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Xiaolu Chen,1– 3 Jian Liu,1,2 Guizhen Wang,1,2 Yanqiu Sun,1,2 Xiang Ding,1– 3 Xianheng Zhang1– 3 1Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86 551 62838582, Fax +86 551 62821605, Email liujianahzy@126.comObjective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism.Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of “active component-target-disease” was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP’s delay of immune inflammation in OA.Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway.Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.Keywords: osteoarthritis, chondrocytes, inflammation, LncRNA HOTAIR/APN/PI3K/AKT

Zhenyu Li,1 Jimin Liu,2 Haishan Cui,3 Wenlong Qi,4 Yangyang Tong,4 Tan Wang4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 2Department of Respiratory, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 3Department of Traditional Chinese Medicine, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 4Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of ChinaCorrespondence: Tan Wang, Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of China, Email wangtan0215@163.comAbstract: The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.Keywords: non-small cell lung cancer, Astragalus membranaceus, antitumor activity, immunoregulation, cisplatin

Kaifei Chu,1,2,* Jie Liu,2,* Xu Zhang,1,2 Minran Wang,1 Wanping Yu,1 Yuyue Chen,1 Lingling Xu,2 Geng Yang,1 Naru Zhang,1 Tiejun Zhao1,2 1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, People’s Republic of China; 2College of Life Sciences, Zhejiang Normal University, Jinhua, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiejun Zhao; Naru Zhang, Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email tjzhao@hzcu.edu.cn; zhangnr@hzcu.edu.cnAbstract: Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs.Keywords: herbal medicine, plant-derived exosome-like nanovesicles, extracellular vesicles, cancer treatment, nanomedicine

Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

Ning-ning Xia, Kuei-ching Pan, Jing Liu, Daxi Ji Department of Nephrology, Nanjing BenQ Medical Center, BenQ Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Kuei-ching Pan; Jing Liu, Email PKJ13951672501@126.com; liujing66382@126.comObjective: To investigate current status of quality of life and the association between depression and symptom burden in a sample of Chinese maintenance hemodialysis (MHD) patients.Methods: A self-designed patient general information questionnaire, disease-related information questionnaire, dialysis patient symptom burden scale, depression scale, and quality of survival scale were used to investigate 380 maintenance haemodialysis patients in haemodialysis centres. A regression model of the factors affecting the quality of survival was established using structural equation modelling.Results: The regression model data had a high goodness of fit: c2/df = 4.736, RMSEA = 0.099, GFI = 0.918, CFI = 0.972, TLI = 0.962, SRMR = 0.0469. Structural equation model analysis showed that depression had a positive predictive effect on symptom burden, β = 0.398, P

Shuang Du,1,&ast; Ke Lin,2,&ast; Jing Li,3 Xin Zhou,4 Chaolan Wang,2 Jun Liu,3 Na Li,2 Jian Chen2 1Department of Rehabilitation Medicine, The First People’s Hospital of Jin Tang County, Chengdu, Sichuan, 610400, People’s Republic of China; 2Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 4Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China, Tel +86-10-18908176456, Email chenjian792@163.comPurpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD.Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure.Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07– 1.31, p< 0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06– 1.24, p< 0.001). Compared to the medium group (Q2 ≥ 3.15, < 4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08– 2, p=0.013), and 1.31 (95% CI: 1.06– 1.61, p=0.013) for 90-day mortality in the high group (Q3≥ 4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468– 0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141– 1.509, p< 0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102– 1.386, p< 0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results.Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.Keywords: COPD, serum phosphate, mortality, MIMIC-IV, critically ill

Lixia Li,1,&ast; Xiaohui Huang,1,&ast; Jingxian Liu,2,&ast; Chao Li,1 Zhiyan Lin,1 Rongrong Ren,3 Yan Zhang,3 Haoshu Ding,3 Jihui Chen,1 Yanfei Mao3 1Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanfei Mao; Jihui Chen, Email maoyanfei@xinhuamed.com.cn; chenjihui@xinhuamed.com.cnBackground: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety.Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis.Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L.Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.Keywords: Polymyxin B, PMB therapeutic drug monitoring, TDM, carbapenem-resistant gram-negative bacteria, CR-GNB, clinical efficacy, acute kidney injury, AKI

Yun Han,1,&ast; Jianping Zhu,1,&ast; Jieqiong Liu,2 Ying Zheng,2 Gang Liang,1 Yi Yang,1 Lingyan Yu,3 Zhenwei Yu,1 Gang Han1 1Research Center for Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 3Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenwei Yu; Gang Han, Email yzw_srrsh@zju.edu.cn; 3199022@zju.edu.cnIntroduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets.Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR.Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions.Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.Keywords: ceftazidime, avibactam, pharmacokinetic/pharmacodynamic, probability of target attainment

Jilei Li,1,&ast; Wenchao Dan,2,&ast; Chenchen Zhang,3 Nian Liu,3 Yichong Wang,1 Jixiang Liu,3 Shengsheng Zhang1 1Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengsheng Zhang, Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, Tel +8613801088329, Email zhangshengsheng@bjzhongyi.comPurpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro.Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model.Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2.Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology. Keywords: berberine, ulcerative colitis, TLR4/NF-κB/HIF-1α, network pharmacology, molecular docking, experimental validation, inhibitor

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes

Luxun Yang,1,&ast; Haiying Ran,2,&ast; Yaru Yin,1 Jing Liu,1 Binghui Lu,1 Xi Ran,3 Shenglin Luo,1 Weidong Wang,4 Zhangyou Yang,5 Rong Li1 1Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Biomedical Analysis Center, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Department of Medical Laboratory, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China; 5Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhangyou Yang, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China, Email yangzhangyou@cqmu.edu.cn Rong Li, Army Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China, Tel +86-13883996627, Fax +8623-68753127, Email lrong361@126.comPurpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.Keywords: radioprotective effect, ceria nanoclusters, mitochondria targeting, oxidative stress, superoxide dismutase

Haisong Hou,1,2 Liu Liang,3 Lihong Deng,4 Wanping Ye,5 Yuanzhang Wen,6 Jun Liu1 1Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Department of Hepatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 5Department of Gastroenterology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 6Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jun Liu, Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China, Email liujungd6@163.comBackground: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥ 500 copies/mL were significantly higher in the HCC group than in the controls (all p< 0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥ 60 years (OR: 1.835, 95% CI: 1.020– 3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796– 17.288, p< 0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106– 4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001– 1.007, p=0.002) were risk factors for HCC in patients with CHB.Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.Keywords: chronic hepatitis B, hepatocellular carcinoma, cirrhosis, hepatitis B virus

Wanlan Fu,1 Yunxiang Cao,2 Jian Liu,2 Chuanbing Huang,2 Kaiyan Shu,1 Nanfei Zhu1 1First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, People’s Republic of China; 2Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of ChinaCorrespondence: Yunxiang Cao, Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, Anhui, 230031, People’s Republic of China, Tel +86-13514984395 ; +0551-62838591, Email cyx800805@163.comPurpose: This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis.Methods: Rats were injected with Freund’s complete adjuvant to establish a rat model of AA. Then, some modeled rats were given normal saline or drugs only, and some modeled rats were injected with adeno-associated viruses or necrosulfonamide (NSA; a pyroptosis inhibitor) before drug administration. Toe swelling and arthritis index (AI) were calculated. Pathological and morphological changes in synovial and myocardial tissues were analyzed with hematoxylin-eosin staining, and pyroptotic vesicles and the ultrastructural changes of myocardial tissues were observed with transmission electron microscopy. The serum levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were detected, and lactate dehydrogenase (LDH) release was measured in myocardial tissues, accompanied by the examination of GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD) expression in myocardial tissues.Results: After AA modeling, rats presented with significantly increased toe swelling and AI scores, synovial and myocardial tissue damage, elevated pyroptotic vesicles, and markedly enhanced serum levels of IL-1β, IL-18, IL-6, and TNF-α, accompanied by significantly diminished GAS5 expression, substantially augmented miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression, greatly increased LDH release in myocardial tissues. XFC treatment significantly declined toe swelling, AI scores, synovial and myocardial tissue damage, and the serum levels of IL-1β, IL-18, IL-6, and TNF-α in AA rats. Additionally, XFC treatment markedly elevated GAS5 expression and substantially lowered LDH release and miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression in myocardial tissues of AA rats. Moreover, the above effects of XFC in AA rats were further promoted by GAS5 overexpression or NSA treatment.Conclusion: XFC alleviated myocardial injury in AA rats by regulating the GAS5/miR-21/TLR4 axis and inhibiting pyroptosis and pro-inflammatory cytokine secretion.Keywords: adjuvant arthritis, myocardial injury, GAS5/miR-21/TLR4 axis, pyroptosis, Xinfeng Capsule

Xundi Bao,1 Shuo Liang,1 Jun Li,1 Qian Ye,1 Dandan Wu,1 Shu Wang,2 Yue Li,1 Yunsheng Ding,1 Jie Liu3 1Clinical Laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 2Department of Science and Education, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 3Tuberculosis Control Institute, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xundi Bao, Clinical laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), No. 397, Jixi Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86-13866774716, Email baoxundi@163.comObjective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022.Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted.Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ 2=14.895,76.534,6.032,5.109, all P< 0.05).Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.Keywords: tuberculosis, mycobacterium, drug resistance, surveillance, population distribution, characteristic analysis

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

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

Jing Liu,1,&ast; Tingting Hu,2,3,&ast; Yulan Guan,2,4 Jinguo Zhai2 1Department of Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Gynecology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 4Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510105, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulan Guan, Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, No. 261 Datong Road, Yuexiu District, Guangzhou, 510105, People’s Republic of China, Tel +8615989117143, Email 15989117143@163.com Jinguo Zhai, Nursing School, Southern Medical University, No. 1023-1063 Sha Tai Nan Road, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +8618620287620, Email helenjxzhai@gmail.comPurpose: To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model.Methods: Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated.Results: Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944– 0.978) and 0.902 (95% CI:0.840– 0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively.Conclusion: The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.Keywords: ovarian cancer, incidence factors, decision tree model, risk prediction

Xiaozhi Li,1 Yue Leng,2 Zhiheng Xiong,3 Jing Liu4 1Department of Physical Education, Southeast University, Nanjing, 211189, People’s Republic of China; 2School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, 211189, People’s Republic of China; 3School of Humanities, Southeast University, Nanjing, 211189, People’s Republic of China; 4WuShu Department, Nanjing Sports Institute, Nanjing, 210046, People’s Republic of ChinaCorrespondence: Yue Leng, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, 211189, People’s Republic of China, Email lengyue@seu.edu.cnPurpose: Baduanjin, as a Chinese traditional fitness exercise, can help people regulate emotions and promote their physical and psychological health. However, the underlying neural mechanisms have not been thoroughly explored. This study aimed to examine the effects of differences in the level of Baduanjin learning on individuals’ brain and psychological response related to emotion regulation.Methods: Twenty-two participants with long-term Baduanjin learning (for more than one year), and 21 participants with short-term Baduanjin learning (for approximately three months) were recruited. All participants were asked to do a complete 12-minute set of Baduanjin. Before and after doing Baduanjin, their resting-state EEG signals were collected, besides, the Emotion Regulation Questionnaire (ERQ) and the Profile of Mood States-Short Form (POMS-SF) were used to assess participants’ emotion regulation strategies and abilities.Results: The results of psychological measurement indicated that participants in the long-term group were more likely to use cognitive reappraisal as an emotion regulation strategy compared to participants in the short-term group (p< 0.05). Moreover, the analysis of the frontal alpha asymmetry (FAA) showed that participants in the long-term group rather than the short-term group exhibited significant left lateralization after doing Baduanjin (p< 0.05).Conclusion: The findings provide preliminary evidence for the neural mechanism underlying how long-term Baduanjin learning promotes individuals’ emotion regulation indexed by FAA. The study provides a new paradigm for research on how Baduanjin affects emotional regulation.Keywords: emotion, sport, resting state electroencephalogram, frontal alpha asymmetry

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Jingjing Wang,1 Yirui Dong,1 Xuewei Zheng,1 Haodi Ma,1 Mengjiao Huang,1 Dongliao Fu,1 Jiangbo Liu,2 Qinan Yin1,3 1School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Department of General Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Henan Engineering Research Center of Digital Pathology and Artificial Intelligence Diagnosis, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of ChinaCorrespondence: Qinan Yin, School of Medical Technology and Engineering, Henan University of Science and Technology, No. 263 Kaiyuan Avenue, Luoyang, People’s Republic of China, 471003, Email qinanyin@haust.edu.cn Jiangbo Liu, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Guanlin Avenue, Luoyang, 471031, People’s Republic of China, Email jiangboliuxing@163.comAbstract: Innate immunity is the first line of defense in the human body, and it plays an important role in defending against viral infection. Viruses are identified by different pattern-recognition receptors (PRRs) that activate the mitochondrial antiviral signaling protein (MAVS) or transmembrane protein 173 (STING), which trigger multiple signaling cascades that cause nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) to produce inflammatory factors and interferons (IFNs). PRRs play a pivotal role as the first step in pathogen induction of interferon production. Interferon elicits antiviral activity by inducing the transcription of hundreds of IFN-stimulated genes (ISGs) via the janus kinase (JAK) – signal transducer and activator of transcription (STAT) pathway. An increasing number of studies have shown that environmental, pathogen and host factors regulate the IFN signaling pathway. Here, we summarize the mechanisms of host factor modulation in IFN production via pattern recognition receptors. These regulatory mechanisms maintain interferon levels in a normal state and clear viruses without inducing autoimmune disease.Keywords: pattern recognition receptors, interferon-signaling pathway, host factors

Jingzhan Huang,1,&ast; Jialong Liu,1,&ast; Jin Lan,1,&ast; Jingbo Sun,1 Kun Zhou,1 Yunyao Deng,1 Li Liang,2 Lixin Liu,1,&ast; Xiaolong Liu1 1Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Liu; Xiaolong Liu, Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, Guangdong, 510630, People’s Republic of China, Email llx0129@i.smu.edu.cn; lxl1979@i.smu.edu.cnBackground: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. Keywords: GRSF1, CRC, proliferation, metastasis, Ras/PI3K/Akt

Li-Chao Ma,1,2 Shi-Ning Lou,3 Xiao-Li Zhu,3 Ruo-Lan Zhang,1 Lin Wu,1 Jiang-Yuan Xu,1 Xiao-Juan Ding,1 Juan Liu,4 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, 071000, People’s Republic of China; 2Operating Room, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Traditional Chinese Medicine, Work’s Hospital of China Lucky Group Corporation, Baoding, Hebei, 07100, People’s Republic of China; 4Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of ChinaCorrespondence: Juan Liu, Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, No. 212 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13582292161, Email juanliulj07@126.com Yan Wang, School of Nursing, Hebei University, No. 342 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13833258628, Email ywang_dr06@163.comObjective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population.Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi’s method of descriptive data analysis.Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) “Insufficient CR resources for patients”: Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) “Patient CR initiative”: Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise.Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.Keywords: coronary heart disease, cardiac rehabilitation, community sanitation service, self-care, patient needs

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

Changzhen Li,1,&ast; Xiaomei Wang,1,&ast; Jingjing Rao,1,&ast; Ye Zeng,1 Jianjun Liu,2 Feng Tang1 1Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China; 2Office of the Dean, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Tang; Jianjun Liu, Email tang33feng66@163.com; liujianjun5221@163.comObjective: To analyze bacterial distribution and antibiotic resistance in clinical specimens from a Chinese hospital for evaluating environmental factors’ impact on pathogen prevalence.Methods: From January 2017 to December 2021, we collected 42,854 clinical specimens from hospitalized children and women. The specimens were cultured on various agar plates and incubated at 35°C for 18– 48 h. Their identification was performed using standard biochemical methods and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF), whereas antibiotic susceptibilities were determined using the VITEK 2 system. Concurrent environmental data from Wuhan were analyzed for correlations with pathogen prevalence using multiple linear stepwise regression.Results: Of the 24,555 bacterial strains isolated, the majority were gram-positive, and sputum was the most common specimen type. Haemophilus influenzae and Escherichia coli were the most prevalent pathogens in sputum and urine samples, respectively. Notably, H. influenzae and Streptococcus pneumoniae affected children under 6 years of age the most. Furthermore, H. influenzae showed high ampicillin resistance but low cefotaxime resistance; S. pneumoniae was sensitive to penicillin G, and E. coli was resistant to ampicillin but sensitive to cefotetan. The prevalence of multidrug-resistant organisms was below national averages. In terms of seasonality, H. influenzae peaked during late winter and early spring, and environmental analysis indicated positive correlations between PM2.5 and PM10, and H. influenzae and S. pneumoniae prevalence. In addition, NO2 levels were positively correlated with increased S. aureus and M. catarrhalis prevalence; E coli prevalence was negatively correlated with ozone levels.Conclusion: This study provides valuable insights into the distribution and antibiotic resistance patterns of bacterial pathogens in maternal and child healthcare facilities in Wuhan, China. Environmental factors significantly influence the epidemiology of certain bacterial pathogens. Implementing integrated health strategies that combine microbial surveillance with environmental monitoring is needed to effectively manage and prevent bacterial infections.Keywords: epidemiology, multidrug-resistant pathogens, seasonality, particulate matter

Yan Ji,1 Haorong Li,1 Jiguo Li,2 Guangqiang Yang,1 Wenli Zhang,1 Yan Shen,1 Bohui Xu,3 Jianping Liu,1 Jingyuan Wen,4 Wenting Song1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Nanjing Miaobang Meiye Enterprise Management Co, LTD, Nanjing, People’s Republic of China; 3School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 4School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New ZealandCorrespondence: Wenting Song, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Email songwenting908@163.com Jingyuan Wen, School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand, Email j.wen@auckland.ac.nzPurpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris.Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo.Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy.Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.Keywords: acne vulgaris, azelaic acid, hair follicle, micro/nanocrystals, targeted delivery

Jing Liu,1,&ast; Zeyi Liang,1,&ast; Maocao Zhongla,2 Hongsheng Wang,3 Xu Sun,4 Juanshan Zheng,1 Xuezhi Ding,1 Feng Yang1 1Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, People’s Republic of China; 2Gannan Animal Disease Prevention and Control Center, Hezuo, People’s Republic of China; 3Xiangyang Vocational and Technical College, Xiangyang, People’s Republic of China; 4College of Life Sciences and Engineering, Lanzhou University of Technology, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of enterococcal isolates (Enterococcus faecalis, Enterococcus faecium and Enterococcus hirae) isolated from clinical bovine mastitis cases in Ningxia, China.Patients and Methods: The enterococci were identified by 16S rRNA amplification and sequencing. Antimicrobial resistance was determined by disc diffusion method. Virulence and antimicrobial resistance genes were detected by PCR assays.Results: Overall, 198 enterococcal isolates were identified from 2897 mastitis samples, including 137 (4.7%) E. faecalis, 50 (1.7%) E. faecium and 11 (0.4%) E. hirae. E. faecalis, E. faecium and E. hirae isolates showed high resistance to tetracycline (92.7%, 68.0%, 90.9%), followed by erythromycin (86.9%, 76.0%, 72.7%). The multidrug-resistant strains of E. faecalis and E. faecium were 29 (21.2%) and 13 (26.0%), respectively. The resistance of E. faecalis, E. faecium and E. hirae isolates to tetracycline is mainly attributed to the presence of tetL (alone or combined with tetM and/or tetK), the erythromycin resistance to ermB (alone or combined with ermC and/or ermA). Moreover, cpd (94.2%), gelE (77.4%), efaAfs (93.4%), and esp (79.6%) were the most common virulence genes in E. faecalis. In E. faecium, except for the gene efaAfs (82.0%), other virulence genes are rarely found. Only two strains of E. hirae carrying asa1 gene were detected.Conclusion: The results of this study can provide a reference for the prevention and treatment of bovine mastitis caused by enterococci.Keywords: bovine mastitis, enterococci, antimicrobial resistance, virulence

Jie Liu,1,2,&ast; Yongkai Wang,3,&ast; Zhihui Jiang,4,&ast; Guangqi Duan,1 Xiaowen Mao,5 Danping Zeng2 1Department of Pediatric Surgery, Yijishan Hospital of Wannan Medical College, Wannan Medical College, Wuhu, People’s Republic of China; 2Department of General Surgery and Urology, Maternal and Child Health Hospital/Obstetrics and Gynecology Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 3Department of Hepatobiliary Surgery, Yijishan Hospital of Wannan Medical College, Wannan Medical College, Wuhu, People’s Republic of China; 4Department of General Surgery, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China; 5Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danping Zeng, Department of General surgery and urology, Maternal and Child Health Hospital/Obstetrics and Gynecology Hospital of Guangxi Zhuang Autonomous Region, No. 225, Xinyang Road, Nanning City, Guangxi Zhuang Autonomous Region, 530003, People’s Republic of China, Email zengdp000@icloud.com Xiaowen Mao, Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, 746 Wuluo Road, Hongshan District, Wuhan City, Hubei Province, 430070, People’s Republic of China, Email xiaowenmao0927@163.comPurpose: The objective of this study was to develop and validate a nomogram for predicting the need for surgical intervention in pediatric intussusception after pneumatic reduction.Patients and Methods: This retrospective study analyzed the clinical data of children with acute intussusception admitted to four hospitals in China from January 2019 to January 2022. Based on the results of pneumatic reduction, the patients were divided into two groups: the successful reduction group (control group) and the failed reduction group (operation group). The total sample was randomly divided into a training set and a validation set in a 7:3 ratio. Logistic regression analysis was performed to establish a predictive model for surgical risk.Results: A total of 1041 samples were included in this study, with 852 in the control group and 189 in the operation group. Among the total sample, 728 cases were used for training and 313 cases were used for validation. Logistic regression analysis of the training set identified age, time of abdominal pain, presence or absence of hematostoecia, C-reactive protein value from blood test on admission, and nested position indicated by B-ultrasound as independent predictors of intussusception intervention. Based on the five independent risk factors identified through multivariate logistic regression, a nomogram was successfully constructed to predict the failure of resetting by air enema under X-ray.Conclusion: A nomogram was developed to predict the need for surgical intervention after intussusception pneumatic reduction in children. The nomogram was based on clinical risk factors including age, time of abdominal pain, presence or absence of blood in stool, value of C-reactive protein in blood test on admission, and nested position indicated by B-ultrasound. Our internal validation demonstrated that this nomogram can serve as a useful tool for identifying risk factors associated with failure of air enema in children with intussusception.Keywords: pediatric, intussusception, pneumatic reduction, nomogram, surgical intervention

Wan-Qiong Zhou,1,&ast; Yi-Tian Gao,1,&ast; Ying Wang,2,&ast; Jing Liu,1 Qiu-Yi Wang,1 Lan-Shu Zhou1 1School of Nursing, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nursing, The First Rehabilitation Hospital of Shanghai, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan-Shu Zhou, School of Nursing, Naval Medical University, 800 Xiangyin Road, Shanghai, People’s Republic of China, Tel +86-13761801446, Email zhoulanshu@hotmail.comPurpose: To conducted a scoping review of care needs of older adults with disabilities at home and in the community and provide a comprehensive understanding of the essential needs of older adults with disabilities.Methods: Eight databases were searched for relevant Chinese and English studies (supplemented by retrospective references of the included studies) from the establishment of the database to February 13, 2023. An thematic synthesis approach was used to qualitatively integrate the retrieved studies and identify need-related themes.Results: A total of 6239 studies were retrieved, 2557 were de-weighted and excluded, and 56 were obtained after the double screening. Studies were from 11 countries. Thirty-three studies used a self-prepared survey instrument to investigate needs, and the other research tools commonly used were secondary databases and the Long-Term Care Needs of the Disabled Scale. A total of 78 specific need items were identified and summarized into three need themes based on the ICF framework: physical functioning needs, activity and participation needs, and environment needs.Conclusion: The complex physical and mental health conditions faced by older adults with disabilities result in multifaceted, integrated needs that are difficult to identify and meet. Current research on older adults with disabilities is limited to common care. Future research should focus on the specificities of the older disabled population and understand the diverse care needs of people with disabilities in order to better target care services for this group. Policymakers should formulate more operational and strategic measures based on the actual needs of older adults with disabilities to expand the coverage of services and to pinpoint care services.Keywords: disability, elderly, diverse care, scoping review

JiuLing Deng,1,&ast; Jing Liu,1,&ast; WanSheng Chen,2,3,&ast; Qing Liang,1 YuQiong He,2,3 GuangChun Sun1 1Department of Pharmacy, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China; 2Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: GuangChun Sun, Department of Pharmacy, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, 200240, People’s Republic of China, Tel +86 21 24289464, Email sunguangchun@5thhospital.com YuQiong He, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Tel +86 21 81886182, Email yuqionghe1993@163.comAbstract: With ever-increasing intensive studies of idiopathic pulmonary fibrosis (IPF), significant progresses have been made. Endoplasmic reticulum stress (ERS)/unfolded protein reaction (UPR) is associated with the development and progression of IPF, and targeting ERS/UPR may be beneficial in the treatment of IPF. Natural product is a tremendous source of new drug discovery, and accumulating studies have reported that many natural products show potential therapeutic effects for IPF via modulating one or more branches of the ERS signaling pathway. Therefore, this review focuses on critical roles of ERS in IPF development, and summarizes herbal preparations and bioactive compounds which protect against IPF through regulating ERS.Keywords: idiopathic pulmonary fibrosis, endoplasmic reticulum stress, natural products, mechanisms

Fuyu Zhao,1– 3,&ast; Jianan Zhao,1– 3,&ast; Kai Wei,1– 3 Ping Jiang,1– 3 Yiming Shi,1– 3 Cen Chang,1– 3 Yixin Zheng,1– 3 Yu Shan,1– 3 Yunshen Li,1– 3 Bingheng He,4 Mi Zhou,1,3 Jia Liu,1,3 Li Li,1,3 Shicheng Guo,1 Dongyi He1– 3 1Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Rehabilitation, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongyi He, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email dongyihe@medmail.com.cnAbstract: Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2), apoptosis (Interferon Alpha Inducible Protein 6, G1P3), differentiation (Grainyhead Like Transcription Factor 2, GRHL2), and angiogenesis (Vascular Endothelial Growth Factor, VEGF); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α; Interleukin-17, IL-17); and signaling pathways (JAK-STAT, Nuclear Factor Kappa B, NF-κB) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.Keywords: psoriasis, siRNA, keratinocytes, targeted delivery

Yongxiong Huang,1,2,&ast; Xianshuai Qiu,3,&ast; Jinlian Liu,4 Jiangtao Wan,5 Cheng Yu,1 Chun Liu,1 Yang Duan,1 Chong Chen,2 Jingxing Dai,6 Jun Ouyang,6 Ming Liu,3 Shaoxiong Min,1,5 Sujun Qiu1 1Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Spine Surgery, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, 510000, People’s Republic of China; 3Department of Orthopedics and Sports Medicine Center, Heyou Hospital, Foshan, 528333, People’s Republic of China; 4Department of Pathophysiology, Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 5Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Medical Biomechanics & National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sujun Qiu, Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China, Email qiusjspine@126.com Shaoxiong Min, Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email msxbear24@163.comBackground: Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD.Methods: Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples.Results: We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group.Conclusion: We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD. Keywords: intervertebral disc degeneration, mitophagy-related differentially expressed genes, immune infiltration, diagnostic model, SQSTM1, nucleus pulposus cells

Jie Liu, Lijuan Lu, Yu Wei, Yu Li, Qiong Wang, Lei Yu, Langen Zhuang, Guoxi Jin, Xiaoyan Pei Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province, People’s Republic of ChinaCorrespondence: Guoxi Jin; Xiaoyan Pei, Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, Anhui Province, 233000, People’s Republic of China, Email jyzjyz1999@163.com; 245899985@qq.comAbstract: Pseudohypoparathyroidism (PHP) is a rare genetic disease characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) in serum. Here, we report a case of a patient with pseudohypoparathyroidism type IB (PHPIB) and subclinical hypothyroidism, analyze the clinical and genetic data of his family members, review the relevant literature, and classify and discuss the pathogenesis and clinical characteristics of each subtype. Finally, we discuss the treatment approach to improve clinicians’ understanding of the disease.Keywords: hypocalcemia, parathyroid hormone resistance, GNAS, STX16, molecular genetic mechanism

Xiping Liao,1,2,&ast; Ji Liu,3,&ast; Xiaolong Guo,1 Ruiping Meng,1 Wei Zhang,1 Jianyun Zhou,1 Xia Xie,1,2 Hongli Zhou1 1Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Xie, Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email xiexia0128@163.com Hongli Zhou, Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email zhouhli7@mail2.sysu.edu.cnAbstract: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (M&phis;s) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease’s progression. On the other hand, their differentiated offsprings, namely moM&phis;s and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes’ origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD’s course. Through this lens, we aspire to furnish novel perspectives into IBD’s etiology and potential therapeutic strategies.Keywords: IBD, monocytes, inflammatory response

Juanjuan Liu,1 Minqin Xu,1 Ling Zhou,1 Li Yang,1 Hong Li,2 Xue Li1 1Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Xue Li, Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 1055 San Xiang Road, Suzhou, 215004, People’s Republic of China, Tel +8613584834618, Email zlanling@163.comObjective: To investigate the magnetic resonance imaging (MRI) features of women with prior second-trimester pregnancy loss, and to establish a nomogram prediction model for subsequent miscarriage.Methods: A retrospective cohort study of women with prior second-trimester pregnancy loss from January 2018 to December 2021 in Second Affiliated Hospital of Soochow University was performed. A total of 245 patients were included. Data from January 2018 to December 2019 were used to construct the model, and data from January 2020 to December 2021 were used to evaluate the model. Data on maternal demographic characteristics, MRI cervical measurements were extracted. The prediction model was constructed with independent variables determined by multivariate logistic regression analyses. Through receiver-operating characteristic (ROC) curve analysis, the predictive ability of the model for subsequent second trimester pregnancy loss in women was evaluated, and internal validation was performed through validation data.Results: Thin cervix was observed in 77 (31.42%) women with prior second-trimester pregnancy loss, the mean longitudinal diameter of cervical canal on MRI was 11.76± 2.75mm. The model reached a sensitivity of 80%, specificity of 75.90%, positive predictive value (PPV) of 55.80% and negative predictive value of 90.90%; ROC characteristics proved that the model was superior to any single parameter with an AUC of 0.826.Conclusion: Our observations showed that thin cervix and longitudinal diameter of cervical canal reliably predicted second trimester pregnancy loss. We developed and validated a nomogram model to predict the individual probability of second trimester pregnancy loss in the next pregnancy and hopefully improve the prediction and indication of interventions.Keywords: cervical insufficiency, MRI, nomogram, magnetic resonance imaging, CI

Guo Chen,1 Duoduo Yu,2 Yichen Wang,1 Zou Ma,1 Mengna Bi,1 Lisha Lu,1 Shangshang Zhang,1 Jiaxin Liu,1 Hu Chen,1 Hai Shen,2 Huiwu Zhang,2 Xiaobing Luo,2 Yan Si,1 Peng Zhang1 1Department of Geriatric Orthopedics(1), Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan, 610041, People’s Republic of China; 2Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Peng Zhang, Tel +86-19980487275, Email yicoal@yeah.netPurpose: The aim of this study is to investigate the effects of a preoperative combined with postoperative moderate-intensity progressive resistance training (PRT) of the operative side in patients with hip osteoarthritis (HOA) who are undergoing total hip arthroplasty (THA). The study seeks to evaluate the impact of this combined intervention on muscle strength, gait, balance, and hip joint function in a controlled, measurable, and objective manner. Additionally, the study aims to compare the outcomes of this combined intervention with those of preoperative or postoperative muscle strength training conducted in isolation.Methods: A total of 90 patients with HOA scheduled for unilateral primary THA were randomly assigned to three groups: Pre group (preoperative PRT), Post group (postoperative PRT), and Pre& Post group (preoperative combined with postoperative PRT) focusing on hip flexion, extension, adduction, and abduction of operated side. Muscle strength, gait parameters, balance, and hip function were assessed at specific time points during a 12-month follow-up period.Results: All three groups showed significant improvements in muscle strength, with the Pre& Post group demonstrating the most pronounced and sustained gains. Gait velocity and cadence were significantly improved in the Pre& Post group at 1-month and 3-month postoperative follow-ups compared to the other groups. Similarly, the Pre& Post group exhibited superior balance performance at 3-month and 12-month postoperative follow-ups. The Harris Hip Score also showed better outcomes in the Pre& Post group at all follow-up intervals.Conclusion: Preoperative combined with postoperative moderate-intensity PRT in HOA patients undergoing THA led to superior improvements in muscle strength, gait, balance, and hip joint function compared to preoperative or postoperative PRT alone. This intervention shows significant promise in optimizing postoperative rehabilitation and enhancing patient outcomes following THA.Keywords: exercise therapy, muscle strength, progressive resistance training, total hip arthroplasty, gait variability

Wei Zheng, Jianhua Liu, Haixia Bai, Xin Xu, Lina Wu, Xiaosong Qin Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shengyang, People’s Republic of ChinaCorrespondence: Xiaosong Qin, Email qinxs@sj-hospital.orgBackground: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea.Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization–time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime.Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.Keywords: spontaneous bacterial peritonitis, rare pathogen, Gordonia terrae, identification

Wanying Wu,1,2,&ast; Congzhuo Jia,1,2,&ast; Xiayan Xu,1– 3 Yibo He,1,2 Yun Xie,1,2,4 Yang Zhou,1,2 Hongyu Lu,1,2 Jin Liu,1,2 Jiyan Chen,1,2 Yong Liu1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyan Chen; Yong Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.com; liuyong@gdph.org.cnBackground: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status.Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality.Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06– 1.18; HR 1.21, 95% CI 1.14– 1.29; HR 1.43, 95% CI 1.34– 1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08– 1.30; HR 1.58, 95% CI 1.44– 1.74; HR 1.89, 95% CI 1.72– 2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P < 0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity > 0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets.Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group.Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.Keywords: platelet-to-HDL-cholesterol ratio, coronary artery disease, diabetes, all-cause mortality, cardiovascular mortality

Dongmei Zou,1,&ast; Yanqiong Liu,2,&ast; Youwen Gong,3 Xueqing Zhang,4 Jieqiong Liu,4 Jinhua Shen4 1Department of Cardiovascular Surgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde city), Changde, People’s Republic of China; 2Department of Cardiology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 3Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 4Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youwen Gong, Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 1755144149@qq.com Xueqing Zhang, Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 382731326@qq.comPurpose: This study investigated the current state of self-efficacy and the association between self-perceived burden (SPB) and health-related quality of life (HRQoL) among Chinese older-adult inpatients.Methods: A cross-sectional study was conducted using convenience sampling to survey Chinese older-adult inpatients. Data regarding demographic characteristics, self-efficacy, SPB, and HRQoL were collected. Pearson’s correlation analysis was used to examine the correlations among the research variables. SPSS® Statistics V26.0, and SPSS® PROCESS Macro Model 4 were used to analyze the available data. The bootstrap method was used to analyze the mediating role of self-efficacy.Results: Survey participants included 514 older-adult inpatients, with a mean age of 72.28± 5.58 years. Self-efficacy (r=0.471, p< 0.01) was positively correlated with HRQoL, whereas self-efficacy (r=− 0.891, p< 0.01) and HRQoL (r=− 0.516, p< 0.01) were negatively correlated with SPB. The mediating effect analysis revealed that self-efficacy either completely or partially mediated the effect of SPB on HRQoL, with the indirect effect accounting for 30.2% of the total.Conclusion: This study provides a mediating model suggesting that SPB exerts both direct and indirect effects on the HRQoL of older-adult inpatients through self-efficacy.Keywords: aging, Chinese, negative emotions, self-efficacy, health-related quality of life, mediating effects

Lihua Zhou,1,&ast; Kun Zhang,2,3,&ast; Juanjuan Guo,4 Jianbo Liu,5 Suhong Wang,6 Jingbo Gong7 1College of Education Science, Hengyang Normal University, Hengyang, People’s Republic of China; 2Suzhou Guangji Hospital, Suzhou, People’s Republic of China; 3Affiliated Guangji Hospital of Soochow University, Suzhou, People’s Republic of China; 4School of Education, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 5Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, School of Mental Health, Shenzhen University, Shenzhen, People’s Republic of China; 6Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China; 7Shanghai Changning Mental Health Centre, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingbo Gong, Shanghai Changning Mental Health Center, Shanghai, 200335, People’s Republic of China, Email yefenhua@126.com Suhong Wang, Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China, Email yarmine@gmail.comBackground: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences.Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction.Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females.Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.Keywords: perceived stress, impulsivity, executive dysfunction, non-suicidal self-injury, gender difference

Jie Liu,1,&ast; Xiajie Huang,1,&ast; Hongjie Su,1 Jie Yu,1 Xinyu Nie,1 Kaibing Liu,1 Wencong Qin,1 Yongxin Zhao,1 Yongfeng Su,1 Xiaocong Kuang,2 Di Chen,3 William W Lu,4 Yan Chen,1 Qikai Hua1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Yulin Campus of Guangxi Medical University, Yulin, Guangxi, People’s Republic of China; 3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 4Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Qikai Hua, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email cy003@connect.hku.hk; hqk100@yeah.netPurpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration.Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA.Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001).Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.Keywords: distraction osteogenesis, tibial cortex transverse transport, diabetic foot, HIF-1α, angiogenesis

Zhangrui Zeng,1,&ast; Yueshuai Wei,1,&ast; Caihong Ye,1 Yuan Jiang,1 Chunlin Feng,1 Tongtong Guo,1 Min Song,1 Yinhuan Ding,1 Ping Zhan,2 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 2Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China, Te/Fax +86 0830 3165730, Email liujb7203@swmu.edu.cnPurpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections.Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections.Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors.Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.Keywords: carbapenem-resistant, Enterobacter cloacae complex, antimicrobial resistance, molecular characteristics, risk factors

Ling Shi,1 Yunjun Zhou,2 Yongkui Yin,1 Jin Zhang,3 Kaiyuan Chen,1 Sen Liu,1 Peijian Chen,1 Hua Jiang,2 Jieting Liu,1 Yan Wu1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, 157000, People’s Republic of China; 2The Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, 157000, People’s Republic of China; 3Clinical Laboratory, Zhejiang Medical & Health Group Quzhou Hospital, Quzhou, 324004, People’s Republic of ChinaCorrespondence: Yan Wu; Jieting Liu, College of Life Science, Mudanjiang Medical University, 3 Tong Xiang Street, Ai Min District, Mudanjiang, 157000, People’s Republic of China, Tel +86-0453-6984647, Email wuyan@mdjmu.edu.cn; ttiebj1@163.comAbstract: Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.Keywords: exosomes, biomaterials, hydrogels, geriatric diseases, injury repair

Shengchao Hou,1,2 Xiubo Wang,1 Zizhao Zhao,1 Yongqiang Ma,1 Jing Liu,3 Ziyun Zhang,2 Jingdong Ma1 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Administrative Office, Yuebei People’s Hospital, Shaoguan, People’s Republic of ChinaCorrespondence: Jingdong Ma, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, People’s Republic of China, Email jdma@hust.edu.cnPurpose: Advancements in electronic health (eHealth) technology have profoundly impacted patient engagement. This study aimed to develop and validate the Electronic Patient Engagement Behavior (EPEB) scale to measure the conceptual and underlying framework of patient engagement behaviors in an eHealth context.Patients and Methods: Initial measurement items were generated based on a literature review and qualitative research. Two rounds of surveys, a pilot survey and validation survey, were conducted to evaluate the psychometric properties of the scale.Results: The EPEB scale consists of 15 items in four dimensions: disease information search, physician-patient interaction, social interaction between patients, and disease self-monitoring. In the pilot survey, the exploratory factor analysis revealed a four-factor model, explaining 69.411% of variance. In the validation survey, the Cronbach’s α coefficient of each sub-scale was 0.865, 0.904, 0.904, and 0.900 respectively. The Spearman-Brown split coefficient of the scale was 0.963. The results of the cross-sex measurement equivalence test indicate that all fit indices met the measurement criteria. The confirmatory factor analysis indicated second-order 4-factor model fit the data well. The EPEB has a good reliability and validity.Conclusion: The EPEB scale provides a reliable tool for measuring patient engagement behaviors in the eHealth context. The utilization of this scale may yield valuable insights into strategies for enhancing patient engagement and optimizing health outcomes.Keywords: patient engagement behaviors, electronic health, scale development, evaluation, validation

Lve Cheng,&ast; Junwei Niu,&ast; Yao Cheng,&ast; Jie Liu, Mengjia Shi, Shijia Huang, Xiong Ding, Shengwei Li Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Ding; Shengwei Li, Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong, Chongqing, 400010, People’s Republic of China, Tel +86-13677662766 ; +86-13508312245, Email dingxiong@hospital.cqmu.edu.cn; lishengwei@hospital.cqmu.edu.cnBackground: There is a lack of validated predictive models for the occurrence of systemic inflammatory response syndrome (SIRS) after percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) for the treatment of hepatolithiasis. This is the first study to estimate the incidence of SIRS after PTCSL.Methods: A retrospective analysis of 284 PTCSL sessions for the treatment of hepatolithiasis at our institution between January 2019 and January 2023 was performed. The development of SIRS after PTCSL was the primary study endpoint. Independent risk factors for SIRS after PTCSL were identified using univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed using these independent risk factors, and the predictive value was assessed using receiver operating characteristic (ROC) curves.Results: The incidence of SIRS after PTCSL was 20.77%. According to multivariate analysis, the number of PTCSL sessions (odds ratio [OR]=0.399, 95% confidence interval [CI]=0.202– 0.786, p=0.008), stone location (OR=2.194, 95% CI=1.107– 4.347, p=0.024), intraoperative use of norepinephrine (OR=0.301, 95% CI=0.131– 0.689, p=0.004), intraoperative puncture (OR=3.476, 95% CI=1.749– 6.906, P< 0.001), preoperative gamma-glutamyltransferase (OR=1.002, 95% CI=1.001– 1.004, p=0.009), and preoperative total lymphocyte count (OR=1.820, 95% CI=1.110– 2.985, p=0.018) were found to be independent risk factors for the development of SIRS after PTCSL. These six independent risk factors were used to construct a nomogram prediction model, which showed satisfactory accuracy with an area under the ROC curve of 0.776 (95% CI: 0.702– 0.850).Conclusion: The number of PTCSL sessions, stone location, intraoperative use of norepinephrine, intraoperative puncture, preoperative gamma-glutamyltransferase, and preoperative total lymphocyte count may predict the occurrence of SIRS after PTCSL. This prediction model may help clinicians identify high-risk patients in advance.Keywords: percutaneous transhepatic cholangioscopic lithotripsy, hepatolithiasis, systemic inflammatory response syndrome, risk factors, nomogram

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

Yuanfeng Wang,1,&ast; Xu Qiu,1,&ast; Jiao Liu,1,&ast; Xuanyi Liu,1 Jialu Pan,2 Jiayi Cai,2 Xiaodong Liu,1,3 Shugen Qu1,3 1College of Public Health and Management, Zhejiang Provincial Key Laboratory of Watershed Science and Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2The First Clinical Medical College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this work.These authors contributed equally to this workCorrespondence: Xiaodong Liu; Shugen Qu, Email forget45@wmu.edu.cn; shugenju@wmu.edu.cnIntroduction: Sepsis is a worldwide epidemic, with high morbidity and mortality. Cuproptosis is a form of cell death that is associated with a wide range of diseases. This study aimed to explore genes associated with cuproptosis in sepsis, construct predictive models and screen for potential targets.Methods: The LASSO algorithm and SVM-RFE model has been analysed the expression of cuproptosis-related genes in sepsis and immune infiltration characteristics and identified the marker genes under a diagnostic model. Gene-drug networks, mRNA-miRNA networks and PPI networks were constructed to screen for potential biological targets. The expression of marker genes was validated based on the GSE57065 dataset. Consensus clustering method was used to classify sepsis samples.Results: We found 381 genes associated with the development of sepsis and discovered significantly differentially expressed cuproptosis-related genes of 16 cell types in sepsis and immune infiltration with CD8/CD4 T cells being lower. NFE2L2, NLRP3, SLC31A1, DLD, DLAT, PDHB, MTF1, CDKN2A and DLST were identified as marker genes by the LASSO algorithm and the SVM-RFE model. AUC > 0.9 was constructed for PDHB and MTF1 alone respectively. The validation group data for PDHB (P=0.00099) and MTF1 (P=7.2e-14) were statistically significant. Consistent clustering analysis confirmed two subtypes. The C1 subtype may be more relevant to cellular metabolism and the C2 subtype has some relevance to immune molecules.The results of animal experiments showed that the gene expression was consistent with the bioinformatics analysis.Discussion: Our study systematically explored the relationship between sepsis and cuproptosis and constructed a diagnostic model. And, several cuproptosis-related genes may interfere with the progression of sepsis through immune cell infiltration.Keywords: machine learning, cuproptosis, immune infiltration, sepsis, diagnostic model

Guanshuai Guo,1,2,&ast; Xi Chen,1,2,&ast; Jingran Zhang,1,2 Xiangmin Meng,3 Aifeng Jia,4 Xinli Xing,5 Fenglei Huang,6 Xumei Zhang,2,7 Juan Liu,8 Shuying Li,3,9 Qiang Zhang1,2 1Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 4Department of Obstetrics and Gynecology, Tianjin Xiqing Hospital, Tianjin, People’s Republic of China; 5Department of Obstetrics and Gynecology, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 6Department of Reproductive Health, Women’s and Children’s Health Center of Dongchangfu District, Liaocheng, People’s Republic of China; 7Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 8Department of Biomedical Information and Library, Tianjin Medical University, Tianjin, People’s Republic of China; 9NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuying Li, Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, 300380, People’s Republic of China, Email lsy_tj2006@163.com Qiang Zhang, Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Tel +86 022 83336633, Email qiangzhang@tmu.edu.cnPurpose: This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B12.Methods: A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China. Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B12, and homocysteine (Hcy) levels were measured. The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM.Results: N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates. Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B12 levels. However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL. Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B12 are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B12 (RERI: 2.54; 95% CI: 0.17, 4.92).Conclusion: SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B12 levels can modify their associations.Keywords: N6AMT1, folate, vitamin B12, gene-nutrition interaction, gestational diabetes mellitus

Xue Fang Li,1 Shi Rong Liu,2 Jin Jin Li,1 Ning Liu,2 Hui Min Li,3 An Ning Ge,4 Liang Liang Wang,5 Xie Min Dong,1 Hui Wang,1 Ju Liu,1 Lin Zhang,1 Hao Dong Zhang,1 Wei Gou1 1Department of Metabolic Liver Disease, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of China; 2Infectious Diseases department, People’s Hospital of Qu fu City, Qufu City, Shandong Province, People’s Republic of China; 3Infection Department, Jiaozhou Branch of Shanghai East Hospital Tongji University, Qingdao City, Shandong Province, People’s Republic of China; 4Department of Infectious Diseases, People’s Hospital of Rizhao City, Rizhao City, Shandong Province, People’s Republic of China; 5Medical Intervention Department, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of ChinaCorrespondence: Wei Gou, Department of Metabolic Liver Disease, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of China, Tel +86-15666687727, Fax +86-532-81636699, Email gouwei@qdu.edu.cnObjective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis.Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People’s Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35– 77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG < 16 mmHg) and Group B (HVPG ≥ 16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis.Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05).Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.Keywords: portal hypertension, white blood cells, glycine cholate, serum hyaluronic acid

Juan Liu,1,&ast; Min Zhang,2,&ast; Jiandi Huang,1,&ast; Changwei Guo,1 Jie Yang,1 Chengsong Yue,1 Wenjie Zi,1 Qingwu Yang1 1Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 2Department of Neurology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingwu Yang; Wenjie Zi, Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China, Email yangqwmlys@163.com; ziwenjie@126.comPurpose: Acute ischemic stroke (AIS) stands as the primary cause of mortality and extended disability globally. While prior studies have examined the connection between stroke and local weather, they have produced conflicting results. Our goal was to examine the correlation between temperature and functional prognosis in patients with large vessel occlusion (LVO) undergoing endovascular therapy (EVT).Patients and methods: This study included a total of 1809 patients. Temperatures from stroke onset to groin puncture were categorized into Cold (10th percentile of temperature), Cool (10th– 50th percentile of temperature), Warm (50th– 90th percentile of temperature), and Hot (90th percentile of temperature) groups. The primary efficacy result was the modified Rankin Scale (mRS) score at 90 days. Safety outcomes included mortality, symptomatic intracranial hemorrhage (sICH) and complications after cerebral infarction.Results: The primary efficacy results demonstrated a statistical enhancement in functional outcomes at 90 days for patients in the Warm group compared to the Cold group (adjusted common odds ratio [OR]: 1.386; 95% confidence interval [CI]: 1.024– 1.878, P=0.035). Secondary efficacy results showed that temperature was associated with a higher rate of 90-day functional independence (adjusted OR: 1.016; 95% CI: 1.004– 1.029; P=0.009), which was higher in the Warm group compared with patients in the Cold group (adjusted OR: 1.646; 95% CI: 1.107– 2.448, P=0.014). There were no significant differences between groups in terms of sICH, 90-day mortality, and post-infarction complications.Conclusion: Compared with Cold temperature, Warm temperature is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.Keywords: acute ischemic stroke, ambient temperature, large-vessel occlusion, endovascular treatment

Lu Hou,1,&ast; Jing Zhang,2,&ast; Jing Liu,3 Chang Chen,1 Xuezheng Gao,4 Limin Chen,4 Zhenhe Zhou,1,3 Hongliang Zhou5 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China; 2Department of Psychiatry, Huaian Third People’s Hospital, Huaian City, 223021, People’s Republic of China; 3School of Humanities and Management Science, Wannan Medical College, Wuhu City, 241000, People’s Republic of China; 4Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, 214151, People’s Republic of China; 5Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, 214151, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhe Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, 214151, People’s Republic of China, Tel +86-1-335-811-8986, Fax +86-510-83219366, Email zhouzh@njmu.edu.cn Hongliang Zhou, Department of Psychology, the Affiliated Hospital of Jiangnan University, Wuxi City, 214151, People’s Republic of China, Tel +86-1-536-525-1126, Fax +86-510-85808820, Email Hongliangzh2022@hotmail.comPurpose: Nicotine withdrawal is a multifaceted physiological and psychological process that can induce a spectrum of mood disturbances. Gaining a more nuanced understanding of how pure nicotine withdrawal influences cognitive control functions may provide valuable insights for the enhancement of smoking cessation programs. This study investigated changes in inhibitory control function in smokers after 2-hour nicotine withdrawal using the event-related potential (ERP) technique.Participants and Methods: 28 nicotine dependence (ND) patients and 28 health controls (HCs) completed a smoking-cued Go/No-go task containing two different types of picture stimuli, smoking-cued and neutral picture stimuli. We analyzed the behavioral and ERP data using a mixed model Repeated Measure Analysis of Variance (ANOVA).Results: No-go trials accuracy rate (ACC) at baseline (time 1) was lower in the ND group compared to HCs with smoking-cued stimuli, and No-go trials ACC after 2-hour nicotine withdrawal (time 2) was not lower in the ND group compared to HCs. When confronted with smoking-cued stimuli, the No-go trials ACC was higher in time 2 than in time 1 in the ND group. For the ERP component, the No-go N2 amplitudes in the ND group with smoking-cued stimuli were lower than that of HCs, whereas after 2-hour nicotine withdrawal, the ND group’s No-go N2 amplitudes higher than that at time 1, and did not differ from that of HCs. No-go P3 amplitudes were not significantly different between the two groups.Conclusion: Evidenced from ERP data, ND patients have an inhibitory control dysfunction in the face of smoking cues, which is mainly manifested in the early stage of response inhibition rather than in the late stage. Two-hour nicotine withdrawal improves inhibitory control dysfunction in ND patients. The No-go N2 component is an important and sensitive neuroelectrophysiological indicator of inhibitory control function in ND patients.Keywords: nicotine dependence, inhibitory control, 2-hour nicotine withdrawal, event-related potentials, Go/No-go task