion: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.Keywords: cobra venom cytotoxin, tumor microenvironment, pH-responsive, targeted delivery, liposomes

Ying Wang,1 Han-Xin Yao,1 Zhen-Yi Liu,1 Yi-Ting Wang,1 Si-Wen Zhang,2 Yuan-Yuan Song,1 Qin Zhang,1 Hai-Di Gao,1 Jian-Cheng Xu1 1Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Endocrinology & Metabolism, First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Jian-Cheng Xu, Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China, Tel/Fax +86-043188782595, Email xjc@jlu.edu.cnObjective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University.Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936– 0.984) and 0.9326 (95% CI: 0.8747– 0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model.Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.Keywords: diabetic kidney disease, type 2 diabetes, machine learning model, random forest algorithm

Qiuyue Zhang,1– 5,&ast; Qi Zhang,6,&ast; Zhiyu Duan,2– 5,7 Pu Chen,2– 5 Jing-jing Chen,2– 5 Ming-xv Li,8 Jing-jie Zhang,9 Yan-hong Huo,10 Wu-xing Zhang,11 Chen Yang,12 Yu Zhang,12 Xiangmei Chen,2– 5 Guangyan Cai2– 5 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Key Laboratory of Kidney Diseases, Beijing, People’s Republic of China; 4National Clinical Research Center for Kidney Diseases, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Kidney Diseases Research, Beijing, People’s Republic of China; 6Department of Nephrology, Capital Medical University Electric Power Teaching Hospital, Beijing, People’s Republic of China; 7Department of Nephrology, Fourth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 8Department of Nephrology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 9Department of Nephrology, Third Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 10Department of Nephrology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 11Department of Nephrology, Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 12School of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyan Cai, Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Hospital 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Email caiguangyan@sina.comPurpose: The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort.Patients and Methods: We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan–Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Results: The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: − 0.27 to 0.34; IDI 0.003, 95% CI: − 0.009 to 0.019).Conclusion: : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.Keywords: IgAN Progression, statistical validation, risk analysis, progression risk, prediction models, older adults

Qian Zhang,1 Xiaomei Wang,1 Mingzhe Liu,1 Bin Li,1 Kun Zhang,1 Yaqi Han,1 Jiali Li,2 Yan Xin,3 Yan Huo,1 Zhenjie Hu1 1Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 2Department of Intensive Care Unit, The Sixth People’s Hospital of Hengshui, Hengshui, Hebei Province, 053000, People’s Republic of China; 3Department of Intensive Care Unit, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaCorrespondence: Yan Huo; Zhenjie Hu, Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Changan District, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095367, Email huoyan523@hebmu.edu.cn; 46400533.hebmu.edu.cnObjective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW).Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW.Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill.Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.Keywords: diaphragmatic excursion, diaphragm thickening fraction, handgrip dynamometer, ICU acquired weakness

Xin Zheng,&ast; Qiaoqing Zhang,&ast; Weijuan Su, Wei Liu, Caoxin Huang, Xiulin Shi, Xuejun Li Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Province Key Laboratory of Translational Research for Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiulin Shi; Caoxin Huang, Email shixiulin2002@163.com; cxhuang@xmu.edu.cnPurpose: Nutrient intake for pregnant women with gestational diabetes mellitus (GDM) is important to ensure satisfactory birth outcomes. This study aims to explore the dietary profiles of patients with GDM, compare the results with the Chinese dietary guidelines or Dietary Reference Intakes (DRIs) from China and investigate the relationship between maternal dietary intake and pregnancy outcomes.Patients and Methods: A total of 221 patients with GDM in the second trimester were included in the cohort. Dietary intake data were collected using a 24-hour recall method for three consecutive days. The pregnancy outcomes of these participants were subsequently monitored. Both univariate logistic regression and multivariate logistic regression analyses were conducted to explore the associations between dietary intake variables or general characteristics variables and adverse pregnancy outcomes.Results: Participants with adverse pregnancy outcomes showed a lower intake of iodine and vitamin D, a lower percentage of dietary energy intake from carbohydrates and a higher percentage of dietary energy intake from fats, compared to participants without adverse pregnancy outcomes. The gestational weight gain and family history of diabetes were associated with an increased risk of adverse pregnancy outcomes. Conversely, regular exercise, the intake of iodine and Vitamin D, and the percentage of dietary energy intake from carbohydrates were associated with a decreased risk.Conclusion: The daily diet of pregnant women with GDM in China did not meet the dietary guidelines or DRIs. The low intake of Vitamin D and iodine, the low dietary carbohydrate ratio, family history of diabetes, lack of exercise, and high gestational weight gain were associated with increased risk of adverse pregnancy outcomes in pregnant women with GDM.Keywords: gestational diabetes, nutrient intake, dietary reference intakes, pregnancy outcomes, adverse pregnancy outcome

Zhihan Zhu,1,&ast; Qiankun Zhang,1,&ast; Jia Feng,1 Sonia Zebaze Dongmo,1 Qianqian Zhang,1 Songze Huang,1 Xiaowen Liu,1 Guilong Zhang,2 Lukui Chen1 1Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lukui Chen, Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, People’s Republic of China, Email neuro_clk@hotmail.com Guilong Zhang, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email longshe05@sina.comAbstract: Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.Keywords: neural stem cells, small extracellular vesicles, ischemic stroke, neuroprotection, neural regeneration

XiaoLiang Wang,1,&ast; XiaoDong Ni,1,&ast; YanYan Wei,1 LiHua Xu,1 XiaoChen Tang,1 HaiChun Liu,2 ZiXuan Wang,3 Tao Chen,4,5 JiJun Wang,1 Qing Zhang,1 TianHong Zhang1 1Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Engineering Research Center of Intelligent Psychological Evaluation and Intervention, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 2Department of Automation, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Psychology, Shanghai Xinlianxin Psychological Counseling Center, Shanghai, People’s Republic of China; 4Big Data Research Lab, University of Waterloo, Waterloo, Ontario, Canada; 5Labor and Worklife Program, Harvard University, Cambridge, MA, USA&ast;These authors contributed equally to this workCorrespondence: TianHong Zhang; Qing Zhang, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Road, Shanghai, 200030, People’s Republic of China, Tel +86-21-34773065, Fax +86-21-64387986, Email zhang_tianhong@126.com; qing.zhang@smhc.org.cnIntroduction: Despite numerous studies investigating personality disorder (PD) and childhood maltreatment (CM) characteristics in individuals with schizophrenia (SZ), there remains a scarcity of research focusing on sex differences in PD and CM within large samples of SZ patients.Methods: A total of 592 participants (257 males, 335 females) were consecutively sampled from patients diagnosed with SZ at the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. PDs were assessed using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were evaluated using the Chinese version of the Child Trauma Questionnaire Short Form.Results: Male patients exhibited a prominent self-reported trait of antisocial PD (t=1.972, p=0.049), while female patients demonstrated a notable emphasis on histrionic PD traits (t=− 2.057, p=0.040). Structured interviews for PD diagnoses further indicated a higher comorbidity of schizotypal (χ2=4.805, p=0.028) and schizoid (χ2=6.957, p=0.008) PDs among male patients compared to female patients. Additionally, male patients reported a higher degree (t=2.957, p=0.003) and proportion (χ2=5.277, p=0.022) of experiences of physical abuse in their self-reported CM. Logistic regression analyses highlight distinct factors: higher antisocial PD traits and physical abuse are associated with male patients, while histrionic PD traits and emotional abuse are associated with female patients.Discussion: These findings underscore the importance of recognizing and addressing sex-specific manifestations of personality pathology and the nuanced impact of CM in the clinical management of individuals with SZ. The study advocates for tailored interventions that consider the distinct needs associated with sex differences in both personality traits and CM experiences among SZ patients.Keywords: personality disorder, psychosis, abuse, neglect, schizophrenia

Nan Jiang,1,&ast; Wei Jin,2,&ast; Zhenghui Fu,3,&ast; He Cao,1 Hong Zheng,3 Quqing Wang,1 Qiongting Zhang,3 Kang Ju,3 Jiwei Wang1 1Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Patriotic Public Health and Health Promotion instruction, Shanghai Municipal Center for Health Promotion, Shanghai, People’s Republic of China; 3Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China, Email jiweiwang@fudan.edu.cn Kang Ju, Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China, Email jukang2009@163.comPurpose: This study aims to explore the serial mediating effect of stigma and depression on the association between social support and medication adherence.Patients and Methods: A cross-sectional survey was undertaken in the Changning District of Shanghai using a five-part questionnaire from August to December 2023. A convenient sampling method was employed, and 35 patients with schizophrenia were invited from each of the 9 streets in Changning District to participate in the survey, resulting in a total of 305 valid questionnaires collected. The questionnaire measured social support, stigma, depression, medication adherence, and demographic characteristics. Data analysis involved descriptive statistics, independent samples t-tests, ANOVA, Pearson correlation analysis, and the bootstrap method.Results: There was a direct and significantly positive association between social support and medication adherence (β = 0.69, p < 0.001). Moreover, increased levels of stigma (β = - 0.45, p = 0.013) and depression (β = - 0.09, p = 0.017) were both associated with a decline in medication adherence. Bootstrapping analysis revealed that the association between social support and medication adherence operated indirectly through stigma (β = 0.11, 95% CI: 0.03, 0.18). Additionally, social support was indirectly associated with medication adherence through depression (β = 0.15, 95% CI: 0.04, 0.30). Further analysis indicated that social support had an indirect association with medication adherence through both stigma and depression (β = 0.04, 95% CI: 0.01, 0.07).Conclusion: Stigma and depression serially mediate the association between social support and medication adherence among patients with schizophrenia. This serial multiple mediation model underscores the importance of integrating social support interventions with psychological interventions aimed at reducing stigma and depression, thereby effectively enhancing medication adherence in patients with schizophrenia.Keywords: social support, stigma, depression, medication adherence, schizophrenia

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

Liwen Feng,1 Junbo Liang,1 Naiguo Wang,2 Qingyu Zhang2 1Department of Orthopedics, Weihaiwei People’s Hospital, Weihai, Shandong Province, 264200, People’s Republic of China; 2Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250021, People’s Republic of ChinaCorrespondence: Qingyu Zhang, Tel +86-13296402823, Email zqy2008512@163.com; zqy2008512@126.com; zhangqingyu@sdfmu.edu.cn Naiguo Wang, Tel +86-13505319917, Email naiguow@outlook.comPurpose: The purpose of this study is to preliminarily assess the change in perioperative systemic inflammatory markers and clinical outcomes between open TLIF and BE-TLIF procedures.Patients and Methods: In total, 38 patients who underwent single-level lumbar fusion surgery (L4-5 or L5-S1) were retrospectively reviewed. 19 patients were treated by the BE-TLIF technique, while the other patients were managed using open TLIF. The perioperative serum C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) of the two groups were compared to determine if there was a statistical difference. Meanwhile, clinical evaluations were conducted to assess various factors including operative duration, estimated blood loss (EBL), drainage catheter stay, length of hospitalization, visual analogue scale (VAS), and Oswestry disability index (ODI) scores.Results: The perioperative analysis revealed that BE-TLIF cases experienced a longer operative duration than open TLIF cases (open TLIF: 138.63 ± 31.59 min, BE-TLIF: 204.58 ± 49.37 min, p < 0.001). Meanwhile, the EBL showed an increased trend in the BE-TLIF group (260.7 ± 211.9 mL) in comparison with the open TLIF group (200.9 ± 211.9 mL) (p =0.485). In terms of systemic inflammatory markers, the mean postoperative CRP, NLR, LMR, and PLR were lower in the BE-TLIF group than in the open TLIF group, although these differences were not statistically significant (p > 0.05). The VAS and ODI scores in both groups were significantly improved after surgery (p < 0.05).Conclusion: There was no significant difference found between BE-TLIF and open TLIF in terms of systemic inflammatory markers, and clinical outcomes. Overall, BE-TLIF can be considered a viable choice for lumbar canal decompression and interbody fusion for less invasion. It is worth noting that BE-TLIF does have a longer operation time, indicating that there is still potential for further improvement in this technique.Keywords: transforaminal lumbar interbody fusion, unilateral biportal endoscope, systemic inflammatory markers

Xiaofeng Wang,1,2,&ast; Shuo Li,3,&ast; Da Huo,4,&ast; Zhiyuan Zhu,1,2,&ast; Wenlong Wang,1,2 Hongxia He,1,2 Qian Zhang,1,2 Jiantao Li,2,5 Xu Wang1,2 1Department of Pediatric Intensive Care Unit, National Center for Cardiovascular Disease and Fuwai Hospital, Beijing, People’s Republic of China; 2School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Infection Control, Peking University First Hospital, Beijing, People’s Republic of China; 4Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Department of Infection Control, National Center for Cardiovascular Disease and Fuwai Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xu Wang, Department of Pediatric Intensive Care Unit, National Center for Cardiovascular Disease and Fuwai Hospital, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email fwpicu@163.comPurpose: Infection prevention and control (IPC) has a significant impact on the prognosis after pediatric cardiac surgery. This study aimed to provide surveillance data on the incidence and density of various infections during the COVID-19 epidemic and explore the influence of multi-drug resistant organisms (MDRO) on in-hospital prognosis after congenital heart disease surgery.Methods: This single-center retrospective study included pediatric patients who underwent cardiac surgery between 2021 and 2022. The results of the postoperative bacterial and fungal cultures and antimicrobial stewardship were collected. The demographic characteristics (age and weight), operation-related parameters (RACHS-1 grade, duration of cardiopulmonary bypass, and aortic cross clamp), and surgical outcomes (extracorporeal membrane oxygenation, delayed sternal closure, mortality, duration of mechanical ventilation, length of intensive care unit stay and hospital stay, and hospitalization costs) of MDRO and non-MDRO patients were compared.Results: A total of 4776 patients were included. There were 101 infectious culture results after the operation, with a nosocomial infection rate of 2.1%. There were 40 MDRO specimens from 36 patients, 50 non-MDRO specimens from 30 patients, and 11 fungal specimens from 10 patients. The incidence of pneumonia was 1.5%, with a ventilator-associated pneumonia incidence density of 7.2/1000 patient-days. The incidence of sepsis was 0.4%, with a catheter-related bloodstream infection incidence density of 0.24/ 1000 patient-days. The incidence density of catheter-associated tract infection was 0.45/ 1000 patient-days. The incidence of surgical site infection was 0.06%. The culture proportion before commencing antibiotics was 93% and the antibiotic consumption intensity was 30.7 DDD/100 bed-days. The length of intensive care unit stay in MDRO infection patients increased compared with that in non-MDRO infection patients, 30 (18,52) vs 17 (7,62) days, p=0.05).Conclusion: The IPC performance of Fuwai Hospital achieved satisfactory results. MDRO infection can lead to prolonged intensive care unit stay.Plain language summary: Developed countries have advanced infection prevention and control systems and comprehensive postoperative infection monitoring data for congenital heart disease. While developing countries have initiated efforts in infection prevention and control, global attention remains substantial. This study aimed to provide comprehensive infection surveillance data and identify possible implementation for further improvement in the National Center for Cardiovascular Diseases in China (Fuwai Hospital).This was a retrospective single-center study. We included pediatric patients who underwent cardiac surgery at a pediatric surgical center between 2021 and 2022, with an age limit of 14 years. Exclusion criteria included patients undergoing medical therapy, interventional therapy, or surgical therapy in other centers in Fuwai Hospital.This study, for the first time, reports the incidence of comprehensive healthcare-associated infection surveillance and targeted surveillance (encompassing device-associated infection, surgical site infection, and multi-drug resistant organisms) after pediatric cardiac surgery at the National Center for Cardiovascular Diseases in China. In addition, we report the data on antimicrobial stewardship. We compared the surgical outcome and hospitalization costs between patients with multi-drug resistant organism infection and those without multi-drug resistant organism infection and found that multi-drug resistant organism infection can lead to prolonged intensive care unit length of stay.The Fuwai Hospital achieved satisfactory infection prevention and control results. However, because China is a large developing country exhibiting notable variations in medical conditions across its diverse regions, prospective, multicenter, observational studies should be carried out for future research based on existing evidence.Keywords: nosocomial infections, pediatric cardiac surgery, multidrug-resistant organism, surgical outcomes

Qiankun Zhang,* Songze Huang,* Xiaowen Liu, Wei Wang, Zhihan Zhu, Lukui Chen Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lukui Chen, Department of Neurosurgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Email neuro_clk@hotmail.comAbstract: Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions. Additionally, the review delves into recent developments in the use of liposomes in ischemic stroke models, offering a comparative evaluation with other nanocarriers like exosomes and nano-micelles, thereby facilitating their clinical advancement. Keywords: liposome, BBB, ischemic stroke, drug carrier, liposome-based engineering