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Jiahua Cheng,1,* Wujuan Li,1,* Lanlin Wang,1,* Yu Gao,1 Yueran Ma,1 Min Zhou,1 Tian Yang,1 Changwu Yue,1,2 Long Yan,3 Yuhong Lyu1,2 1Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 2Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 3Medical Imaging Center, Yan’an Traditional Chinese Medicine Hospital, Yan’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Long Yan; Yuhong Lyu, Email yanlong840212@163.com; yuhonglyu@126.comPurpose: To explore the protective effects and mechanisms of Jiawei Qifuyin on APP/PS1 mice, a model for Alzheimer’s disease (AD).Methods: Network pharmacology tools were used to predict anti-AD targets and signaling pathways affected by Jiawei Qifuyin. In vitro studies assessed antioxidant and oxygen radical scavenging abilities, immune cell proliferation, and inflammatory cytokine levels in lipopolysaccharide-induced BV2 microglial cells. Cognitive ability in APP/PS1 mice was evaluated using the Morris Water Maze test. mRNA expression of neuroinflammatory factors, changes in intestinal microbiota, and short-chain fatty acid content were analyzed post-treatment.Results: Network pharmacology predicted that Jiawei Qifuyin affects AKT1, TNF-α, and AGE/RAGE pathways. It showed concentration-dependent antioxidant effects and modulated immune cell proliferation. IL-2, IL-6, and TNF-α levels in LPS-induced BV2 cells were significantly reduced. Treated animals exhibited improved cognitive performance, decreased brain amyloid-beta levels, and downregulated expression of IL-1β, IL-6, RAGE, and NF-κB. Significant changes in intestinal microbiota composition and SCFA content were observed.Conclusion: Jiawei Qifuyin may enhance immunity and improve cognitive impairment in APP/PS1 mice through regulation of inflammatory factors, gut microbiota, and the gut-brain axis.Keywords: Alzheimer’s disease, Jiawei Qifuyin, neuroinflammation, intestinal microbiota, short chain fatty acid

Jun Zhou,1,2,&ast; Liu Shi,1,2,&ast; Chuwei Tian,1,2 Yucheng Gao,1,2 Jinyu Wang,2,3 Jin Mao,2,4 Yan Li,2,4 Wenbin Fan,1,2 Xiangxu Chen,1,2 Cheng Zhang,1,2 Tian Xie,1,2 Yunfeng Rui1,2,&ast; 1Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Multidisciplinary Team for Geriatric Hip Fracture Comprehensive Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Rehabilitation, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Emergency, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Rui, Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86 13705182577, Email ruiyunfeng@126.comIntroduction: This study aims to assess the impacts of the Fast Access to Surgery in Emergency (FASE) strategy on (1) the workflow of multidisciplinary team (MDT) during hospitalization; (2) the clinical outcomes of geriatric femoral neck fracture (FNF) patients.Methods: A retrospective study was conducted in a single trauma center to evaluate the clinical data of geriatric FNF patients admitted through emergency from July 2017 to June 2022. The FASE strategy was implemented since Jan 1st 2020, and patients were categorized into the FASE group or the control group according to the time of admission (before/after the initiation timepoint of FASE strategy). Propensity score matching (PSM) was utilized to limit confounding bias between the two groups.Results: Finally, 344 patients were included after a one-to-one matching. The FASE strategy resulted in a slightly prolonged duration in emergency (6.02± 5.99 h vs 2.72± 4.22 h, p< 0.001) but was meanwhile associated with significant decreases in time to surgery (61.16± 38.74 h vs 92.02± 82.80 h, p< 0.001), actual surgery delay (67.18± 39.04 h vs. 94.25± 84.41 h, p< 0.001) and total length of hospital stay (10.57± 4.93 h vs 12.50± 4.73 h, p < 0.001). Besides, despite the consistency of transfusion rate between the two groups, improved blood management was achieved in the FASE group, as evidenced by a smaller drop in hemoglobin levels (− 20.49± 17.02 g/L vs − 25.28± 16.33 g/L, p = 0.013) in patients without preoperative or intraoperative transfusion. However, no significant differences were observed regarding the overall clinical outcomes such as mortality or postoperative complications.Conclusion: The Fast Access to Surgery in Emergency (FASE) for geriatric FNF patients effectively optimized the preoperative evaluation workflow, which significantly shortened time to surgery and length of hospital stay, and reduced perioperative blood loss. FASE strategy improved the surgical workflows and turnover efficiency of geriatric FNF patients, therefore could play an important role in the optimal MDT co-management for geriatric FNF patients. Keywords: femoral neck fracture, geriatric, emergency optimization, multidisciplinary management, early surgery

Jiyang Li,1,&ast; Xinxing Fei,2,&ast; Shiqi Wang,3,4,&ast; Zhangyu Xu,5,6 Fangyuan Xu,5,6 Jianxiong Wang,5,6 Yaqian Gao,7 Yue Hu5,6 1Department of Rehabilitation Medicine, Sichuan Tianfu New Area People’s Hospital, Chengdu, People’s Republic of China; 2Department of Psychiatry, Chengdu Eighth People’s Hospital (Geriatric Hospital of Chengdu Medical College), Chengdu, People’s Republic of China; 3Department of Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu, Sichuan, People’s Republic of China; 5Department of Rehabilitation Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 6Rehabilitation Medicine and Engineering Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 7Department of Rehabilitation Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaqian Gao; Yue Hu, Email 673509366@qq.com; huyue@swmu.edu.cnBackground: Many studies have been conducted on the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression. However, the overall trends in research publications in this field remain elusive. There is still little quantitative analysis of the literature in this field. Therefore, we conducted a bibliometric analysis to explore the research patterns surrounding SSRIs for depression, aiming to gain a deeper understanding of their development and impact.Methods: Publications about the use of SSRIs for the treatment of depression were identified in the Web of Science Core Collection. Visualization analysis was performed with Bibliometrix, VOSviewer, and CiteSpace.Results: A total of 1149 publications published from 1990 to 2024 were included in the bibliometric analysis. Since 1990, the annual number of published papers has increased annually, reaching the maximum value of output in 2004. Fitted curve showed that after 2004, the number of publications per year was essentially stable The United States dominates the field. Among these institutions, University of Pittsburgh excels in this field. Fava M has the highest scientific productivity and extensive academic influence. European Neuropsychopharmacology is the most active journal in this field. The three most relevant keywords were “fluoxetine”, “double-blind”, and “major depression”. The trend topics in recent years were “connectivity”, “c-reactive protein”, and “anhedonia”.Conclusion: Research on the use of SSRIs for the treatment of depression continues to receive increased attention but still requiraes further exploration and innovation. We further analyze the current research hotspots and frontiers in this field.Keywords: selective serotonin reuptake inhibitors, depression, bibliometrics, double-blind, fluoxetine, major depression

Linqiong Liu,1– 3,&ast; Pengfei Huang,1,2,&ast; Changsong Wang,1,2,&ast; Yuxi Liu,1– 3 Yan Gao,3 Kaijiang Yu1,2 1Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Heilongjiang Provincial Key Laboratory of Critical Care Medicine, Harbin Medical University, Harbin, People’s Republic of China; 3Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gao, Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email icugaoyan@163.com Kaijiang Yu, Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email drkaijiang@163.comPurpose: We aimed to identify the association between heart failure (HF) with sepsis and its mortality through Mendelian randomization (MR) and observational studies.Patients and Methods: In MR study, we utilized public summary statistics from genome-wide association studies (GWAS). We conducted univariable, multivariable and network MR analyses to investigate causal relationships between HF and sepsis, and mediating roles of cytokines and growth factors. We performed an observational analysis using the MIMIC-IV database. Propensity score matching (PSM) and logistic regression models were employed to explore causal relationships between HF and sepsis, besides short-, medium-, and long-term mortality associated with sepsis.Results: In univariable MR analysis, there was a causal relationship between genetically predicted HF (OR = 1.15, 95% CI = 1.02– 1.29, P = 0.025) and sepsis. In multivariable and network MR analyses, βNGF was independently associated with sepsis. And it mediated 17.6% (95% CI 2.45– 30.72%) of HF effect on sepsis. In the real-world observational study, acute on chronic diastolic (congestive) heart failure (DCHF) (OR = 1.59, 95% CI = 1.31– 1.93, P < 0.001), acute DCHF (OR = 2.52, 95% CI = 1.61– 3.95, P = 0.010), and acute diastolic heart failure (DHF) (OR = 1.52, 95% CI = 1.06– 2.19, P = 0.024) after PSM were associated with occurrence of sepsis. Chronic systolic (congestive) heart failure (SCHF) was associated with increased 28-day (OR = 1.75, 95% CI = 1.06– 2.91, P = 0.030), 1-year (OR = 1.80, 95% CI = 1.08– 3.00, P = 0.023), and 2-year (OR = 1.86, 95% CI = 1.12– 3.10, P = 0.018) mortality in sepsis.Conclusion: Observational and MR analyses showed a causal relationship between HF and sepsis. Chronic SCHF was related to increased short/long-term mortality in sepsis. Our study indicated βNGF a key factor in HF-induced sepsis.Keywords: βNGF, MIMIC-IV, PSM, GWAS

Yaning Gao, Liang Chen, Zhengjun Wen, Huiying Jiang, Jing Feng Respiratory and Critical Care Medicine Department, Beijing Jingmei Group General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Liang Chen, Email huxike000111@sohu.comPurpose: Our aim was to determine the risk factors for multidrug resistance in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The information of 196 patients with Klebsiella pneumoniae infection was collected. The patients were subsequently assigned to the carbapenem-resistant, multidrug-resistant, and non-multidrug-resistant groups. The risk factors for multidrug resistance in CRKP patients were assessed via least absolute shrinkage and selection operator and logistic regression analyses. Moreover, a nomogram was constructed dependent on the identified risk factors, and calibration and decision curves were plotted to detect its accuracy.Results: Length of stay (LOS) [odds ratio (OR) and 95% confidence interval (CI): 4.558 (1.157– 17.961), P = 0.030], intensive care unit (ICU) stay within 30 days [OR and 95% CI: 12.643 (3.780– 42.293), P < 0.001], Glasgow Coma Scale (GCS) score [OR and 95% CI: 13.569 (2.738– 67.236), P = 0.001], fungal infection [OR and 95% CI: 6.398 (1.969– 20.785), P = 0.002], and cardiovascular disease (CVD) [OR and 95% CI: 3.871 (1.293– 11.592), P = 0.016] were identified as risk factors for multidrug resistance in CRKP patients. The concordance index (C-index) of the constructed nomogram was 0.950 (95% CI: 0.945– 0.955). Moreover, decision curve analysis elucidated the nomogram utilization across a wide range of probability thresholds, ranging from 1% to 100%. Finally, internal validation using random data validated the robustness of the predictive model, yielding a C-index of 0.937.Conclusion: The LOS, ICU stay within 30 days, GCS score, fungal infection, and CVD were recognized as risk factors for multidrug resistance in CRKP patients. The constructed nomogram could accurately predict multidrug-resistant CRKP infections in patients.Plain Language Summary: The LOS, ICU stay within 30 days, GCS, fungal infection, and CVD were identified as risk factors for multidrug resistance in CRKP patients.The nomogram constructed in this study had high predictive accuracy.This study provides a reference for the formulation of personalized prevention and therapy strategies.Keywords: Klebsiella pneumoniae, multidrug resistance, carbapenem, prediction model, risk factors

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

Chenhao Suo,1,&ast; Yiru Gao,2,&ast; Sheng Yang,2 Wanli Zhang,2 Chao Li,3 Lanjing Ma,2 Yingchun Xu,4,5 Jianjun Lei,1 Chen Ding,2 Hailong Li,6 He Zhang,1 Tianshu Sun4,7 1Laboratory Animal Department, Northern Theater General Hospital, Shenyang, Liaoning, 110000, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, Liaoning, 110000, People’s Republic of China; 3Department of Emergency Medicine, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, 100730, People’s Republic of China; 5Medical Research Centre, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 6Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; 7Clinical Biobank, Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianshu Sun; He Zhang, Email sun_tianshu@163.com; alwayszhh@163.comIntroduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.Keywords: endocytosis, Sla1, cell wall integrity, drug susceptibility, fungal pathogenicity

Zhiyuan Yu,1– 3,&ast; Haopeng Liu,4,&ast; Rui Li,1– 3,&ast; Liai Hu,3 Chun Xiao,5 Yunhe Gao,2 Peiyu Li,1– 3 Wenquan Liang,2 Sixin Zhou,2 Xudong Zhao2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Department of Hepatobiliary Surgery, Zhangqiu District People’s Hospital, Jinan, Shandong Province, People’s Republic of China; 5Department of General Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Zhao; Sixin Zhou, Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, People’s Republic of China, Email 601489554@qq.com; 35060555@qq.comBackground: The research on lymph node metastasis (LNM) in locally advanced gastric cancer (LAGC) infiltrating the subserous tissue and serous membrane (T3-4a) is significantly inadequate. This study aims to explore the clinicopathological factors related to LNM in stages T3 and T4a LAGC, while also developing predictive nomograms.Methods: After systematic searching and rigorous screening, 1995 T3 and 1244 T4a LAGC cases who underwent surgery without neoadjuvant or perioperative chemotherapy were selected. The risk factors associated with LNM were identified using both univariate and multivariate logistic regression analyses. Subsequently, the independent variables identified through the multivariate analyses were utilized to construct a nomogram.Results: The incidence of LNM in T3 and T4a LAGC was 77.1% (1539/1995) and 83.8% (1043/1244), respectively. The following factors were found to be independently associated with LNM in T3 LAGC: preoperative serum albumin < 41g/L (P=0.007), gastrointestinal obstruction (P< 0.001), tumor location (P=0.040), tumor size > 4cm (P=0.002), mixed (P=0.001) and undifferentiated histological types (P=0.002), presence of lymphovascular invasion (LVI) (P< 0.001) and nerve invasion (P< 0.001). Additionally, in T4a LAGC cases, serum albumin < 39g/L (P=0.004), tumor size > 6cm (P=0.020), mixed (P< 0.001) and undifferentiated histological types (P< 0.001), presence of gastrointestinal hemorrhage (P=0.016), neuroendocrine differentiation (P=0.024), and LVI (P< 0.001) independently influenced the occurrence of LNM.Conclusion: This study identified the risk factors associated with LNM in T3-4a LAGC cases and constructed nomograms, thereby providing valuable guidance for formulating and implementing a multidisciplinary perioperative treatment program.Keywords: locally advanced gastric cancer, lymph node metastasis, clinicopathological factors, nomogram

Yanping Wu,1 Yueqin Zheng,1 Sumei Sha,1 Yu Wang,2 Junyan Wang,3 Wei Zhang,4 Yixuan Lu,1 Yan Cheng,1 Jie Wu,5 Bin Qin,1 Yuan Gao6 1Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Gastroenterology, Xi’an Central Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Gastroenterology, the Second Affiliated Hospital of Xi ‘an Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 4Department of General Internal Medicine, Staff Hospital of Changqing Oilfield, Xi’an, Shaanxi Province, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 6Department of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi Province, People’s Republic of ChinaCorrespondence: Bin Qin, Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi Province, 710004, People’s Republic of China, Email qinbin@xjtu.edu.cn Yuan Gao, Department of Gastroenterology, Ankang Central Hospital, Ankang City, Shaanxi Province, 725000, People’s Republic of China, Email gaoyuan015@163.comPurpose: Ischemic colitis appears to be a rare but serious complication of COVID-19. About 33.3% hospitalized COVID-19 patients who underwent endoscopy showed features resembling ischemic colitis. The aim of this prospective study was to describe the symptoms, treatment, and outcomes of these patients, particularly their colonoscopy and histologic findings.Patients and methods: We conducted a prospective study on ischemic bowel disease associated with COVID-19 across four centers from December 2022 to January 2023. All cases were identified through a comprehensive search of electronic medical records for procedure-related data. The initial diagnosis of ischemic bowel disease was confirmed using colonoscopy and biopsy findings. After the patients were discharged, a 12-month follow-up was conducted through regular phone interviews to assess their clinical outcomes.Results: Overall, the study included 3 male patients and 9 female patients (age range, 33– 76 years). Abdominal pain and hematochezia always occurred within 2 weeks after COVID-19 infection (average 5.5 days). Gastrointestinal manifestations did not parallel the severity of COVID-19 infection. The descending colon was the most susceptible segment, which was involved in 10 patients (83.33%). Colonoscopy revealed diffuse redness, edema, bleeding, erosion, and ulceration of the intestinal mucosa, similar to the findings of ischemic colitis, and biopsy revealed crypt atrophy, reduction, and interstitial bleeding. All patients were self-limited without converting to chronic changes in the next 12 months.Conclusion: SARS-CoV-2 infection may induce transient acute colon ischemia within 2 weeks, accompanied by severe clinical symptoms such as acute abdominal pain and hematochezia, which are self-limiting and do not lead to chronic symptoms.Keywords: SARS-CoV-2, lower gastrointestinal bleeding, ischemic colitis, colonoscopy

Enmin Xie,1,2 Yaxin Wu,3 Zixiang Ye,1,4 Yanxiang Gao,1 Jingang Zheng1,2 1Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Cardiology, Henan Provincial People’s Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, People’s Republic of China; 4Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of ChinaCorrespondence: Jingang Zheng, Department of Cardiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing, 100029, People’s Republic of China, Email mdjingangzheng@yeah.netObjective: As a biomarker of inflammation and a core component in the coagulation pathway, fibrinogen contributes to atherosclerosis and subsequent adverse cardiovascular events and is modified by the occurrence of diabetes mellitus. However, the association between fibrinogen, diabetes status, and mortality in patients with end-stage renal disease (ESRD) and acute coronary syndrome (ACS) remains scarce.Methods: A multi-center cohort study enrolled 1079 patients with ESRD and ACS between January 2015 and June 2021. Patients were classified into three groups based on fibrinogen tertiles and were further categorized by diabetes status. The primary outcome was all-cause mortality, while the secondary outcome was cardiovascular mortality.Results: During a median 21.5 months of follow-up, 386 cases of all-cause mortality were recorded, including 262 cases of cardiovascular mortality. Multivariable Cox regression model revealed that patients with the third tertile of fibrinogen and those with diabetes experienced a significantly increased risk of all-cause mortality (fibrinogen: hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.32– 2.19; diabetes: HR, 1.36; 95% CI, 1.10– 1.68). When patients were stratified by both fibrinogen levels and diabetes status, patients in the third fibrinogen tertile with diabetes had the highest risk of all-cause mortality (HR 2.43, 95% CI 1.69– 3.48) compared to those in the first fibrinogen tertile without diabetes. Similar associations were observed for cardiovascular mortality. Notably, incorporating the combined fibrinogen and diabetes status into the Global Registry of Acute Coronary Events (GRACE) score or baseline risk model led to significant improvements in the C-statistics for predicting mortality, surpassing the advancements achieved with any single biomarker.Conclusion: In patients with ESRD and ACS, elevated fibrinogen and diabetes were associated with an increased risk of all-cause and cardiovascular mortality. Categorizing patients based on fibrinogen levels and diabetes status could provide valuable information for risk stratification of these patients.Keywords: Acute coronary syndrome, Diabetes mellitus, End-stage renal disease, Fibrinogen, Prognosis

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

Haiping Li,1,&ast; Xuesong Wang,1,&ast; Yu Wang,1 Yuanbo Gao,1 Xiaojun Zheng,1 Xifen Zhang,1 Xuxin Li,1 Xihui Zheng,1 Xisheng Fan,1,2 Guang Zuo,1 Yanfen She1,2 1College of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang City, Hebei Province, People’s Republic of China; 2Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang City, Hebei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang Zuo; Yanfen She, Hebei University of Chinese Medicine, No. 3 Xingyuan Road, Shijiazhuang City, Hebei Province, 050200, People’s Republic of China, Email zg912920315@sina.com; sheyanfen@163.comBackground: Acupuncture and related therapies are effective and safe ways to relieve the pain, and improve the health and quality of life in women with endometriosis-related pain. However, it is still unclear which treatment is the most effective. Our study aims to summarize the evidence and determine the most effective and safe method to treat the endometriosis.Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of science, China Biology Medicine, China National Knowledge Infrastructure, Wan fang Data, Chinese Scientific Journal Database and conducted manual searches of relevant papers, summarized randomized clinical trials of acupuncture-related therapies for endometriosis from database inception to 21 April 2024. After independent literature screening and data extraction that pain VAS was selected as the primary outcome measure. The quality evaluation was conducted by Review Manager 5.4. Perform network meta-analysis (NMA) used Stata 15.0 software.Results: Forty-two eligible trials involving six acupuncture-related interventions and 3,635 participants were included in this NMA. Pairwise meta-analyses show that combination therapy was more efficacious than western medicine and Chinese herb medicine for pain VAS scores, serum CA125 level and response rate results. The NMA estimates indicated that: for pain VAS scores, acupuncture (SMD: − 2.33; 95% CI: − 4.37, − 0.29) and combination therapy (SMD: 1.79 95% CI: 1.21, 2.41) were superior to western medicine. For serum CA125 level, acupoint application (SMD: − 11.33 95% CI: − 20.28, − 2.97) and combination therapy (SMD: 6.20; 95% CI: 1.60, 10.75) were associated with better efficacy when considered alongside western medicine. For response rate, combination therapy (SMD: 0.20; 95% CI: 0.14, 0.29) and auricular therapy (SMD: 8.01; 95% CI: 2.08, 45.37) were more efficacious than western medicine. The comprehensive ranking results show that acupoint catgut embedding was the best performing at lowering pain VAS scores, acupoint application was identified as the most effective in reducing serum CA125 level, and auricular therapy was ranked first in improving the response rate.Conclusion: Acupoint catgut embedding, auricular therapy, acupoint application and combination therapy may be the best solutions for the treatment of endometriosis. Additional trials are needed to develop higher-quality evidence and optimal regimens.Keywords: acupuncture, endometriosis, randomized controlled trials, network meta-analysis

Haojun Ma,1– 3,&ast; Rui Chen,1,&ast; Nannan Han,1– 3 Hanming Ge,1 Shilin Li,1 Yanfei Wang,1 Xudong Yan,1,3 Chengxue Du,1,3 Yanjun Gao,4 Gejuan Zhang,1– 3 Mingze Chang1– 3 1Department of Neurology, The Affiliated Hospital of Northwest University, Xi’an No.3 hospital, Xi’an, People’s Republic of China; 2Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, The Affiliated Hospital of Northwest University, Xi’an No.3 hospital, Xi’an, People’s Republic of China; 3Neurological Intensive Care Unit, The Affiliated Hospital of Northwest University, Xi’an No.3 hospital, Xi’an, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Northwest University, Xi’an No.3 hospital, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingze Chang, Department of Neurology, The Affiliated Hospital of Northwest University, Xi’an No.3 hospital, Xi’an, 710069, People’s Republic of China, Email changmingze191@163.comBackground: Stroke, particularly due to large vessel occlusion (LVO), is a major cause of mortality and disability globally. Endovascular therapy (ET) significantly improves outcomes for acute ischemic stroke (AIS) patients, but complications such as stroke-associated pneumonia (SAP) increase mortality and healthcare costs. This study investigates the association between blood-brain barrier (BBB) disruption and the increased risk of SAP and explores the relationship between BBB disruption and medium-term functional outcomes.Methods: The retrospective cohort study was performed on AIS patients enrolled between January 2019 to February 2023 who underwent ET. Patients were divided into two groups: BBB disruption and without BBB disruption. Multiple logistic regression model was conducted to measure the association between BBB disruption and SAP. Mediation analysis was used to estimate the potential mediation effects on the associations of BBB disruption with SAP. A restricted cubic spline (RCS) regression model was used to further outline the connection between the highest CT value of hyperattenuated lesions areas and the risk of SAP.Results: The study included 254 patients who underwent endovascular therapy, with 155 patients in the BBB disruption group (exposure) and 99 patients in the without BBB disruption group (control). Multiple logistic regression analysis revealed a significantly increased risk of SAP in patients with BBB disruption (OR = 2.337, 95% CI: 1.118– 4.990, p = 0.025). Furthermore, mediation analysis suggested that this association may be partly due to malignant cerebral oedema and haemorrhagic transformation. The study found an inverse L-shaped dose-response relationship between the maximum CT values of BBB disruption areas and the incidence of SAP. SAP partially mediated the association between BBB disruption and 3-month poor functional outcome.Conclusion: BBB disruption are a potential risk factor for SAP. BBB disruption may affect short- and medium-term prognosis of patients after ET in part through SAP.Keywords: acute stroke, stroke-associated pneumonia, hyperattenuated lesions, endovascular therapy, blood-brain barrier disruption

Jinjin Xu,1– 3,&ast; Yan Yang,1– 3,&ast; Guixue Guan,1– 3,&ast; Yuan Gao,1– 3 Qian Sun,1– 3 Guangwei Yuan,4 Xiaozuo Zhang,1– 3 Jingyun Yang,5,6 Wen Yang,1– 3 Zuobin Zhu,7 Conghui Han8,9 1Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 22206, People’s Republic of China; 3Medical University, Lianyungang, Jiangsu, China & Department of Gynecology, Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 4College of Professional Studies, Northeastern University, Boston, MA, USA; 5Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA; 6Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; 7Department of Genetics, Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 8Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Yang, Department of Gynecology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Zhenhua Road, Lianyungang, Jiangsu, 222061, People’s Republic of China, Tel +86-18961325910, Email wen_yang0@163.com Conghui Han, Department of Urology, Xuzhou Clinical School of Xuzhou Medical University, 199 Jiefang South Road, Xuzhou, Jiangsu, 221000, People’s Republic of China, Tel +86-13813461893, Email hanchdoctor@st.btbu.edu.cnObjective: This study investigates the thromboelastography (TEG) changes in patients with unexplained recurrent spontaneous abortion (URSA) to identify effective diagnostic markers for URSA.Methods: We retrospectively analyzed 160 URSA patients from the Gynecology Department of the First People’s Hospital of Lianyungang (June 2017 - June 2020) and compared them with 190 healthy, fertile women without adverse pregnancy histories (control group). TEG parameters were assessed using logistic regression, applying stepwise selection for model optimization. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, determining sensitivity and specificity. The Youden index identified optimal cut points for predictive probabilities.Results: Significant differences were observed between the URSA and control groups in coagulation reaction time (R), clot formation time (K), clot formation rate (Angle-α), and maximum clot strength (MA) (P< 0.05). Multivariable logistic regression identified R, Angle-α, and MA as independent URSA risk factors. The model demonstrated excellent discrimination (AUC: 0.940; 95% CI: 0.918– 0.962). The optimal cut point of predictive probability (Youden index) was P=0.355, yielding a sensitivity of 0.925 and specificity of 0.795.Conclusion: URSA patients exhibit a hypercoagulable state even when not pregnant. More research is needed to validate our findings and explore the potential clinical implications of anticoagulants in treating URSA.Keywords: unexplained recurrent spontaneous abortion, thromboelastography, prothrombotic state, coagulation function

Suwen Huang,1,&ast; Wei Xie,1,2,&ast; Yufan Gao,1,3,&ast; Yining Jin,1,3 Yilin Chen,1,2 Guoliang Zhou,1,2 Feng Chen,1,2 Qiaoqiao Jin,1,2 Zihao Wu,1,2 Lingsheng Wang,1,2 Chao Chen,4 Yiyun Weng,1 Guangyong Chen5 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Nutriology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 5Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyong Chen, Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email gychen@wmu.edu.cn Yiyun Weng, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email wengyiyun2012@126.comBackground and Purpose: The dynamic systemic inflammation level and stroke-associated infection (SAI) are related to the prognosis of acute ischemic stroke (AIS). We aimed to explore whether the systemic inflammatory response index (SIRI), systemic immune inflammation index (SII), and their dynamic changes possess predictability for SAI and long-term prognosis.Methods: A total of 1804 AIS patients without intravenous thrombolysis in two hospitals were included. We explored the relationship between SIRI, SII, and their dynamic changes and outcomes by constructing clusters. The mediating effects of SAI between prognosis and systemic inflammation were further evaluated.Results: Each SD increase in the concentration of SIRI exhibited a significant correlation with the risk of poor functional outcome, mortality, and functional dependency. Through K-means clustering analysis, patients with dramatically elevated or decreased systemic inflammation levels of SIRI (OR: 2.293, 95% CI: 1.279– 4.109) and SII (OR: 3.165, 95% CI: 1.627– 6.156) within 7 days had a higher risk of functional outcome. Through mediation analysis, SAI mediated the association between systemic inflammation and poor prognosis (SIRI: 33.73%, SII: 16.01%).Conclusion: Dramatically changing dynamics of SIRI and SII were significantly associated with a higher risk of poor prognosis in AIS patients. SAI mediated the association between systemic inflammation and prognosis at 1 year.Keywords: AIS, inflammation, SAI, mediation analysis, clustering analysis

Yule Wang,1 Yiran Li,2 Yue Zhou,2 Yue Gao,1 Lu Zhao2 1Zhejiang Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Senile Chronic Diseases, Department of Geriatrics, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, People’s Republic of China; 2Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Lu Zhao; Yue Gao, Email lzhao@zju.edu.cn; gaoyue@hospital.westlake.edu.cnBackground: Currently, ischemic stroke (IS) continues to significantly contribute to functional deterioration and reduced life quality. Regrettably, the choice of neuro-rehabilitation interventions to enhance post-IS outcomes is limited. Guanxinning tablet (GXNT), a multi-component medicine composed of Danshen and Chuanxiong, has demonstrated neuroprotective potential against ischemic brain injury and diabetic encephalopathy. However, the therapeutic impact of GXNT on post-IS functional outcomes and pathological injury, as well as the underlying molecular mechanisms and anti-IS active substances, remain unclear.Methods: To answer the above questions, neurological and behavioral assessment, cerebral lesions, and blood-brain barrier (BBB) integrity were combined to comprehensively investigate GXNT’s pharmacodynamic effects against post-IS injury. The possible molecular mechanisms were revealed through transcriptome sequencing coupled with experimental verification. Furthermore, the brain tissue distribution of main components in GXNT, behavioral changes of IS zebrafish, and molecular docking were integrated to identify the anti-IS active compounds.Results: Treatment with GXNT significantly mitigated the functional deficits, cerebral cortex lesions, and BBB disruption following IS. Transcriptome sequencing and bioinformatics analysis suggested that complement and coagulation cascades as well as inflammation might play crucial roles in the GXNT’s therapeutic effects. Molecular biology experiments indicated that GXNT administration effectively normalized the abnormal expression of mRNA and protein levels of key targets related to complement and coagulation cascades (eg C3 and F7) and inflammation (eg MMP3 and MMP9) in the impaired cortical samples of IS mice. The locomotor promotion in IS zebrafish as well as favorable affinity with key proteins (C3, F7, and MMP9) highlighted anti-IS activities of brain-permeating constituents (senkyunolide I and protocatechuic acid) of GXNT.Conclusion: Taken together, these intriguing findings indicate that GXNT intervention exerts a beneficial effect against post-IS injury via regulating the complement and coagulation cascades pathway and mobilizing inflammatory network. Senkyunolide I and protocatechuic acid show promise as anti-IS active compounds. Keywords: Guanxinning tablet, post-ischemic stroke injury, complement and coagulation cascades, inflammatory network mobilization, active substance

Xiaowu Wang,1,2 Tuantuan Li,1,2 Yan Liu,1,2 Yilang Zhu,1,2 Lichang Chen,1,2 Yong Gao1,2 1Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang, Anhui, People’s Republic of China; 2Department of Clinical Laboratory, Fuyang Infection Disease Clinical College of Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Yong Gao, The Second People’s Hospital of Fuyang City, No. 1088, West Yinghe Road, Fuyang, Anhui, People’s Republic of China, Email fyeryuangy8@126.comObjective: We retrospectively review consecutive patients with nontuberculous mycobacterium (NTM) pulmonary disease reported from a designated hospital for infectious diseases in the Fuyang district of China to determine the clinical characteristics of these patients.Methods: This research enrolled 234 patients with NTM pulmonary disease between January 2018 and May 2023 in the Fuyang district of China. Data were collected from the electronic medical records. The NTM strain composition and clinical characteristics of NTM pulmonary disease were retrospectively analyzed.Results: 73 (31.20%) patients had previous tuberculosis (TB) or TB exposure history and bronchiectasis. Mixed NTM infection accounted for 12.39%. Mycobacterium intracellulare strain was detected in 132 patients (49.62%). Women were found to be more affected by Mycobacterium avium infection, and men by Mycobacterium abscessus infection. Mycobacterium avium (34.21%) and Mycobacterium abscessus (33.33%) strains were most common in people with previous TB or TB exposure history. Among respiratory tract-related diseases, patients with bronchiectasis had the highest isolation rate of Mycobacterium avium (55.36%). Women were susceptible to bronchiectasis (P < 0.01). The median of mononuclear-to-lymphocyte ratio (MLR) was higher in men than in women (P < 0.01). The serum albumin (ALB) level was lower in patients with TB or TB exposure history than in those without TB history (P = 0.034). The prognostic nutritional index (PNI) was lower in patients with TB or TB exposure history than in those without tuberculosis history (P = 0.021). Patients with NTM lung disease were poorly treated.Conclusion: Clinical symptoms of the disease were not species-specific. Mycobacterium intracellulare and Mycobacterium avium strains were predominant in the Fuyang district of China. Previous TB or TB exposure history immensely enhanced the risk of NTM disease.Keywords: NTM, clinical symptoms, tuberculosis exposure history, bronchiectasis

WeiKang Shi,1 Lu Jin,2 AiHua Xu,2 Yu Gao,3 Na Zhang4 1Department of Dermatology, Jinhua Maternal and Child Health Care Hospital, Jinhua, Zhejiang Province, People’s Republic of China; 2Department of Nursing, Jinhua Central Hospital, Jinhua, Zhejiang Province, People’s Republic of China; 3Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Dermatology, Jinhua Central Hospital, Jinhua, Zhejiang Province, People’s Republic of ChinaCorrespondence: Na Zhang; Yu Gao, Email sallyzhang1986@163.com; gaoyu0570@163.comPurpose: Superficial Infantile hemangioma (SIH) is the most common type of IH. Some studies have shown the efficacy of 755-nm long pulse alexandrite laser (LPAL) and topical 2% carteolol hydrochloride (C-HCL) eye drops for the treatment of SIH. This article retrospectively analyzes the safety and efficacy of 755-nm LPAL combined with 2% C-HCL eye drops for treating thicker SIH, and explores the optimal treatment time for SIH.Materials and Methods: This study included 2– 5 mm thick SIH patients who received co-treatment of 755-nm LPAL and 2% C-HCL eye drops. The SIH patients were divided into 3 groups based on their age and IH growth curve: ≤ 1 month (≤ 1M), 1– 3 months (excluding 1 month; 1– 3M), and 3– 12 months (excluding 3 months; 3− 12M).Results: There was no difference in efficacy between the ≤ 1M and the 1– 3M group, and were both better than the 3– 12M group. Furthermore, there was no difference in the average number of treatments between the ≤ 1M and 1– 3M groups and were both less than the 3– 12M group. There was no significant difference in the incidence of adverse reactions between the groups. Compared with the ≤ 1M and 1– 3M groups, the 3– 12M group indicated more permanent skin lesions after the treatment.Conclusion: It was revealed that co-treatment with 755-nm LPAL and 2% C-HCL eye drops is safe and effective against thicker SIH. Compared with the 3– 12M group, ≤ 3 months can achieve better efficacy, requires a shorter treatment time, less likely to leave permanent skin lesions such as scars. Moreover, patients with no proliferation can be observed to 1 month.Keywords: infantile hemangioma, 755-nm long pulse alexandrite laser, 2% carteolol hydrochloride eye drops, treatment timing, efficacy

Chunrong Huang,1,2,&ast; Yulian Gao,1,2,&ast; Hongxia Lin,1– 3,&ast; Qinmei Fan,4,&ast; Ling Chen,1,2 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First People’s hospital of Jin Zhong, JinZhong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Chen; Yun Feng, Email co840608@hotmail.com; fy01057@163.comBackground: To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI).Methods: Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan–Meier analysis.Results: The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group.Conclusion: We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes. Keywords: Acinetobacter baumannii, bloodstream infection, mortality, prognostic predictors, multidrug-resistance

Caige Li,1,2 Yu Xue,1 Yiwei Liu,1 Kangning Zheng,1 Yuting Gao,1,3 Yi Gong,1 Junlan Lu,1 Yuman Zhang,1 Jingmin Ji,1 Zhiqin Zhang,1 Xinli Shi1 1Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of ChinaCorrespondence: Xinli Shi, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 3 Xingyuan Road, Shijiazhuang, Hebei, 050200, People’s Republic of China, Tel +86-0311-89926237, Email sxlsunshine@sina.comIntroduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1LKO could offer a protective effect in a liver injury model.Methods: Three-week-old Yap1LKO and Yap1Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1LKO and Yap1Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism.Results: Yap1LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD).Conclusion: Yap1LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet.Keywords: yes-associated protein, hepatocyte-specific Yap1 knockout, perilipin-2, lipidomic, triglyceride

Ying Wang,1,&ast; Xuelong Li,2,&ast; Yakun Gao,2 Xun Zhang,3 Yiyi Liu,3 Qing Wu1,3 1Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, Hefei Fourth People’s Hospital, Hefei, Anhui, People’s Republic of China; 2Qingdao Mental Health Center, Qingdao, Shandong, People’s Republic of China; 3School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wu, Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, 316 Huangshan Road, Hefei, 230022, People’s Republic of China, Tel +86-13856919530, Email wuqinghf@163.comPurpose: The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD.Patients and Methods: A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital’s electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings.Results: The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P< 0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P< 0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049− 39.21), BMI (OR=1.398, 95% CI=1.306− 1.497), triglycerides (OR=1.456, 95% CI=1.036− 2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110− 0.672) were risk factors for NAFLD (all P< 0.05).Conclusion: Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.Keywords: China, comorbidity, Psychiatry

Shangyu Luo,1 Xueqin Hu,2 Yunjun Hong,1 Yunchun Gao,1 Xianglin Liu,1 Yu Peng,1 Xueqing Tong,3 Xiaobo Zhang,1 Jun Wen1 1Department of Neurology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 2Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 3Department of Brain Electrophysiology, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde City, Hunan Province, People’s Republic of ChinaCorrespondence: Xiaobo Zhang; Jun Wen, Fax +86 0736 7788009 ; +86 0736 7788010, Email 285058041@qq.com; cdwenjun1973@163.comPurpose: Research on post-stroke depression (PSD) following the lifting of coronavirus disease 2019 (COVID-19) restrictions remains sparse. This study aimed to investigate the factors associated with PSD after the easing of COVID-19 restriction measures.Patients and Methods: This cross-sectional study was conducted with 947 stroke patients (cerebral hemorrhage and cerebral infarction) meeting the inclusion criteria. Participants completed a demographic questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Additionally, data were collected on C-reactive protein (CRP), homocysteine (Hcy), modified Rankin Scale (mRS), stroke site, National Institutes of Health Stroke Scale (NIHSS), thyroid-stimulating hormone (TSH), and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. This study assessed correlations between these indices and PSD.Results: Stroke patients with a PHQ-9 score ≥ 5 were identified as having PSD, with a prevalence rate of 14.15%. No significant correlation was found between previous COVID-19 infection and PSD. However, multiple regression analysis revealed associations between PSD and the following factors: TSH (OR: 0.87, 95% CI: 0.76– 1), CRP levels (OR: 1.01, 95% CI: 1– 1.02), family history of stroke (OR: 4.25, 95% CI: 1.66– 10.88), migraine history (OR: 8.63, 95% CI: 2.49– 29.85), and shorter sleep duration (OR: 0.6, 95% CI: 0.51– 0.71) (all P

Fei Qi,1– 3 Yimeng Gao,1– 3 Hongzhong Jin1– 3 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Beijing, People’s Republic of China; 3National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of ChinaCorrespondence: Hongzhong Jin, Peking Union Medical College Hospital (Dongdan Campus), No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 10 6915 1500, Email jinhongzhong@263.netBackground: Livedoid vasculopathy is an uncommon cutaneous ulcerative dermatosis that is challenging to diagnose. Diagnostic delay brought both pain and uncurable atrophied scar to patients.Purpose: We conducted this study to identify the factors responsible for the initial misdiagnosis of livedoid vasculopathy and to identify possible methods to increase the diagnostic accuracy of livedoid vasculopathy.Patients and Methods: We conducted a retrospective medical record review to confirm the diagnosis of livedoid vasculopathy in patients who visited the Department of Peking Union Medical College Hospital for the first time. We used the Diagnosis Error Evaluation and Research taxonomy to evaluate missed cases.Results: Twenty-three patients (85.18%) had an alternate diagnosis, including 10 (43.4%) with two or more diagnoses. The average time from disease onset to the final diagnosis of livedoid vasculopathy was 4.61 ± 0.69 years. The major diagnostic errors were clinician assessment failures and failures in the timely follow-up and rechecking of patients. Allergic vasculitis was the most common misdiagnosis. Other alternate diagnoses include Henoch-Schoenlein purpura, pigmented purpuric dermatosis, eczema, erythema nodosum, and reactive perforating collagenases. Twenty-three patients (65.21%) received systemic corticosteroid therapy before the final diagnosis of livedoid vasculopathy.Conclusion: It is critical to raise the awareness of clinicians about livedoid vasculopathy, especially when patient present with extensive livedo racemosa or long-lasting purpuric lesions on the lower limbs. Long-term follow-up is necessary, especially for younger patients. Skin biopsy is recommended before systematic therapy.Keywords: livedoid vasculopathy, atrophie blanche, diagnostic accuracy, vasculitis

Ziwei Jiang,&ast; Lianglong Chen,&ast; Lei Huang, Shengxiang Yu, Jiabao Lin, Mengyao Li, Yanbin Gao, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.Keywords: endogenous stem cell homing, in situ tissue regeneration, biomimetic design, wound healing, bioactive materials

Nan Tang,1 Mengyue Pei,2 Huihui Liu,3 Jingru Chen,1 Youting Wang,1 Lei Xie,4 Junping Hu,3,5 Jing Wang,6 Yuan Gao1 1Department of Nursing, 1st Medical Centre of PLA General Hospital, Beijing, People’s Republic of China; 2School of Medicine, Henan Kaifeng College of Science Technology and Communication, Kaifei, Henan Province, People’s Republic of China; 3School of Nursing, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 4Renji Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 6Department of Gynecology, 1th Medical Centre of PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang; Yuan Gao, Email wangjing353535@163.com; gaoyuanzd@163.comBackground: The purpose of this study was to explore the relationship between infertility-related stress and dyadic coping with quality of life (QoL) in couples with infertility issues, and verify gender differences and dyadic interactions in the associations between them.Methods: This cross-sectional study included 340 couples who were recruited from the First Affiliated Hospital of Lanzhou University between March 2022 and November 2022. The Fertility Problem Inventory, Dyadic Coping Inventory and FertiQoL were used to measure infertility-related stress, dyadic coping and QoL. The Actor-Partner Interdependence Model was used to analyze the effects of infertility-related stress and dyadic coping on the couple’s own QoL (actor effect) as well as on their partner’s QoL (partner effect).Results: Female patients perceived significantly lower levels of QoL and dyadic coping than those of husbands. There was no statistically significant difference in the infertility-related stress between wives and husbands. Husbands’ infertility-related stress had actor and partner effects on their own and their wives’ QoL, while wives’ infertility-related stress only had an actor effect on their own QoL. Husbands’ dyadic coping had both actor effect and partner effects on their own and their wives’ QoL, meanwhile wives’ dyadic coping had both actor effect and partner effects on their own and their husbands’ QoL.Conclusion: Husbands’ QoL was impacted by their own infertility-related stress, dyadic coping and their wives’ dyadic coping. Whereas wives’ QoL was influenced by infertility-related stress and dyadic coping from both their own and their spouses. Therefore, elevating the level of dyadic coping may contribute to improving QoL for both husbands and wives. Moreover, enhancing the ability to cope with infertility-related stress might be useful for husbands and indirectly contribute to wives’ QoL.Keywords: infertility, couple, infertility-related stress, dyadic coping, QoL

Jiajin Feng,1,&ast; Keming Chen,1,&ast; Haifu Tian,1 Al-qaisi Mohammed Abdulkarem,1 Yunshang Tuo,1 Xuehao Wang,1 Bincheng Huang,1 Yu Gao,1 Zhiyong Lv,1 Rui He,2 Guangyong Li1 1General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyong Li, Email guangyongli1979@hotmail.comObjective: To explore the effectiveness of prostate biopsy density in predicting prostate cancer under cognitive and systematic biopsy mode in multi-parametric magnetic resonance imaging (mpMRI).Methods: A retrospective analysis was conducted on clinical data of 204 patients who were suspected of having prostate cancer with prostate-specific antigen (PSA) levels less than 50 ng mL− 1 and underwent cognitive and systematic biopsy through the perineal approach in our hospital from 2022 to 2023. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratios of prostate biopsy density and relevant clinical indicators. Logistic regression analysis was performed to establish a predictive model combining indicators with predictive value. The predictive value of each indicator and the new model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).Results: The detection rate of prostate cancer in the study population was 32.35%. Multivariate analysis showed that age, PSAD, PI-RADS 2.1 score, and prostate biopsy density were independent predictors of prostate cancer. The ROC curve analysis revealed an AUC of 0.707 (95% CI 0.625– 0.790) for biopsy density, with a cutoff value of approximately 0.22 needle mL− 1. The best predictive model consisted of age, PSAD, PI-RADS 2.1 score, and biopsy density, with an AUC of 0.857.Conclusion: Biopsy density is associated with the detection of prostate cancer, with a critical value of 0.22 needle mL− 1. Combining biopsy density with other clinical indicators can significantly improve the ability to predict prostate cancer and avoid unnecessary prostate biopsy cores.Keywords: prostate biopsy, multi-parametric magnetic resonance imaging, biopsy density, cognitive fusion, cancer prediction

Yuqing Li,1,&ast; Lei Wu,1,2,&ast; Rui Zhao,1,2,&ast; Yi Gao,1 Geng Bai,1 Ziqiang Guo,1 Xiaolin Chen,1 Yuanlu Chen,2 Tong Liu,1 Guangping Li1 1Tianjin Key Laboratory of Logic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 2TEDA International Cardiovascular Hospital, Electrophysiological Department, Tianjin, 300457, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangping Li, Email tic_tjcardiol@126.comBackground: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA.Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL.Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems.Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.Keywords: electrocardiogram, inferior wall myocardial infarction, percutaneous coronary intervention, right coronary artery

Fangyuan Kuang,1,2 Yang Gao,3 Qingyun Zhou,4 Chenying Lu,3 Qiaomei Lin,4 Abdullah Al Mamun,5 Junle Pan,6 Shuibo Shi,7 Chaoyong Tu,4,&ast; Chuxiao Shao2,&ast; 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, People Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui, Zhejiang, 323000, People’s Republic of China; 3Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 5Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6First Academy of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7The First Clinical Medical College of Nanchang University, Nanchang City, Jiangxi, 330000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoyong Tu, Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China, Email tcy7409@163.comBackground: A limited number of studies have examined the use of radiomics to predict 3-year overall survival (OS) after hepatectomy in patients with hepatocellular carcinoma (HCC). This study develops 3-year OS prediction models for HCC patients after liver resection using MRI radiomics and clinicopathological factors.Materials and Methods: A retrospective analysis of 141 patients who underwent surgical resection of HCC was performed. Patients were randomized into two set: the training set (n=98) and the validation set (n=43) including the survival groups (n=111) and non-survival groups (n=30) based on 3-year survival after hepatectomy. Furthermore, x2 or Fisher’s exact test, univariate and multivariate logistic regression analyses were conducted to determine independent clinicopathological risk factors associated with 3-year OS. 1688 quantitative imaging features were extracted from preoperative T2-weighted imaging (T2WI) and contrast-enhanced magnetic resonance imaging (CE-MRI) of arterial phase (AP), portal venous phases (PVP)and delay period (DP). The features were selected using the variance threshold method, the select K best method and the least absolute shrinkage and selection operator (LASSO) algorithm. By using Bernoulli Naive Bayes (BernoulliNB) and Multinomial Naive Bayes (MultinomialNB) classifiers, we constructed models based on the independent clinicopathological factors and Rad-scores. To determine the best model, receiver operating characteristics (ROC) and Delong’s test were used. Moreover, calibration curves were used to determine the calibration ability of the model, while decision curve analysis (DCA) was implemented to evaluate its clinical benefit.Results: The fusion model showed excellent prediction precision with AUC of 0.910 and 0.846 in training and validation set and revealed significant diagnostic accuracy and value in the calibration curve and DCA analysis.Conclusion: Nomograms based on MRI radiomics and clinicopathological factors have significant predictive value for 3-year OS after hepatectomy and can be used for risk classification.Keywords: hepatocellular carcinoma, hepatectomy, MRI radiomics

Ying Gao,1,2 Jie Hao,1 Zhendong Zhang1 1Department of Breast and Thyroid Surgery, Tianjin Union Medical Center, Tianjin, 300121, People’s Republic of China; 2Department of Thyroid and Neck Cancer, Tianjin Medical University Cancer Hospital, National Cancer Clinical Research Center, Tianjin Cancer Clinical Research Center, Tianjin Key Laboratory of Cancer Prevention and Treatment, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Zhendong Zhang; Jie Hao, No. 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +8613302182253 ; +8618920392330, Email zhangzhendongdoc@sina.com; haojie1215@126.comAbstract: Decision-making regarding adjuvant chemotherapy for older adults with breast cancer is a challenge because older adult patients often have poor physical health, frailty, and age-related comorbidities, which can compromise treatment outcome. Due to these considerations, doctors tend to use less chemotherapy for breast cancer in older adults. However, older patients in good general health could still benefit from chemotherapy. Careful benefit-risk assessment is essential to provide best care for each older adult patient. Due to a rapidly aging population, breast cancer in older adults is becoming a serious public health issue in China. In this mini review, we discuss the need, means, and tools to assess the benefits and risks of adjuvant chemotherapy in older adults with breast cancer. The contents of this review may drive decision-making with regard to the use and selection of adjuvant chemotherapy for older adult patients in China who are fit for the treatment.Keywords: breast cancer, older adult patients, chemotherapy, assessment

Cuiting Wang,1,2 Tian An,1,2 Cong Lu,1,2 Tiantian Liu,1,2 Xiaomeng Shan,1,2 Zhiyao Zhu,1,2 Yanbin Gao1,2 1School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of TCM Collateral Disease Theory Research, Beijing, People’s Republic of ChinaCorrespondence: Yanbin Gao; Zhiyao Zhu, School of Traditional Chinese Medicine, Capital Medical University, No. 10 You An Men Wai, Xi Tou Tiao, Feng Tai District, Beijing, 100069, People’s Republic of China, Tel +86 10 8391 1640 ; +86 10 8391 1626, Email gyb@ccmu.edu.cn; 20120103@ccmu.edu.cnBackground: Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated.Purpose: The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism.Methods: After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR.Results: Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO2 and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment.Conclusion: TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue. Keywords: traditional Chinese medicine, Tangzhiping, prediabetes, adipose tissue, inflammation, lipolysis

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

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Ji-Cong Jiang,&ast; Ying-Wei Wang,&ast; Yu Gao, Qi-Shuang Zhou Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi-Shuang Zhou; Yu Gao, Email 15258672597@163.com; gaoyu0570@sina.comBackground and Objective: Nevus of Ota (NO), also known as “brownish-blue nevus of the palate of the eye”, is a benign dermal pigmentation that increases skin disease. The Q-switched ruby laser is a classic treatment for nevus of Ota in children, but the optimal age for treatment is still controversial. The aim of this study was to investigate the treatment effect of Q-switched ruby laser in children with nevus of Ota at different ages and the effect on psychological health status.Materials and Methods: Children with nevus of Ota treated with Q-switched ruby laser in the Department of Dermatology of the Second Affiliated Hospital of Wenzhou Medical University from June 2015 to June 2019 were retrospectively analysed. And the mental health status was assessed using the CDI scale.Results: In the preschool children group (0– 7 year age), the significant efficacy rates was 93.1%, the average number of treatments was 3.6, and the overall incidence of adverse reactions was 4.7%. The significant efficacy rates in the school-age children group (7– 14 year age) was 90.3%, the average number of treatments was 5.1, and the overall incidence of adverse reactions was 13.7%. The mean post-treatment CDI score in the preschool children group was 10.8, and 9.7% of children exceeding 19 points. The mean pre-treatment CDI score in the school-age children group was 17.3, and 24.6% of children exceeding 19 points. The mean post-treatment CDI score was 13.6 and 15.1% of children exceeded 19 points. The chi-square test for the significant efficacy rate of the two groups showed P> 0.05, which was not statistically significant. The significant efficacy rate of the preschool group and that of the school-age children group. The t-test for the number of treatments in the two groups showed P< 0.05, which was statistically significant. Adverse reactions in the two groups showed a statistically significant P< 0.05. The mean CDI scores and the percentage of depressed individuals in the school-age children group were significantly lower after treatment than before treatment (p< 0.05).Conclusion: Q-switched ruby laser is safe and effective in treating nevus of Ota in children. Early treatment can reduce the number of treatments and the incidence of adverse reactions. In addition, early treatment can reduce children’s depression, which is beneficial to mental health.Keywords: nevus of Ota, children, Q-switched ruby laser, early treatment, mental health

Qianhui Zhou,1 Yi Liu,1 Yan Gao,1 Lingli Quan,1 Lin Wang,1 Hao Wang2 1Department of Respiratory and Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, 412000, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, HengYang, Hunan, 421005, People’s Republic of ChinaCorrespondence: Hao Wang, Email wanghao872013@163.comBackground: Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs.Methods: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results.Results: 7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis.Conclusion: The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.Keywords: lung adenocarcinoma, tumor mutation load, cuproptosis, long noncoding RNA, immunotherapeutic response

Zhanying Sun,1,2,&ast; Jie Song,2,&ast; Jingru Chen,1 Xueyang Gan,1 Yi Li,3 Chen Qiu,2 Weili Zhang,1 Yuan Gao2 1Graduate School, Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 2Nursing Department, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Orthopedics, the Forth Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Gao, Email gaoyuanzd@163.comPurpose: Resilience is considered as a protective factor that can assist individuals to reduce post-traumatic stress reactions. In recent years, armies in many countries have widely implemented resilience training programs before deployment to prevent or reduce post-deployment combat stress reactions. Therefore, this study aims to review what is known about resilience interventions for military personnel in pre deployment.Methods: Based on Arskey and O’Malley’s framework, a scoping review was completed. This review was performed through searching databases including PubMed, Embase, Web of Science, Medline and the Cochrane Library, and screening literature to extract data, finally summarizing the findings.Results: A total of 25 studies focusing on resilience interventions for military personnel in pre deployment were involved and analyzed using intervention approaches, outcome measures, intervention effects, and so on.Conclusion: Based on the existing evidence in this review, it is cautiously believed that the resilience intervention program for military personnel before deployment is effective. However, there is no single effective best method even the same type intervention can make different effects in different situations and populations. Therefore, the population differences and context should be fully considered in constructing and implementing program to build military personnel resilience.Keywords: resilience, military personnel, prevention, post-traumatic stress response

Zheping Chen,1,&ast; Changli Gao,1,2,&ast; Yingchao Zhang,1,3 Yongxu Gao,1,4 Le Zhang,1 Shanshan Zhao,1 He Zhang,1 Xin Zhao,1 Yanwu Jin1 1Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Anesthesiology, Laoling People Hospital, Laoling, People’s Republic of China; 3Department of Anesthesiology, Shouguang People Hospital, Weifang, People’s Republic of China; 4Department of Anesthesiology, Jinan Third People’s Hospital, Laoling, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanwu Jin, Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Bei Yuan Street, Jinan, 250033, People’s Republic of China, Tel +86-17660085535, Email jinyanwu_aa@163.comBackground: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine.Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 μg·kg− 1 (RD0.5 Group) or 1.0 μg·kg− 1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 μg·kg− 1·h− 1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery.Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness.Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 μg·kg− 1) may be a more appropriate choice.Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).Keywords: dexmedetomidine, thoracic paravertebral nerve block, neuropathic pain, thoracoscopic surgery

Yu Gao,1 Yuechi Sun2 1School of Psychology, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2School of Economics and Management, China University of Geosciences (Beijing), Beijing, People’s Republic of ChinaCorrespondence: Yu Gao, School of Psychology, Shandong Second Medical University, 7166 Baotong West Street, Weicheng District, Weifang, Shandong, 261053, People’s Republic of China, Email gaoyucugb@163.comBackground: Public health emergencies not only threaten the physical and mental health of the public but also trigger a series of risky behaviors of the public, which in turn lead to the emergence or intensification of risk events, disrupting existing economic and social order.Purpose: Based on construal level theory, cognitive appraisal theory of emotions and mood maintenance hypothesis, the study aims to investigate the collectively effect of risk perception and psychological insecurity in the connection between psychological distance and public risky behavior.Participants and Methods: Cross-sectional data was derived from 257 China urban residents. All participants finished the psychological distance scale, risk perception scale, psychological insecurity scale, and risky behavior scale. The research hypothesis was tested using the PROCESS macro.Results: The direct impact of psychological distance on risky behavior was not significant (β=− 0.018, p> 0.05). The indirect impact of psychological distance on risky behavior was significant. In other words, the impact of psychological distance on risky behavior was serially mediated via risk perception and psychological insecurity (β=0.011, 95% CI= [0.0013, 0.025]).Conclusion: Risk perception and psychological insecurity play serial mediating roles in the relationship between psychological distance and public risky behavior. We conclude that during public health emergencies, public health managers should pay extra attention to the risk perception and psychological insecurity level of the public with closer psychological distance, take measures to reduce their risk perception, enhance their psychological security, and reduce their risky behavior, thereby ensuring the physical and mental health of the public and maintaining the stability of economic and social order.Keywords: public health emergencies, psychological distance, risk perception, psychological insecurity, risky behavior

Songtao Yang, Jie Cao, Ying Wang, Qi Chen, Fangyu Li, Yuanyuan Gao, Rui Li, Li Yuan Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Li Yuan, Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email yuanli18cn@126.comBackground: The “gut-islets axis” is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets β-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the “gut-islet axis.”.Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets β cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2.Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by β-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets β-cell function and β-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces β-cell pyroptosis.Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and β cell pyroptosis, thereby restoring islets β cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.Keywords: exosomes, ACE2, islets β cell, the NLRP3 inflammasome

Liying Ma,1,2 Yansong Gao,1 Ge Yang,1 Lei Zhao,2 Zijian Zhao,1 Yujuan Zhao,1 Yuhang Zhang,2 Shenhui Li,2 Shengyu Li1 1Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun, 130033, People’s Republic of China; 2School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of ChinaCorrespondence: Shengyu Li, Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), No. 1363 Sheng-Tai Street, Changchun, Jilin Province, 130033, People’s Republic of China, Tel +86 431 87063289, Fax +86 431 87063075, Email lisy720@126.comAim: The inflammatory response plays a pivotal role in the occurrence, progression, and plaque formation of atherosclerosis. The study was performed to investigate the impacts of notoginsenoside R1 on the development of atherosclerosis (AS) and the potential mechanisms.Methods: Rats induced with AS by a high-fat-diet and vitamin D3 were treated with notoginsenoside R1 for six weeks. The ameliorative effect of NR1 on AS rats was assessed by detecting pathological changes in the abdominal aorta, biochemical indices in serum and protein expression in the abdominal aorta, as well as by analysing the gut microbiota.Results: The NR1 group exhibited a noticeable reduction in plaque pathology. Notoginsenoside R1 can significantly improve serum lipid profiles, encompassing TG, TC, LDL, ox-LDL, and HDL. Simultaneously, IL-6, IL-33, TNF-α, and IL-1β levels are decreased by notoginsenoside R1 in lowering inflammatory elements. Notoginsenoside R1 can suppress the secretion of VCAM-1 and ICAM-1, as well as enhance the levels of plasma NO and eNOS. Furthermore, notoginsenoside R1 inhibits the NLRP3/Cleaved Caspase-1/IL-1β inflammatory pathway and reduces the expression of the JNK2/P38 MAPK/VEGF endothelial damage pathway. Fecal analysis showed that notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as Firmicutes and Proteobacteria) and increasing the quantity of probiotic bacteria (such as Bacteroidetes).Conclusion: Notoginsenoside R1, due to its unique anti-inflammatory properties, may potentially prevent the progression of atherosclerosis. This mechanism helps protect the vascular endothelium from damage, while also regulating the imbalance of intestinal microbiota, thereby maintaining the overall health of the body. Keywords: notoginsenoside R1, inflammation, endothelial damage, gut microbiota

Kaiyu Wang,1,&ast; Yan Gao,1,&ast; Shan Wu,1,&ast; Jin Zhang,1 Manfang Zhu,2 Xiayu Chen,1 Xizi Fu,1 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.comBackground: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.Keywords: mRNA gene therapy, dual-mRNA delivery, tumor cell lysates, Bim and IL-23A mRNAs, immune response

Zhihao Zhao,1,&ast; Diya Qi,1,&ast; Zeqing Zhang,2,&ast; Xin Du,3 Fengyun Zhang,2 Ruicong Ma,4 Yi Liang,1 Yuewu Zhao,1 Ying Gao,1 Yu Yang2 1Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 4Graduate School, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China, Tel +86-13951461302, Email xzyygaoying@163.com Yu Yang, Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86-15651359875, Email xuzhouyangyu@163.comPurpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF).Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor.Results: The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission.Conclusion: Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.Keywords: heart failure with preserved ejection fraction, inflammation, cytokine, readmission, risk assessment

Yuanfei Li,1,&ast; Yong Yang,1,&ast; Yafeng Zheng,2,&ast; Yang Gao,3 Guoliang Shu,4 Wei Gai,2 Yuxin Guo,2 Xianghui Deng1 1Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 2WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 3Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 4Department of General Surgery, 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: Xianghui Deng, Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China, Tel +8613974833075, Email 853275395@qq.comAbstract: The liver receives blood from both the hepatic artery and portal vein. Hepatic infarction is rare in clinical practice as both the hepatic artery and portal vein can supply blood to the liver. Here, we reported a case of a 75-year-old man who underwent radical laparoscopic surgery for rectal cancer and subsequently developed hepatic infarction. The patient experienced severe infection, as well as circulatory and respiratory failure on the third day after surgery. The patient presented with high fever, chest tightness, shortness of breath, decreased blood oxygen saturation and blood pressure. The leukocyte count decreased from 8.10 × 10^9/L to 1.75 × 10^9/L. Procalcitonin (PCT) levels increased from 1.02 ng/mL to 67.14 ng/mL, and eventually reaching levels over 200 ng/mL. Enhanced abdominal computed tomography (CT) confirmed the presence of hepatic infarction, but no thrombosis was observed in the hepatic artery or portal vein. Metagenomic next-generation sequencing (mNGS) identified hypervirulent Klebsiella pneumoniae (hvKp) in the patient’s blood and ascites, one day earlier than the detection results using traditional culture methods. The patient was diagnosed with hepatic infarction combined with septic shock caused by hvKp. This case emphasizes that in the high-risk group of thrombosis, infection can trigger exacerbated hepatic infarction events, particularly in cases after surgical procedures. For severely ill patients with infectious diseases who are admitted to the ICU with worsening symptoms, it is important to collect appropriate samples and send them for pathogen detection using mNGS in a timely manner. This may aid in early intervention and improve clinical outcomes.Keywords: hepatic infarction, mNGS, hypervirulent Klebsiella pneumoniae, septic shock

Fei Qi, Yimeng Gao, Hongzhong Jin Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hongzhong Jin, Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, People’s Republic of China, Tel +86-10-69151500, Email jinhongzhong@263.netAbstract: The application of biologics such as anti-tumor necrosis factor (TNF) has shown great efficacy in livedoid vasculopathy (LV). However, new biological options need to be identified for those with a high tuberculosis reactivation risk. In this study, we evaluated the efficacy of anti-17A biologics for LV therapy. Two patients with LV who were irresponsive to traditional anticoagulation therapy were studied at the outpatient dermatology clinic of Peking Union Medical College Hospital. All patients received anti-17A biological therapy for at least two–four weeks. Both patients reported an exacerbation of the skin lesions, which might indicate that the IL-17 pathway plays a critical role in LV pathogenesis.Keywords: livedoid vasculopathy, biologic therapy, TNF-alpha, IL-17, atrophied blanched

Aguo Cheng,1,2 Suohui Zhang,1,3 Fanda Meng,4 Mengzhen Xing,5 Han Liu,3 Guozhong Yang,3 Yunhua Gao1– 3 1Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry of Chinese Academy of Sciences, Beijing, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Beijing CAS Microneedle Technology Ltd, Beijing, People’s Republic of China; 4School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 5Key Laboratory of New Material Research Institute, Department of Pharmaceutical Research Institute, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Yunhua Gao, Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry of Chinese Academy of Sciences, Beijing, People’s Republic of China, Tel +86 (10)82543581, Email yhgao@mail.ipc.ac.cnPurpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum’s barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility.Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance.Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action’s duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1β compared with the methotrexate subcutaneous injection method.Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration. Keywords: nanosuspension, highly lipophilic drugs, dissolving microneedle, cannabidiol, knee synovitis

Yuli Ji,1,2,&ast; Liangyu Mi,1,2,&ast; Miaomiao Zhao,1,2 Xiaoyao He,1,2 Yuting Hu,1,2 Yanan Gao,1,2 Chengliang Yin,3 Ke Xu1,2 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Xu, Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, Shanxi Province, People’s Republic of China, Email xukesxbqeh@hotmail.comAbstract: Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.Keywords: engineered exosomes, autoimmune diseases, genetic engineering, anti-inflammatory applications

Yu Gao,1 Haiyan Liu,2 Yuechi Sun2 1School of Psychology, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2School of Economics and Management, China University of Geosciences (Beijing), Beijing, People’s Republic of ChinaCorrespondence: Haiyan Liu, School of Economics and Management, China University of Geosciences (Beijing), 29 Xueyuan Road, Haidian District, Beijing, 100083, People’s Republic of China, Email liuhy@cugb.edu.cnBackground: In the digital age, people’s attitudes and psychological security towards public health emergencies will be shared. Similar or identical psychological security states are prone to clustering and differentiation, while differentiated group psychological security is more prone to polarization, leading to group psychological security risks and then posing a threat to social stability and national security. However, existing studies mostly use qualitative analysis methods to study group emotional risks. There are still limitations in the study of dynamics of group psychological security risks through mining real data of social media.Purpose: The study aims to use intelligent analysis methods to understand how group psychological security risks dynamically change.Methods: The study draws on text sentiment analysis, Markov chains and time series analysis to construct a framework for the evolution of group psychological security risks. Based on this framework, text data was crawled on Sina Weibo platform, mainly consisting of posts during public health emergencies (March 1st to June 30th, 2022) in Shanghai, and a psychological security lexicon in the field of public health emergencies was constructed. This laid the foundation for identifying the tendencies, intensity, and transitions of individual text psychological security, and then exploring the evolution trend of group psychological security risks.Results: Compared with the generation and reduction periods, group psychological security risks are more likely to occur during the outbreak and recovery periods, and the intensity level is also higher. The overall intensity of group psychological security risks shows an evolution trend of first increasing, then decreasing, and then increasing again.Conclusion: The paper provides an opportunity to explore the dynamics of psychological security in the digital space. Meanwhile, we call on the government and relevant management departments to pay more attention to the group psychological security risks formed during the outbreak and recovery periods of public health emergencies, and take corresponding measures in a timely manner to guide the public to transform the extreme psychological security state into the normal psychological security state, in order to prevent and resolve group psychological security risks, promote social stability and national security.Keywords: group psychological security risks, psychological security lexicon, machine learning, evolution trend

Chen Yang,1,2,&ast; Wangjun Dong,2,&ast; Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128&num; Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Xin Zhao,1,2 Guijiang Huang,2 Zhenrong Xie,2 Yaxiong Mo,3 Hongxuan Zhu,2 Yajie Gao,2 Yanbing Han,4 Wei Tang2 1Department of Pharmacy, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, People’s Republic of China; 2Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Wei Tang, Department of Science and Education, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email tangw666@sina.com Yanbing Han, Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China, Email ynhyb@163.comIntroduction: Neuregulin-1 (NRG-1) appears to play a role in the pathogenesis of several neuropsychiatric disorders, including epilepsy. We conducted a study to investigate the effect of anti-seizure medication on NRG-1 mRNA and NRG-1 protein levels in patients with first-episode focal epilepsy.Methods: The levels of NRG-1 mRNA isoforms (type I, II, III, and IV) in peripheral blood mononuclear cells (PBMCs) of 39 healthy controls, 39 first-episode focal epilepsy patients before anti-seizure medication (ASM) therapy and four weeks after administration of ASM were measured by RT-qPCR, and the levels of NRG-1 protein in the serum of samples of each group were determined using ELISA. In addition the relationship between efficacy, NRG-1 mRNA expression, and NRG-1 protein expression was analyzed.Results: The levels of NRG-1 mRNA progressively increased in patients with first-episode focal epilepsy treated with ASM and were distinctly different from those before medication, but remained lower than in healthy controls (all P < 0.001). Before and after drug administration, NRG-1 protein levels were substantially higher in epileptic patients than in healthy controls, and no significant changes were detected with prolonged follow-up (P < 0.001). Patients with epilepsy who utilized ASM were able to control seizures with an overall efficacy of 97.4%. There was a negative correlation between NRG-1 mRNA levels and efficacy: as NRG-1 mRNA levels increased, seizures reduced (all P < 0.05).Conclusion: Our research indicated that NRG-1 may play a role in the pathophysiology of epilepsy. NRG-1 mRNA may provide ideas for the discovery of novel epilepsy therapeutic markers and therapeutic targets for novel ASM.Keywords: neuregulin-1, focal epilepsy, drug treatment, pathophysiology

Yanxia He,1,&ast; Zhumei Luo,1,&ast; Haoqing Chen,2,3,&ast; Liqing Ping,2,3 Cheng Huang,2,3 Yan Gao,2,3 Huiqiang Huang2,3 1Department of Oncology, The Third People’s Hospital of Chengdu, Sichuan, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiang Huang; Yan Gao, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China, Email huanghqsysucc@163.com; gaoyan@sysucc.org.cnBackground: Systemic inflammation, immunity, and nutritional status are closely related to patients’ outcomes in several kinds of cancers. This study aimed to establish a new nomogram based on inflammation-immunity-nutrition score (IINS) to predict the prognosis of extranodal natural killer/T-cell lymphoma (ENKTL) patients.Methods: The clinical data of 435 patients with ENTKL were retrospectively reviewed and randomly assigned to training cohort (n=305) and validation cohort (n=131) at a ratio of 7:3. Cox regression analysis was employed to identify independent prognostic factors and develop a nomogram in the training cohort. Harrell’s concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) curve were employed to assess the performance of the nomogram and compare it with traditional prognostic systems (PINK, IPI, KPI). Internal validation was performed using 1000 bootstrap resamples in the validation cohort. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) of patients in different risk groups.Results: In the training cohort, in addition to several classic parameters, IINS was identified as an independent prognostic factor significantly associated with the OS of patients. The nomogram established based on the independent prognostic indicators showed superior survival prediction efficacy, with C-index of 0.733 in the training cohort and 0.759 in the validation cohort compared to the PINK (0.636 and 0.737), IPI (0.81 and 0.707), and KPI (0.693 and 0.639) systems. Furthermore, compared with PINK, IPI, and IPI systems, the nomogram showed relatively superior calibration curves and more powerful prognostic discrimination ability in predicting the OS of patients. DCA curves revealed some advantages in terms of clinical applicability of the nomogram compared to the PINK, IPI, and IPI systems.Conclusion: Compared with traditional prognostic systems, the nomogram showed promising prospects for risk stratification in ENKTL patient prognosis, providing new insights into the personalized treatment.Keywords: inflammation-immunity-nutrition score, extranodal natural killer/T-cell lymphoma, nomogram, prognosis, overall survival

Jiechu Wang,1– 3,&ast; Yao Yu,1,&ast; Ya Gao,1– 3,&ast; Tingting Wan,1– 3 Zhukai Cong,1– 3 Zhengqian Li,1– 3 Yang Zhou,1– 3 Xiaoxiao Wang,4 Luyang Feng,1– 3 Yongzheng Han,1– 3 Jing Zhang,1– 3 Yinyin Qu,1– 3 Xiangyang Guo1– 3 1Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Anesthesia and Perioperative Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care (CPAM), Beijing, 100191, People’s Republic of China; 4Research Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo; Yinyin Qu, Department of Anesthesiology, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn; quyinyin@bjmu.edu.cnBackground: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists’ understanding of MH in China.Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants’ perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P< 0.001), hospital classification (P< 0.001), and urban hierarchy (P< 0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.Keywords: malignant hyperthermia, dantrolene, China, anesthesiologists, survey