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Yang Fang, Xiuying Jin, Huiying Cui, Zhezhu Han, Qiang Xu, Songnan Zhang Department of Oncology, Yanbian University Hospital, Yanji, People’s Republic of ChinaCorrespondence: Songnan Zhang, Email zhangsn21@163.comBackground: Primary hepatic Neuroendocrine carcinoma (PHNEC) is exceptionally rare, and when it cannot be surgically removed locally, systemic combination therapy is the preferred treatment. However, current treatments have shown limited effectiveness, and more effective approach remains a matter of debate.Case Presentation: We present a case involving a female patient diagnosed with non-surgically suitable PHNEC, confirmed through pathology. Following four cycles of standard first-line systemic chemotherapy, this intervention was prompted by imaging indicating suboptimal local lesion control, the patient underwent localized interventional and microwave ablation therapy. Subsequently, an evaluation based on mRECIST criteria revealed complete remission post-procedure. The disease sustained this remission status throughout the 14-month follow-up, with the administration of 14 cycles of immunocheckpoint inhibitor maintenance therapy, showing no signs of local recurrence or distant metastasis and devoid of any associated complications.Conclusion: This case introduces a novel therapeutic avenue for individuals who are ineligible for surgery and have not responded to systemic chemotherapy. The diagnosis and management of PHNEC are deliberated within the framework of this particular case.Keywords: primary hepatic neuroendocrine carcinoma, large cell, neuroendocrine carcinoma, interventional, liver

Hui Lian,1 Huacong Cai,2 Xiaoting Wang,3 Hongmin Zhang,3 Yuan Gao,4 Shuyang Zhang,5 Yan Zhang2 1Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Information Technology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of ChinaCorrespondence: Shuyang Zhang, Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email shuyangzhang103@163.com Yan Zhang, Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email zhangyan10659@pumch.cnBackground: Dysregulated host response is an important cause of critical illness. Coagulation reaction is the most primitive response and can be used to assess patient status. Coagulation reactions may be amplified in very old patients (VOPs). This study aimed to demonstrate coagulation reactions in critically ill VOPs by linking cytokines, coagulation, and fibrinolytic processes.Methods: We analyzed 33 critically ill VOPs admitted to our hospital, with an average age of 91.97. Laboratory test results were collected and double checked. In-hospital mortality, Intensive Care Unit (ICU) stay, and length of in-hospital stay (LOS)-associated variables were assessed using a generalized additive mix model. Smooth curves and interaction tests were used to quantify statistical interactions.Results: The in-hospital mortality rate was 45.5% in this study. The D-dimer level was correlated with ICU stay [risk ratio (RR), 1.39; 95% confidential interval (CI), 1.16– 1.67] and LOS (RR, 1.75; 95% CI, 1.19– 2.57). Other function or quantity indices, such as platelet (PLT), prothrombin time (PT), activated partial prothrombin time (APTT), and thrombomodulin (TM), were all correlated with clinical outcomes. After the link between coagulation reaction and the outcomes was constructed, it was revealed that, compared to lower level of IL-6, under high level of IL-6, elevated TM was likely to be associated with tissue plasminogen activator inhibitor complex (t-PAIC) elevation, which probably promoted the production of D-dimer (RR, 3.216; 95% CI, 1.840– 4.592).Conclusion: D-dimer levels are associated with outcomes in VOPs with critical illness. There is a certain link between inflammatory cytokines and the coagulation process. Under high IL-6 levels, the elevated TM may contribute to the increased t-PAIC, which contributes to the higher D-dimer level. Conversely, under low IL-6 levels, elevated TM levels are associated with reduced t-PAIC levels.Keywords: blood coagulation, very old patients, VOPs, critical illness, in-hospital mortality

Xiaolong Li,1 Xinyi Hou,2 Siqin Zhang,1 Jianming Xiong,1 Yuanyuan Li,2,3 Wenjun Miao1,4 1School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, People’s Republic of China; 2School of Pharmacy, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 3NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 4State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, People’s Republic of ChinaCorrespondence: Yuanyuan Li, School of Pharmacy, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China, Tel/Fax +86-0898-66968120, Email liyuanyuan@hainmc.edu.cn Wenjun Miao, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, People’s Republic of China, Tel/ Fax +86-25-58139942, Email miaowj@njtech.edu.cnPurpose: Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES).Methods: To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against Acinetobacter baumannii (A. baumannii) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo.Results: ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL− 1 of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating A. baumannii-induced acute peritonitis, accompanied by good biocompatibility in vivo.Conclusion: Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.Keywords: Gram-negative bacterial infection, multidrug-resistant, photodynamic therapy, oxygen affording, long circulation

Yidong Jin,1 Han Zhang,2 Min Zhou,1 Shaojun Zhang,1 Mi Guo1 1Emergency Department, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of China; 2Department of Neurosurgery, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mi Guo, Emergency Department, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of China, Email szguomi123@126.comBackground: Mixed lineage kinase domain-like protein (MLKL), which modulates necroptosis, has been implicated in pathophysiological processes following acute brain injury. Here, serum MLKL was quantified to determine its prognostic significance in severe traumatic brain injury (sTBI).Methods: This prospective cohort study enrolled 155 patients with sTBI and 155 healthy volunteers. The severity metrics included the Glasgow Coma Scale (GCS) score and Rotterdam computed tomography (CT) classification. The extended Glasgow outcome scale (GOSE) at posttraumatic 180 days was considered as a prognostic parameter, with a score of 1– 4 as indicating poor prognosis. Univariate and subsequent multivariate analyses were used for independent factorial investigation.Results: Compared to controls, patients displayed profoundly elevated serum MLKL levels. In the framework of restricted cubic spline analysis, serum MLKL levels were linearly correlated with the likelihood of mortality, overall survival, and poor prognosis. Serum MLKL levels were not only independently correlated with GCS, Rotterdam CT scores and GOSE scores, but were also independently predictive of death, overall survival, and poor prognosis. Subgroup analysis showed that serum MLKL levels exhibited negligible interactions with age, sex, hypertension, diabetes, smoking habits, and alcohol consumption to distinguish the possibility of death, overall survival, and poor prognosis. Within the context of receiver operating characteristic curve analysis, serum MLKL levels had strong discrimination effectiveness for death and poor prognosis and, in contrast to GCS and Rotterdam CT scores, were considered to have equivalent predictive ability.Conclusion: Extreme elevation of serum MLKL levels is intimately related to trauma severity, death, and neurological outcomes, suggesting that serum MLKL may act as a potential predictor for facilitating severity stratification and prognosis prediction of sTBI.Keywords: traumatic brain injury, mixed lineage kinase domain-like protein, severity, outcome, death, overall survival, biomarkers

Hui Lian,1,* Guangjian Wang,2,* Hongmin Zhang,2 Xiaoting Wang,2 Shuyang Zhang3 1Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoting Wang, Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email icuting@163.com Shuyang Zhang, Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email shuyangzhang103@163.comBackground: The host response plays a critical role in the progression of all critical illnesses, especially in the aging population. With aging becoming a global phenomenon, understanding changes in the host response among elderly patients can provide valuable insights for diagnosis and treatment in the ICU.Methods: This study included all patients aged 65 and older admitted to our geriatric intensive care unit (GICU). Demographic, clinical, and medication data were extracted from electronic medical records. The primary outcome was in-hospital mortality, while secondary outcomes included hospital length of stay (LOS) and ICU stay duration. We employed the generalized additive mixed model for analysis and utilized nomogram analysis to build a predictive mortality model.Results: A total of 1204 patients, with a median age of 75 years and a maximum age of 110 years, were admitted to the GICU. Host response biomarkers were notably lower in patients over 85 years. White blood cell (WBC) count, lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were positively associated with mortality, while a higher platelet-to-lymphocyte ratio (PLR) was inversely related to mortality. Lymphocyte count was identified as a significant risk factor for mortality (RR = 1.2181). Elevated host response biomarkers were inversely associated with both hospital and ICU LOS. The predictive model integrating these biomarkers exhibited strong predictive performance for mortality.Conclusion: Our findings underscore the significant impact of aging on host response in critically ill patients. Older patients, particularly those over 85, exhibited lower biomarker levels and higher mortality rates. The predictive model developed from inflammatory, immune, and coagulation markers demonstrated robust prognostic utility, aiding in the evaluation of critically ill elderly patients.Keywords: host response, critically ill, old patients, immune response, inflammatory response, procoagulant response

Yihui Yu,1 Wei Li,1,2 Qian Li,1,2 Wenyan Liu,1,2 Sanquan Zhang,1,2 Xibao Zhang,1,2 Jingyao Liang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of ChinaCorrespondence: Jingyao Liang; Xibao Zhang, Email ljy20221228@163.com; gzpfbfzs@163.comAbstract: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. The treatment of vitiligo remains challenging, partly owing to the lack of efficient drug delivery system. Microneedles (MNs), an ideal transdermal drug delivery system, have emerged as promising drug delivery platform for vitiligo. Recently, the emergence of novel MNs with increased biocompatibility, including hydrogel and hollow MNs, further enhance the translational value of MNs in the treatment of vitiligo. However, up-to-date review of these advancements remains lacking. This review aims to summarize the most recent studies of MN-based drug delivery systems for vitiligo, highlighting the translational potential of MNs as a therapeutic platform for the treatment of vitiligo in the near future. Keywords: vitiligo treatment, microneedle design, advanced applications

Shiyao Zhang,1 Xiuying Zhang,2 Chenghao Wei,1 Lai Zhang,1 Zhaoyang Li1 1Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 2The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xiuying Zhang, Email pcxtcm@163.comObjective: To investigate the causal relationship between 91 circulating inflammatory proteins and Various asthma phenotypes by means of Mendelian randomization.Methods: Genome-wide association Studies (GWAS) of 91 inflammatory proteins were pooled from the Olink Target platform with 14,824 participants. Various asthma phenotypes were derived from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the main method for MR Analysis, supplemented by Mr-Egger, Weighted median, Simple mode, and Weighted mode. The MR-Egger intercept term test and Cochran’s Q test were used to test the polymorphism and heterogeneity of IVs, and visual analysis was carried out to draw scatter plots, funnel plots, and leave-out-one plots. The FDR correction was performed due to the possibility of a type 1 error.Results: Genetically predicted IVW results revealed a total of 30 data sets suggesting a potential causal relationship between circulating inflammatory proteins and asthma phenotypes. Among them, 2 results were still strongly positive after FDR correction. The level of CST5 (OR=1.184; 95% CI: 1.075– 1.305; P=0.0001; P-FDR=0.028) is associated with an increased risk of non-allergic asthma. LIF-R (OR=0.723; 95% CI: 0.620– 0.842; P=0.000; P-FDR=0.003) is associated with a reduced risk of asthma in children. There was no pleiotropy or heterogeneity in the remaining 16 results that suggested a potential causal relationship.Conclusion: Increased CST5 levels are associated with an increased risk of non-allergic asthma. LIF-R is associated with a reduced risk of asthma in children.Keywords: mendelian randomization, inflammatory protein, asthma, childhood asthma, allergic asthma, non-allergic asthma, suggestive for eosinophilic asthma, obesity related asthma

Hongling Du,1– 3 Shunjie Zhang,1 Kezhu Yuan,4 Zhirui Yang,5 Mingquan Wu4 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pharmacy, Sichuan Public Health Clinical Center, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, Chengdu Second People’s Hospital, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Mingquan Wu, Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, People’s Republic of China, Email 18782976939@163.comBackground: Rehmanniae Radix (RR) has received attention for its antithrombotic effect. However, few studies have independently explored the bioactive components responsible for its antithrombotic bioactivity and the potential mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using metabolomics integrated with network pharmacology.Methods: A thrombosis model was established by intraperitoneal injection of type I carrageenan in rats, and antithrombotic function was evaluated at different doses of RR. Metabolomics was used to identify the differential metabolites in the serum. Network pharmacology was then applied to identify the potential targets for the antithrombotic activity of the RR. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape. Finally, key targets were verified using molecular docking.Results: RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen potentially significant metabolites were involved in the therapeutic effects of RR against thrombosis, most of which were regulated for recovery after RR treatment. An integrated analysis of metabolomics and network pharmacology showed that the antithrombosis effect of RR was closely associated with the regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high affinity between the key targets and components of RR. We speculated that the components of RR, such as catalpol, ferulic acid methyl ester, and methyl 4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and ALOX5, to exert antithrombosis effects.Conclusion: This study confirmed the antithrombotic effect of high-dose RR, revealed the antithrombotic mechanism and potential material basis, and laid the foundation for the antithrombotic clinical application of RR. Furthermore, it provides a successful case reference for screening natural herbal components and exploring their potential pharmacological mechanisms.Keywords: Rehmanniae radix, antithrombotic effects, metabolomics, network pharmacology

Dandan Wang,1– 3,* Jingguo Wang,3,* Zequn Yin,4 Ke Gong,3 Shuang Zhang,3 Zhengbao Zha,3 Yajun Duan4 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230011, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 3School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230601, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengbao Zha, School of Food and Biological Engineering, Hefei University of Technology, No. 420 Feicui Road, Hefei, Anhui, 230601, People’s Republic of China, Email zbzha@hfut.edu.cn Yajun Duan, Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui, 230031, People’s Republic of China, Email yajunduan@ustc.edu.cnIntroduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD. In this study, we synthesized polyoxometalates (POM) for potential treatment of MASLD.Methods: We induced liver disease in mice using two approaches: feeding a high-fat diet (HFD) to establish MASLD or feeding a methionine–choline deficient (MCD) diet to induce hepatic lipotoxicity and MASH. Various metabolic parameters were detected, and biochemical and histological evaluations were conducted on MASLD. Western blotting, qRT-PCR and immunofluorescence assays were used to elucidate the molecular mechanism of POM in the treatment of MASLD.Results: POM therapy resulted in significant improvements in weight gain, dyslipidemia, liver injury, and hepatic steatosis in mice fed a HFD. Notably, in a more severe dietary-induced MASH model with MCD diet, POM significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis. POM treatment effectively attenuated palmitic acid and oleic acid-induced lipid accumulation in HepG2 and Huh7 cells by targeting the AMPK pathway to regulate lipid metabolism, which was confirmed by AMPK inhibitor. Additionally, the activation of AMPK signaling by POM suppressed the expression of lipid synthesis genes, including sterol regulatory element-binding protein 1c (SREBP1c) and SREBP2, while concurrently upregulating the expression of sirtuin 1 (SIRT1) to promote fatty acid oxidation.Conclusion: These findings suggest that POM is a promising therapeutic strategy with high efficacy in multiple MASLD models. Keywords: polyoxometalates, MASLD, MASH, AMPK, lipotoxicity

Shenghao Zhang,1,* Jiahui Ma,1,* Yilei Ma,1,* Jia Yi,1 Beier Wang,2 Hanbing Wang,3 Qinsi Yang,4 Kun Zhang,5 Xiaoqing Yan,6 Da Sun,1,7 Jinfeng You8 1Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, People’s Republic of China; 2Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Biotechnology, The University of Hong Kong, Hong Kong SAR, 999077, People’s Republic of China; 4Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, People’s Republic of China; 5Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 6The Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Department of Endocrinology, Yiwu Central Hospital, The Affiliated Yiwu hospital of Wenzhou Medical University, Yiwu, 322000, People’s Republic of China; 8Department of Obstetrics, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinfeng You; Da Sun, Email Jincancanyjf@163.com; sunday@wzu.edu.cnBackground: Diabetes Mellitus (DM) is a substantial health concern worldwide, and its incidence is progressively escalating. Conventional pharmacological interventions frequently entail undesirable side effects, and while probiotics offer benefits, they are hindered by constraints such as diminished stability and effectiveness within the gastrointestinal milieu. Given these complications, the advent of bioengineered probiotics is a promising alternative for DM management.Aim of Review: The objective of this review is to provide an exhaustive synthesis of the most recent studies on the use of engineered probiotics in the management of DM. This study aimed to clarify the mechanisms through which these probiotics function, evaluate their clinical effectiveness, and enhance public awareness of their prospective advantages in the treatment of DM.Key Scientific Concepts of Review: Scholarly critiques have explored diverse methodologies of probiotic engineering, including physical alteration, bioenrichment, and genetic manipulation. These techniques augment the therapeutic potency of probiotics by ameliorating gut microbiota, fortifying the intestinal barrier, modulating metabolic pathways, and regulating immune responses. Such advancements have established engineered probiotics as a credible therapeutic strategy for DM, potentially providing enhanced results compared to conventional treatments. Keywords: engineered probiotics, diabetes mellitus, gut microbiota, genetic engineering, therapeutic efficacy

Xiao-Yang Xu,&ast; Ze Wang,&ast; Chen-You Liu,&ast; Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Street, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comObjective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5– 32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3−CD19+ (p=0.004), CFB (p=0.027), NLR (p< 0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.Keywords: immune indicator, TACE, immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor microenvironment

Chunlei Tan,1 Jinling Xu,2 Shiyuan Zhang,1 Shuqiang Liu,1 Xiaotian Yang,1 Danping Wu,1 Boqian Yu,1 Yuanxi Huang1 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Endoscope Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of ChinaCorrespondence: Yuanxi Huang, Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China, Tel/Fax +86-0451-86298053, Email rxwk@163.comPurpose: The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.Patients and Methods: A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher’s exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan–Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.Results: Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P< 0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P< 0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595– 4.992, P< 0.0001; OS: HR: 3.232, 95% CI: 1.812– 5.763, P< 0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.Conclusion: FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.Keywords: breast cancer, FOXP3, chemotherapy, radiotherapy, survival

Zixuan Zhang,1 Jing Bai,1 Siqi Zhang,1 Renzhen Wang,1 Shaobing Zhu,1 Tianyue Li,1 Miao Zhang2 1Graduate Schools, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Miao Zhang, Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13845088833, Fax +86-13114600132, Email hljzmzjzy@163.comAbstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease caused by multiple causes. The main pathological features of AD are β-amyloid (Aβ) deposition, hyperphosphorylation of Tau protein, and progressive neuronal loss. Pyroptosis is one of the main forms of neuronal death, which is mainly caused by the activation of Gasdermin protein by upstream signals and the release of its N-terminal domain on the cell membrane. Studies have shown that there is a close relationship between Alzheimer’s disease (AD) and pyroptosis. Therefore, this paper summarizes the relationship between pyroptosis and its molecular mechanism and AD, as well as the related research of traditional Chinese medicine in the treatment of AD by regulating pyroptosis, in order to provide a new direction for the study of AD pathogenesis based on pyroptosis pathway.Keywords: Alzheimer’s disease, cell pyroptosis, inflammasome, traditional Chinese medicine

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

Huaqiong Wu,1,&ast; Guifen Yang,2,&ast; Shaohua Zhang,2 Jinxiang Luo,1 Pei Zhou,1 Yuhua Chen1 1Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Zhang, Department of Internal Medicine-Cardiovascular, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8618062579072, Email zhangshaohua1258@163.com Jinxiang Luo, Department of Radiodiagnosis, Central War Zone General Hospital of Wuhan, No. 627, Wuluo Road, Wuchang District, Wuhan, Hubei, 430070, People’s Republic of China, Tel +8602750773333, Email luojinxiang2020@21cn.comObjective: To investigate the correlation between risk factors for coronary stenosis and the degree of coronary artery stenosis based on coronary computed tomography angiography (CCTA).Methods: Two hundred seventy-eight patients with coronary artery disease who received treatment in our hospital between January 2020 and January 2021 were selected as the experimental group, and 100 healthy people who received physical examination in our hospital during the same period were selected as the control group (age and gender matched with the study group). The clinical data and CCTA data of the two groups of patients were collected and compared. Computed tomography fractional flow reserve (FFRCT) values were calculated based on the CCTA data of the patients in the study group, risk factors for coronary artery stenosis were analysed and the correlation between the risk factors and CT flow reserve fraction was explored.Results: The serum total bilirubin (BIL), apolipoprotein A (apoA), low-density lipoprotein cholesterol (LDL-C), uric acid, total cholesterol (TC) and mean platelet volume levels were higher in the experimental group than in the control group (P < 0.05). Unconditional logistic regression analysis showed that LDL-C, uric acid, TC, triglyceride, serum total BIL and apoA were independent risk factors for coronary heart disease (P < 0.05). Serum total BIL (r = 0.27), apoA (r = − 0.30), uric acid (r = − 0.48), TC (r = − 0.35), triglyceride (r = − 0.73) and LDL-C (r = − 0.65) showed a negative correlation with FFRCT values (P < 0.05). A positive correlation was detected between high-density lipoprotein cholesterol and FFRCT values (r = 0.37, P < 0.05).Conclusion: Triglycerides, LDL-C, uric acid, TC, serum total BIL and apoA are risk factors for coronary artery stenosis that should be closely monitored and receive active intervention in clinical practice.Keywords: coronary heart disease, coronary artery stenosis, computed tomography angiography, risk factors, computed tomography fractional flow reserve

Dengliang Ji,1 Jiulong Li,2 Andong Liu,3 Ruiping Ye,4 Shengrui Zhang,5 Lin Gao,5 Zhenfei Huang5 1Department of Intensive Care Unit, Ganzhou Fifth People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Intensive Care Unit, Ningdu County Chinese Medicine Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 3Department of Intensive Care Unit, Suichuan County Chinese Medicine Hospital, Jian, Jiangxi, 343000, People’s Republic of China; 4Department of Intensive Care Unit, Dingnan County First People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 5Department of Intensive Care Unit, GanZhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaCorrespondence: Zhenfei Huang, Department of Intensive Care Unit, GanZhou People’s Hospital, No. 16 Meiguan Avenue, Zhanggong District, Ganzhou, Jiangxi, 341000, People’s Republic of China, Email fishyugz129@sina.comObjective: This study aims to investigate the effectiveness of combining serum lectin galactoside-binding soluble 3 binding protein (LGALS3BP) with growth differentiation factor 15 (GDF-15) for predicting outcomes in sepsis patients in an intensive care unit (ICU) setting.Methods: The study involved 208 sepsis patients from the ICU of our hospital. These patients were categorized based on their 28-day survival outcomes into two groups: 166 in the survival group and 42 in the mortality group. The serum levels of LGALS3BP and GDF-15 were measured using the ELISA technique. Pearson and Spearman methods were utilized for correlation analysis. Factors affecting mortality in ICU sepsis patients were evaluated through multivariate logistic regression analysis. The efficacy of these biomarkers in prognosis prediction was assessed using receiver operating characteristic (ROC) curve analysis.Results: The proportion of septic shock, APACHE II score, SOFA score, and serum LGALS3BP and GDF-15 levels in ICU sepsis patients in the death group were obviously higher than those in the survival group (P< 0.05). The severity of ICU sepsis patients, APACHE II score, and SOFA score were obviously positively correlated with serum LGALS3BP and GDF-15 levels (P< 0.05). LGALS3BP (OR: 95% CI=2.745:1.583~4.761) and GDF-15 (OR: 95% CI=2.639:1.423~4.893) were independent risk factors for death in ICU sepsis patients (P< 0.05). The AUC of serum LGALS3BP and GDF-15 levels alone in predicting death in ICU sepsis patients was 0.859 and 0.854, obviously lower than the AUC of the combination, 0.943 (Z=2.704, 2.287, P< 0.05). The AUC for predicting mortality in ICU sepsis patients using the APACHE II and SOFA scores were 0.832 and 0.842, respectively. The differences in comparison to the AUCs of LGALS3BP and GDF-15 were not statistically significant (P > 0.05).Conclusion: Serum levels of LGALS3BP and GDF-15 can both be used as predictive indicators for death in ICU sepsis patients, and their combined predictive efficacy is better.Keywords: sepsis, intensive care unit, lectin galactoside-binding soluble 3 binding protein, growth differentiation factor 15, prognosis

Shenghao Zhang,1,&ast; Zhejianyi Gao,2,&ast; Lina Feng,1,3 Mingquan Li1 1Department of Neurology, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, 130021, People’s Republic of China; 2Department of Orthopaedics, Fushun Hospital of Chinese Medicine, Fushun, Liaoning Province, 113008, People’s Republic of China; 3Shandong Key Laboratory of TCM Multi-Targets Intervention and Disease Control, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Feng; Mingquan Li, Department of Neurology, the Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-15543120222 ; +86-15948000577, Email Fenglina0001@163.com; Limingquan0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease characterized by its insidious onset and progressive development, making it the most common form of dementia. Despite its prevalence, the exact causes and mechanisms responsible for AD remain unclear. Recent studies have highlighted that inflammation in the central nervous system (CNS) plays a crucial role in both the initiation and progression of AD. Neuroinflammation, an immune response within the CNS triggered by glial cells in response to various stimuli, such as nerve injury, infection, toxins, or autoimmune reactions, has emerged as a significant factor alongside amyloid deposition and neurofibrillary tangles (NFTs) commonly associated with AD. This article aims to provide an overview of the most recent research regarding the involvement of neuroinflammation in AD, with a particular focus on elucidating the specific mechanisms involving microglia and astrocytes. By exploring these intricate processes, a new theoretical framework can be established to further probe the impact of neuroinflammation on the development and progression of AD. Through a deeper understanding of these underlying mechanisms, potential targets for therapeutic interventions and novel treatment strategies can be identified in the ongoing battle against AD.Keywords: alzheimer’s disease, neuroinflammation, microglia, astrocyte, review

Yaxin Wang,1 Ziyang Wang,2 Yin Sun,1 Lin Yang,2 Liangkun Ma,1 Jiao Li,2 Suhan Zhang,1 Xuanjin Yang1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, PUMC Hospital, CAMS and PUMC, Beijing, People’s Republic of China; 2Institute of Medical Information/Medical Library, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100020, People’s Republic of ChinaCorrespondence: Yin Sun, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Email sunyin@pumch.cnObjective: The study aimed to obtain more evidence on the association of gestational weight gain and pre-pregnancy body mass index (BMI) with macrosomia.Methods: The data on 5409 live births delivered at Peking Union Medical College Hospital from July 2020 to June 2022 were collected. Group analyses were performed according to the presence or absence of macrosomia. Multivariable binary logistic regression and incidence heatmaps was used to analyze the related factors of macrosomia.Results: The following variables were significantly associated with macrosomia: overweight (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.62– 3.10), obesity (OR: 4.56, 95% CI: 2.93– 6.98), excessive gestational weight gain (OR: 2.39, 95% CI: 1.67– 3.43), gestational age at delivery at 39– 41 weeks (OR: 3.83, 95% CI: 2.56– 5.95), gestational age at delivery over 41 weeks (OR: 7.88, 95% CI: 4.37– 14.19), education level of junior college or below (OR: 1.95, 95% CI: 1.19– 3.09), and multipara (OR: 1.62, 95% CI: 1.09– 2.42). “v” represents the mean weekly weight gain during the second and third trimesters. A higher v value increased the risk of macrosomia by 2.6-fold (95% CI: 1.37– 4.89, P = 0.003). Compared to normal weight women, after adjustment for different pre-pregnancy BMI subgroups, overweight pregnant women had higher weekly weight gain in the second and third trimesters (OR: 4.57, 95% CI: 2.27– 9.10, P < 0.001). Obese pregnant women had higher average weekly weight gain during the second and third trimesters, and the OR value for macrosomia was 11.33 (95% CI: 4.95– 25.18, P < 0.001). To reduce the incidence of macrosomia in overweight pregnant women, v = 0.32 could be considered the critical threshold of average weekly weight gain in these women in the second and third trimesters of pregnancy.Conclusion: Pre-pregnancy BMI and weight gain during pregnancy are closely related to macrosomia. The introduction of average weekly weight gain values in the second and third trimesters of pregnancy probably help pregnant women minimizing adverse pregnancy-related outcomes.Plain Language Summary: What is already known about this topic?Pre-pregnancy BMI and GWG are both risk factors for macrosomia. It is very important to develop effective interventions based on pathogenic factors to promote the health of mothers and children. However, the threshold for maternal weight control in the second and third trimesters of pregnancy is unclear.What is added by this report?Our data suggest that the critical threshold of average weekly weight gain in overweight pregnant women during the second and third trimesters 0.32kg per week is beneficial to reduce the incidence of macrosomia.What are the implications for public health practice?The results of this study highlight the importance of weight management in women in the second and third trimesters, especially those who are overweight, and reasonable control of weight gain will contribute to maternal and fetal health.Keywords: pregnancy, pre-pregnancy BMI, gestational weight gain, macrosomia, critical threshold of weight gain

Qiang Guo,1,&ast; Yang Xiao,2,&ast; Jing Chu,3 Yu Sun,2 Shaomei Li,3 Shihai Zhang1 1Department of Clinical Laboratory, Anhui Children’s Hospital, Hefei, People’s Republic of China; 2Xuhzou Medical University, Jiangsu, People’s Republic of China; 3Department of Pathology, Anhui Children’s Hospital, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihai Zhang, Department of Clinical Laboratory, Anhui Children’s Hospital, Wangjiang Road 39, Hefei, People’s Republic of China, Tel +86– 13856048692, Email zhangshihai888@126.comObjective: This study aims to identify differentially expressed genes (DEGs) in neuroblastoma (NB) through comprehensive bioinformatics analysis and machine learning techniques. We seek to elucidate these DEGs’ biological functions and associated signaling pathways. Furthermore, our objective extends to predicting upstream microRNAs (miRNAs) and relevant transcription factors of pivotal genes, with the ultimate goal of guiding clinical diagnostics and informing future treatment strategies for Neuroblastoma.Methods: In this study, we sourced datasets GSE49710 and TARGET from the GEO and UCSC-XENA databases, respectively. Differentially expressed genes (DEGs) were identified using the R language “limma” package. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs were conducted using the “clusterProfiler” package. We employed Weighted Gene Co-expression Network Analysis (WGCNA) to isolate the most significant modules associated with death and MYCN amplification, specifically MEpink and MEbrown modules. These modules were then cross-referenced with the DEGs for further GO and KEGG pathway analyses. LASSO regression analysis, facilitated by the “glmnet” package, was utilized to pinpoint three hub genes. We performed differential analysis on these genes and constructed Receiver Operating Characteristic (ROC) curves for disease diagnosis purposes. Immune infiltration analysis was conducted using the “GSVA” package’s ssGSEA function. Additionally, single-gene Gene Set Enrichment Analysis (GSEA) on the hub gene was carried out based on Reactome and KEGG databases. Upstream miRNA and transcription factors associated with the hub gene were predicted using RegNetwork, with visual representations created in Cytoscape. Furthermore, to validate the three identified markers in neuroblastoma tissues, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis was conducted.Results: We identified 483 differentially expressed genes (DEGs) in neuroblastoma. These genes predominantly function in protein translation, membrane composition, and RNA transcription regulation, and are implicated in multiple signaling pathways relevant to neurodegenerative diseases. Utilizing LASSO regression analysis, we pinpointed three hub genes: VGF, DGKD, and C19orf52. The Receiver Operating Characteristic (ROC) curve analysis yielded Area Under Curve (AUC) values of 0.751 and 0.722 for VGF, 0.79 and 0.656 for DGKD, and 0.8 and 0.753 for C19orf52, respectively. Our immune infiltration analysis revealed significant correlations among monocytes, follicular helper T cells, and CD4+ T cells. Notably, in the death group, we observed heightened infiltration levels of activated CD4+ T cells, macrophages, and Th2 cells. C19orf52 exhibited a close association with the infiltration of monocytes, CD4+ T cells, and Th2 cells, with P-values less than 0.05. Furthermore, qRT-PCR analysis corroborated the upregulation of VGF in neuroblastoma tissues, further validating our findings.Conclusion: The hub genes (VGF, DGKD, and C19orf52) of neuroblastoma are screened. VGF, one of the hub genes, may have a high diagnostic value and is involved in the immune cell infiltration in neuroblastoma tissue, which may be used as a biomarker for the diagnosis of neuroblastoma and provides a new direction for clinical prognosis prediction and management improvement. Keywords: neuroblastoma, WGCNA, LASSO regression, bioinformatics analysis

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

Siqin Zhang,1,&ast; Songsong Tan,1,&ast; Bin Yang,2 Yaoyao Wu,3 Guohang Yuan,3 Fengjiao Chen,4 Lin Liu3,5 1Department of Endocrinology and Metabolism, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 2Department of Central Laboratory, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 3Department of Respiratory and Critical Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 4Research Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 5NHC Key Laboratory of Pulmonary Immunological Diseases (Guizhou Provincial People’s Hospital), Guiyang, Guizhou, 550002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Liu, Department of Respiratory and Critical Medicine, Guizhou Provincial People’s Hospital, NHC Key Laboratory of Pulmonary Immunological Diseases (Guizhou Provincial People’s Hospital), No. 83, Zhongshan East Road, Guiyang, 550002, Guizhou, People’s Republic of China, Tel +86 28 18685109665, Fax +86 28 85423459, Email liulin0956@163.comObjective: Azvudine is used to treat patients with the coronavirus disease 2019 (COVID-19). This study evaluated the clinical efficacy of azvudine in hospitalized patients with different severities of COVID-19 because few studies have described this in patients with severe and non-severe COVID-19.Methods: This retrospective study included hospitalized patients with COVID-19 in Guizhou Provincial People’s Hospital between December 2022 and January 2023. Azvudine-treated patients and controls were matched for sex, age, and disease severity at admission. Laboratory results and outcomes, including all-cause mortality, invasive mechanical ventilation, intensive care unit admission, and hospital stay length, were evaluated. Stratified analysis was used to explore the difference in the efficacy of azvudine in severe and non-severe COVID-19 patients.Results: No significant differences in all-cause mortality were observed between the 303 azvudine recipients and 303 matched controls. However, azvudine-treated patients had shorter hospital stays (8.34± 4.79 vs 9.17± 6.25 days, P=0.046) and higher lymphocyte improvement rates (21.5% vs 13.9%, P=0.019), with a more pronounced effect in patients with non-severe COVID-19 (length of hospital stay, 8.07± 4.35 vs 10.00± 6.29 days, P=0.001; lymphocyte improvement rate, 23.8% vs 12.8%, P=0.015).Conclusion: Azvudine treatment shortens hospital stay length and increases the rate of lymphocyte count improvement in patients with non-severe COVID-19, suggesting that azvudine may be a treatment option for these patients.Keywords: azvudine, COVID-19, severity, effectiveness, clinical outcome, hospital stay length

Shangtao Wang,1 Chenghao Zhu,1 Shurui Zhang,1 Siyu Ma,1 Baoshan Li,1 Shengbo Zhao,2 Wei Zhang,3 Zhirong Sun1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Ningqiang Tianma Research Institution Limited Liability Company, Hanzhong, Shaanxi, People’s Republic of China; 3Ningqiang County Traditional Chinese Medicinal Industry Development Center, Hanzhong, Shaanxi, People’s Republic of ChinaCorrespondence: Zhirong Sun, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Yangguang South Street and Baiyang East Road, Fangshan District, Beijing, 102401, People’s Republic of China, Email szrbucm67@163.comBackground: Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear.Objective: This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms.Methods: The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting.Results: In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways.Conclusion: Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN. Keywords: gastrodin, gallic acid, synergistic effects, inflammation, apoptosis, sphingolipid pathways

Xiaoyan Hong,1 Yangrong Huang,1 Wei Lin,1 Yi Zhang,1 Jianyun Lin,1 Shengguo Zhang,2 Fengquan Cai,1 Jie Chen1 1Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of China; 2Department of Infection, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Fengquan Cai; Jie Chen, Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), 108 Wansong Road, Wenzhou, 325200, Zhejiang, People’s Republic of China, Tel +86-13967723666 ; +86-13587409966, Email cfqruiyi@163.com; woshichenjie@wmu.edu.cnAbstract: Staphylococcus aureus (S. aureus) infection is readily disseminated, yet the multiple septic arthritis and extensive migratory skin and soft tissue infections it causes are uncommon and challenging to treat. The infection can be life-threatening, with a mortality rate of 15– 31%. Early, targeted antibiotic therapy is critical to improve prognosis. However, routine cultures are time-consuming and have low positivity rates, which may lead to errors in antibiotic regimen selection, depriving patients of optimal treatment. Genetic testing technologies, such as macrogenomic next-generation sequencing (mNGS) and digital polymerase chain reaction (dPCR), are now emerging as powerful tools for early pathogen diagnosis as well as pathogen diagnosis of target detectors with low microbial loads. In this study, we report a 53-year-old man who was admitted to the ICU for treatment of septic shock. The causative agent was targeted earlier as S. aureus by mNGS, and the shock was corrected more quickly with targeted antibiotic medication. However, he later developed multiple septic arthritis and an extensive migratory skin soft tissue infection with persistent fever, and at one point a gram-negative bacterial infection was suspected, and the antibiotic regimen was incorrectly changed. Blood dPCR suggested that the causative organism was still methicillin-sensitive S. aureus (MSSA), with no drug resistance gene detected, and the anti-infective regimen was readjusted, and the patient eventually recovered and was discharged from the hospital. We present this rare case and review related studies to validate the superiority of genetic testing technology in pathogen diagnosis, which deserves further application.Keywords: disseminated Staphylococcus aureus disease, multiple suppurative arthritis, extensive migratory skin and soft tissue infections, digital polymerase chain reaction, next-generation sequencing

Shiyu Zhang, Fanting Kong, Lei Zheng, Xiaowei Li, Lining Jia, Lixian Yang Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixian Yang, Department of Breast Surgery, Xingtai People’s Hospital, No. 818 Xiangdu District, Xingtai, Hebei, 054000, People’s Republic of China, Email yanglixian@hebmu.edu.cnBackground: The role of Semaphorin 7a (SEMA7A) in the initiation and progression of different types of cancerous lesions has been extensively studied. However, the prognostic significance of SEMA7A, specifically in breast cancer (BC), lacks clarity.Methods: We conducted an evaluation on the relationship between SEMA7A and the prognosis, immune invasion and tumor mutation burden in different types of cancer by analyzing data from The Cancer Genome Atlas database. The present study focused on investigating the expression level, mutation, immune correlation and coexpression of SEMA7A in BC, utilizing various databases such as the University of Alabama at Birmingham Cancer data analysis portal, cBioPortal and tumor immune estimation resource. Survival analysis was carried out using the Kaplan-Meier Plotter. Furthermore, we employed the R software package to generate receiver operating characteristic (ROC) curves and nomograms. Notably, P< 0.05 was considered to indicate statistical significance.Results: Using pancancer analysis, it has been observed that the expression of SEMA7A is elevated in various types of cancer and is strongly correlated with the prognosis of different cancer types. SEMA7A also exhibits a significant association with the tumor mutation burden of diverse types of cancer. Moreover, SEMA7A displays a notable increase in BC cases, and was indicated to have a substantial association with the abundance of immune infiltration. In-depth survival analysis demonstrated that elevated levels of SEMA7A expression are notably linked to shorter overall survival and distant metastasis-free survival among patients with BC. The efficiency of SEMA7A as a reliable prognostic biomarker for BC has been substantiated by the validation of ROC curves and nomograms.Conclusion: SEMA7A has the potential to function as a prognostic indicator for BC, and its correlation with immune infiltration in BC is significant.Keywords: SEMA7A, breast cancer, biomarker, prognosis, methylation, immune infiltration, nomogram, bioinformatics

Yuhang Tian,1 Xiang He,1 Yanchi Yuan,1 Shijie Zhang,2 Chunyue Wang,1 Jialin Dong,1 Zhao Liu,1 Hui Jing1 1Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of ChinaCorrespondence: Hui Jing, Department of Ultrasound, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, People’s Republic of China, Email jinghuihrb@163.comBackground: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities.Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37.Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability.Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.Keywords: mild photothermal therapy, gene therapy, ferroptosis, synergistic therapy, multimodal imaging

Xue Yang,1,&ast; Man Wu,2,&ast; Tangzhiming Li,3,&ast; Jie Yu,4 Tian Fu,5 Guoping Li,6 Huanwen Xiong,7 Gang Liao,8 Sensen Zhang,9 Shaofeng Li,10 Zhonghua Zeng,11 Chun Chen,12 Benhui Liang,13,14 Zhiguo Zhou,15 Ming Lu16 1Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen People’s Hospital (The Second Clinical Medical College, The First Affiliated Hospital, Southern University of Science and Technology, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Jining No 1. People’s Hospital, Jining, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongde Hospital of Zhejiang Hangzhou, Zhejiang, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, People’s Republic of China; 9Department of Respiratory Medicine, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Fuzhou, Jiangxi, People’s Republic of China; 12Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 13Department of Cardiology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 14Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 15Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China; 16Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiguo Zhou, Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China, Email zhouzhiguo1217@163.com Ming Lu, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email 602032934@qq.comIntroduction: C. psittaci pneumonia has atypical clinical manifestations and is often ignored by clinicians. This study analyzed the clinical characteristics, explored the risk factors for composite outcome and established a prediction model for early prediction of composite outcome among C. psittaci pneumonia patients.Methods: A multicenter, retrospective, observational cohort study was conducted in ten Chinese tertiary hospitals. Patients diagnosed with C. psittaci pneumonia were included, and their clinical data were collected and analyzed. The composite outcome of C. psittaci pneumonia included death during hospitalization, ICU admission, and mechanical ventilation. Univariate and multivariable logistic regression analyses were conducted to determine the significant variables. A ten-fold cross-validation was performed to internally validate the model. The model performance was evaluated using various methods, including receiver operating characteristics (ROC), C-index, sensitivity, specificity, positive/negative predictive value (PPV/NPV), decision curve analysis (DCA), and clinical impact curve analysis (CICA).Results: In total, 83 patients comprised training cohorts and 36 patients comprised validation cohorts. CURB-65 was used to establish predictive Model 1. Multivariate logistic regression analysis identified three independent prognostic factors, including serum albumin, CURB-65, and white blood cells. These factors were employed to construct model 2. Model 2 had acceptable discrimination (AUC of 0.898 and 0.825 for the training and validation sets, respectively) and robust internal validity. The specificity, sensitivity, NPV, and PPV for predicting composite outcome in the nomogram model were 91.7%, 84.5%, 50.0%, and 98.4% in the training sets, and 100.0%, 64.7%, 14.2%, and 100.0% in the validation sets. DCA and CICA showed that the nomogram model was clinically practical.Conclusion: This study constructs a refined nomogram model for predicting the composite outcome in C. psittaci pneumonia patients. This nomogram model enables early and accurate C. psittaci pneumonia patients’ evaluation, which may improve clinical outcomes.Keywords: Chlamydia psittaci pneumonia, nomogram, prediction model, composite outcome

Hui Tang,1 Xiurong Xing,1 Yingna Han,1 Daiquan Gao,2 Piu Chan,3 Shengfang Zhang,4 Huixin Xue4 1Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurobiology, Xuanwu Hospital of China Capital Medical University, Beijing, People’s Republic of China; 4School of Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hui Tang, Department of Emergency Internal Medicine, Xuanwu Hospital of China Capital Medical University, No. 45 of Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-1083198280, Email tanghui_202186@21cn.comObjective: To investigate the clinical characteristics, risk factors and outcomes of brain-heart syndrome (BHS) in patients with acute cerebrovascular diseases (ACVDs).Methods: A retrospective analysis was conducted of 100 patients who were admitted to our hospital with ACVDs between January 2023 and December 2023. The demographic, clinical, laboratory and imaging data of the patients were collected, and the presence and severity of BHS were evaluated. The neurological and cardiac outcomes of the patients at discharge and at 12-month follow-up were also assessed.Results: Out of the 100 patients, 38% had BHS, classified as mild (18%), moderate (12%) and severe (8%). The most prevalent ACVDs were cerebral infarction (58%), cerebral haemorrhage (32%) and subarachnoid haemorrhage (10%). Cardiac complications included arrhythmia (26%), myocardial ischaemia (18%) and heart failure (10%). Patients with BHS had higher results for blood pressure, heart rate, white blood cell count, C-reactive protein, IL-6, D-dimer and troponin, more severe neurological deficits, higher mortality and poorer functional outcomes. Multivariable analysis identified age, hypertension, diabetes, coronary artery disease, prior cardiovascular events, cerebral haemorrhage, brainstem infarction and hypothalamic or insular lesions as independent risk factors for BHS.Conclusion: Brain-heart syndrome is a frequent, severe complication in patients with ACVD, linked with multiple risk factors and poor prognosis. Prompt diagnosis and treatment are crucial for improving patient outcomes.Keywords: brain-heart syndrome, acute cerebrovascular diseases, cerebral infarction, cerebral haemorrhage

Huanhuan Wang,1,&ast; Dan Xiao,2,&ast; Hua Zhou,3,&ast; Shu Chen,4 Guangjun Xiao,4 Juan Hu,4 Hui Quan,2 Miao Luo,5 Shaocheng Zhang2,6 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, the Second Affiliated Hospital of Chengdu Medical College (Nuclear Industry 416 Hospital), Chengdu, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Laboratory Medicine, Suining Central Hospital, Suining, Sichuan, People’s Republic of China; 5Department of Laboratory Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 6School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaocheng Zhang; Miao Luo, Email 102024001@cmc.edu.cn; 536513878@qq.comPurpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance.Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median.Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers.Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.Keywords: Chinese visceral adiposity index, immune function, chronic inflammation, SARS-CoV-2 vaccine, neutralizing antibody

Yong Liu,1 Hui Liu,2 Queqiao Bian,1 Shuhuan Zhang,1 Yanmin Guan3 1Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 3Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yong Liu, Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, No. 83, Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Email liuyongtj@163.comBackground: Herpes zoster (HZ) and postherpetic neuralgia (PHN) significantly affect patients’ quality of life (QoL). Cultural differences may lead to different patient-reported outcomes across countries. The current study aims to evaluate the detrimental impact of HZ and PHN on QoL in China.Methods: This prospective study was conducted from January 2020 to April 2023. We used the Zoster Brief Pain Inventory (ZBPI) and 5-level EuroQol-5 Dimension (EQ-5D-5L) questionnaire to assess the QoL of HZ and PHN patients. Patients were required to complete the questionnaires at 15, 30, 60, and 90 days after the onset of the HZ rash. Additional questionnaires were administered at 120, 150, and 180 days for those who developed PHN within three months of the rash’s onset.Results: A cohort of 633 patients with a median age of 63 years were included in the study. The mean delay from the appearance of the initial HZ rash to the first medical consultation was 5.1 ± 2.8 days. Approximately 30% of the HZ patients (189/633) went on to develop PHN. For patients with HZ who did not progress to PHN, the ZBPI worst pain score and impaired QoL had nearly resolved by day 90 post-rash onset. Conversely, there was no significant improvement in the ZBPI worst pain score and QoL for those with PHN, even by day 180 post-rash onset.Conclusion: Both HZ and PHN significantly impaired patients’ QoL. However, the impairment caused by PHN was more severe in both intensity and duration.Keywords: herpes zoster, pain, post-herpetic neuralgia, quality of life

Jiayun Jiang,1 Hui Zhang,1 Jiejuan Lai,1 Shiyu Zhang,1 Yanjiao Ou,1 Yu Fu,2,&ast; Leida Zhang1,&ast; 1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leida Zhang, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email 2518569931@qq.com Yu Fu, Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Email fuyu2020@swu.edu.cnPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P< 0.001; Median PFS: 13.0 months vs 2.7 months, P< 0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P< 0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P< 0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number > 3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, lenvatinib, tislelizumab, immunotherapy

Heidi Chwan Ko,1,&ast; RJ Seager,2,&ast; Sarabjot Pabla,2 Maria-Fernanda Senosain,2 Erik Van Roey,2 Shuang Gao,2 Kyle C Strickland,1,3 Rebecca Ann Previs,1,4 Michelle F Green,1 Maureen Cooper,1 Mary K Nesline,1 Stephanie B Hastings,1 Kobina Agyaful Amoah,1 Shengle Zhang,2 Jeffrey M Conroy,2 Taylor J Jensen,1 Marcia Eisenberg,5 Brian Caveney,5 Eric A Severson,1 Shakti Ramkissoon,1,6 Shipra Gandhi7 1Labcorp Oncology, Durham, NC, USA; 2Labcorp Oncology, Buffalo, NY, USA; 3Department of Pathology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 4Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA; 5Labcorp, Burlington, NC, USA; 6Department of Pathology, Wake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA; 7Department of Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA&ast;These authors contributed equally to this workCorrespondence: Heidi Chwan Ko, Email Heidi.ko@labcorp.comBackground: The understanding of molecular characteristics of HER2-low breast cancer is evolving since the establishment of trastuzumab deruxtecan. Here, we explore the differences in expression patterns of immune-related genes in the tumor immune microenvironment (TME) and survival between HER2-low and HER2-zero breast cancers.Methods: Comprehensive genomic and immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on FFPE samples from 129 patients with advanced HER2-negative (immunohistochemistry (IHC) 0, 1+ or 2+ with negative ERBB2 amplification by in-situ hybridization) breast cancer. Both estrogen receptor (ER) and HER2 statuses were obtained from available pathology reports. mRNA expressions of immune biomarkers, except for PD-L1 IHC and TMB, were derived from RNA-seq. Statistical comparisons were performed using the Kruskal–Wallis or Wilcoxon Rank-Sum test or the two-sample test for equality of proportions with continuity correction (p≤ 0.05 for significance). Survival differences were calculated using Kaplan-Meier analysis (p≤ 0.05 for significance).Results: There were no significant differences in mRNA expressions of immune-related genes between HER2-low and HER2-zero breast cancers. However, HER2-low breast cancers were associated with a higher proportion of ER-positivity. When ER was analyzed along with HER2, we observed a significantly higher tumor immunogenic signature (TIGS) expression in HER2-zero/ER-negative tumors than in HER2-low/ER-positive tumors (p=0.0088). Similarly, lower expression of PD-L1 and T cell immunoglobulin and ITIM domain (TIGIT) mRNA was observed in HER2-low/ER-positive tumors when compared to HER2-zero/ER-negative tumors (p=0.014 and 0.012, respectively). Patients with HER2-low tumors had a longer median OS than those with HER2-zero tumors (94 months vs 42 months, p=0.0044).Conclusion: Patients with HER2-low breast cancer have longer survivals yet display no differences in immune-related gene expression when compared to those with HER2-zero cancers. The differences in survival can be attributed to the higher rate of ER-positivity seen in HER2-low breast cancers, compared to HER2-zero tumors.Keywords: HER2-low breast cancer, estrogen receptor, tumor immune microenvironment, immune checkpoint biomarkers, gene expression profiling, immune profiling

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Songbiao Zhang,1 Jiawen Huang,1 Huilin Wang1,2 1School of Business, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 2Moray House School of Education and Sport, The University of Edinburgh, Edinburgh, Scotland, UKCorrespondence: Huilin Wang, Moray House School of Education and Sport, The University of Edinburgh, Edinburgh, Scotland, EH8 8AQ, UK, Email Huilin.Wang@ed.ac.ukIntroduction: The lack of physical exercise is a global health concern, particularly affecting women. However, there is limited research on factors influencing women’s sports participation. Recent studies on increasing women’s physical activity levels differ in methodologies and conclusions. Motivation, as the cornerstone of most human behaviors, has important effects on female motor participation. Self-Determination Theory (SDT) is an important method to study human behavioral motivation and supported by empirical evidence. In the field of women’s sports, the SDT is also widely used. This review explores the impact of SDT-related factors on women’s sports participation, considering age variations. It aims to guide future empirical research and promote PA across demographics.Methods: This review, by searching the existing empirical literature in Web of Science, Google Scholar, Elsevier ScienceDirect, CNKI, obtained 32 independent studies, conducted a meta-analysis after coding them, considering 11 influencing factors from the integration of SDT and Basic Psychological Needs Theory.Results/Conclusion: The study found a significant positive correlation between autonomous motivation and women’s sports participation, with identified regulation having the strongest influence. Controlled motivation showed no significant impact on women’s exercise, while amotivation had an inhibitory effect. Enhancing women’s perception of autonomy, competence, and relatedness significantly promotes sports participation. Age differences were observed in the relationship between autonomous motivation, basic psychological needs, and sports participation, with the strongest effects on women aged 25– 40, while the impact was relatively weaker in older women. The correlation between basic psychological needs and female sports participation also has a significant age difference. Thus, different measures should be taken to improve exercise participation in women of different age groups.Keywords: sports participation, self-determination theory, women, meta-analysis

Qianqian Li,1,&ast; Yujie Liu,2,&ast; Zulun Zhang,1 Sheng Zhang,1 Xiao Ding,2 Faming Zhang1,3 1Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 2Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3National Clinical Research Center for Digestive Diseases, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faming Zhang, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing, 210011, People’s Republic of China, Email fzhang@njmu.edu.cnPurpose: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term.Patients and Methods: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT.Results: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05).Conclusion: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients.Clinical Trial Registration: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.Keywords: faecal microbiota transplantation, transendoscopic enteral tubing, sleep disorder, Crohn’s disease, ulcerative colitis, inflammatory bowel disease

Yue Xu,1,&ast; Shuhong Zhang,1,&ast; Ping Wang,1,&ast; Yuanyuan Chen,1 Yazhan Mao,2 Xina Yuan,3 Yinyi Li,4 Mingming Li,1 Li Sheng,1 Xiaoqian Li,1 Na Gao1 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Respiratory, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 3College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Gao; Xiaoqian Li, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China, Tel +86 18515165409, Email gaona301s@163.com; 41705763@qq.comObjective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population.Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality.Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062– 115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086– 1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282– 41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558– 45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029– 28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P< 0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P< 0.05) but not of all-cause mortality in this cohort.Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.Keywords: frailty, hypertension, older people, observational study, prediction model

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Juan Li,1,&ast; Ting Zhou,1,&ast; Pei Wang,1,&ast; Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,&ast; Hongxing Wang1,&ast; 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Panpan Xu,1– 3 Yu Cao,1– 3 Ruiqing Ren,1– 3 Shuai Zhang,1– 3 Cheng Zhang,1– 3 Panpan Hao,1– 3 Meng Zhang1– 3 1State Key Laboratory for Innovation and Transformation of Luobing Theory, Jinan, People’s Republic of China; 2Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Meng Zhang; Panpan Hao, Department of Cardiology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhangmeng@sdu.edu.cn; panda.how@sdu.edu.cnPurpose: The systemic inflammation response index (SIRI) and the systemic immune inflammation index (SII) are indicators that reflect the body’s overall systemic inflammatory response. Inflammation plays an important role in the pathogenesis of in-stent restenosis (ISR). The aim of this study was to investigate the predictive value of preoperative SIRI and SII for the occurrence of ISR in patients undergoing coronary stent implantation.Materials and Methods: We retrospectively analyzed the clinical, hematological, and angiographic data of 387 patients who underwent coronary angiography for recurrent angina after coronary stent implantation at Qilu Hospital of Shandong University. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff values for SIRI and SII to predict ISR. Based on the optimal cutoff values for SIRI and SII, patients were categorized into high-SIRI, low-SIRI, high-SII, and low-SII groups. Multivariate logistic regression models were constructed to assess the predictive value of SIRI and SII for ISR > 50% and ISR > 70%.Results: This study included a total of 387 patients who underwent coronary angiography and follow-up at Qilu Hospital of Shandong University. Patients in the high-SIRI group had a higher incidence of ISR than those in the low-SIRI group (ISR > 50%: 44.8% vs 30.7%, p = 0.018; ISR > 70%: 41.5% vs 4.5%, p < 0.001). In addition, ISR occurred more frequently in patients with a higher SII than in patients with a lower SII (ISR > 50%: 52.6% vs 35.7%, p = 0.001; ISR > 70%: 51.9% vs 23%, p < 0.001). In multivariate logistic regression analysis, SIRI and SII were found to be independent predictive factors for ISR, both as continuous and categorical variables. In the ROC analysis, the optimal cutoff value for SIRI was set at 0.54 (sensitivity: 84.5%, specificity: 27%), and the optimal cutoff value for SII was set at 545.29 (sensitivity: 44.1%, specificity: 71.7%).Conclusion: Elevated preoperative SIRI and SII values help predict ISR and may serve as a useful screening tool to perform interventional procedures based on the patient’s risk of ISR after stent implantation.Keywords: SIRI, SII, in-stent restenosis, percutaneous coronary intervention

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

Shuping Zhang,1,&ast; Yamei Ma,1,&ast; Xiu Zang,2 Hao Heng,2 Xuekui Liu,2 Gangshan Peng,3 Ran Liu,3 Jun Liang,1,2,&ast; Houfa Geng1,2,&ast; 1Graduate School, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3The Affiliated Xuzhou Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houfa Geng; Jun Liang, Email genghoufa@xzhmu.edu.cn; liangjun@xzhmu.edu.cnAbstract: Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.Keywords: 17q12 microdeletion syndrome, HNF-1β gene, special-type diabetes, MODY5, polycystic kidneys, liver damage

Jun Zhang,1 Shengjun Zhang,2 Minli Liu,1 Zhe Yang,1 Rong Huang1 1Department of Medical College of Yan’an University, Yan ‘an, People’s Republic of China; 2Department of General Surgery, Affiliated Hospital of Yan ‘an University, Yan ‘an, People’s Republic of ChinaCorrespondence: Shengjun Zhang; Minli Liu, Email zsj@yau.edu.cn; lml@yau.edu.cnAbstract: In recent years, more and more researches on cell death mode in breast cancer, including apoptosis, ferroptosis, etc. Ferroptosisis a regulated form of cell death characterized by iron-dependent accumulation of lipid peroxidation to lethal levels, and numerous studies have shown that ferroptosis is closely associated with tumor cells. Breast cancer is one of the malignant tumors with the highest incidence in women, and TNBC accounts for about 15– 20% of all types of breast cancer. Due to the poor prognosis, strong aggressiveness, high drug resistance and lack of molecular targeting characteristics of TNBC, the treatment of TNBC faces many difficulties and great challenges. A large number of studies have shown that ferroptosis plays an important role in the occurrence and development of TNBC, tumor diagnosis, treatment and prognosis, among which the main mechanisms inducing ferroptosis include oxidative stress pathway, iron metabolism pathway and lipid metabolism pathway. Since TNBC is highly sensitive to oxidative stress pathways, intracellular GSH reduces reactive oxygen species under the action of GSH peroxidase (GPX), and when intracellular lipid peroxidase (LPO) accumulates to a certain level, ferroptosis will be induced, thus achieving the purpose of killing TNBC cells. In addition, lipid metabolism is highly consistent with the high lipid level of TNBC tumor cells. As a new therapeutic method, nanotechnology has added security to the treatment of cancer with its high safety and excellent biocompatibility. Therefore, the combination of nanotechnology with iron-based radiotherapy, chemotherapy, targeting and immunization has great research value for the treatment of TNBC In addition, the novel idea of treating TNBC with ethnopharmacology combined with ferroptosis is also involved. This article reviews the mechanism of ferroptosis and the recent research on the treatment prospects of TNBC based on ferroptosis and nanotechnology, hoping to provide references for the treatment of diseases based on ferroptosis.Keywords: triple-negative breast cancer, ferroptosis, nanotechnology, treatment

Shanming Zhang, Tianrou Chang, Zhihua Li College of Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of ChinaCorrespondence: Tianrou Chang, College of Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China, Email changtiro0818@163.comPurpose: To deeply explore the relationship between parental psychological control and negative risk-taking behaviors among Chinese college students and the mediating role of autonomy and self-control, providing a reference basis for preventing and intervening in college students’ negative risk-taking behaviors.Patients and Methods: Questionnaires was administered to 1173 college students (Mage=20.7 ± 1.32) in Hunan Province using four scales. Subsequently, we processed and analyzed the collected data using SPSS 26.0 software.Results: Parental psychological control demonstrated a significantly positive correlation with college students’ negative risk-taking behaviors. The impact of parental psychological control on college students’ negative risk-taking behaviors was mediated by self-control and the combined effect of autonomy and self-control.Conclusion: Among Chinese college students, autonomy and self-control act as a sequential mediating factor between negative risk-taking behaviors and parental psychological control. This study uncovered the underlying process by which parenting practices affected college students’ negative risk-taking behaviors. It offers empirical support for successful treatments aimed at reducing future risk-taking behaviors among college students, as well as some evidence in favor of the crucial part that parenting styles play in the development of positive adolescents.Keywords: college students, parental psychological control, negative risk-taking behaviors, autonomy, self-control

Min Lei,1,2,&ast; Zheng Jiang,1,2,&ast; Peng Xu,1,2 Zhenglin Chang,1– 3 Yuyan Zhang,4 Shike Zhang,1,2 Lingyue An,1,2,5 Shujue Li,2,3 Tao Zeng,2,3 Hans-Göran Tiselius,6 Yuhao Zhou,1,2 Guohua Zeng,2,3 Wenqi Wu1,2 1Department of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 2Guangdong Key Laboratory of Urology, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 4Guangzhou Institute of Dermatology, Guangzhou, Guangdong, 510095, People’s Republic of China; 5Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of China; 6Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, 14186, Sweden&ast;These authors contributed equally to this workCorrespondence: Wenqi Wu; Guohua Zeng, Email 2009681012@gzhmu.edu.cn; gzgyzgh@vip.sina.comBackground: The purpose of this study was to identify bacterial differences between urine cultures (UC) and stone cultures (SC) in patients with complex kidney stones and to determine any correlation with post-percutaneous nephrolithotomy Systemic Inflammatory Response Syndrome (SIRS).Methods: Perioperative data of 1055 patients with complex kidney stones treated with first-stage Percutaneous Nephrolithotomy (PCNL) from September 2016 until September 2021 were included. Preoperative mid-stream urine samples and surgically obtained stone material were subjected to bacterial culture and antibiotic sensitivity tests. Preoperatively, antibiotic usage was determined by the UC or local bacterial resistance patterns. After PCNL treatment, antibiotic selection was guided by stone bacterial culture result and clinical symptoms. The effect of different preoperative antibiotic regimens based on urine cultures and postoperative antibiotic treatment based on stone cultures were assessed.Results: Positive stone cultures (SC+) were significantly more common than positive urine cultures (UC+) (31.9% vs 20.9%, p < 0.05). Escherichia coli (E. coli) was the most common uropathogen in both urine (54.3%) and stones (43.9%). The difference was statistically significant (p < 0.05). Moreover, UC+SC-, UC-SC+, UC+SC+, and preoperative serum creatinine were independent risk factors of postoperative SIRS. The incidence of SIRS in the UC+SC+ patients with different bacteria in stones and urine (51.6%) was higher than that in other culture groups. The antibiotic resistance of E. coli inside the stone was increased when prolonged preoperative antibiotics were administered to UC+ patients.Conclusion: The bacterial spectrum and positive outcome of culture in urine and stones were significantly different. The incidence of postoperative SIRS was highest in patients with UC+SC+ but with different bacteria strains. Prolonged pre-surgical antibiotic treatment apparently induced higher drug resistance for bacteria inside the stone.Keywords: kidney stones, bacterial spectrum, antibiotic resistance, stone culture, urine culture

Xu Yang,1,&ast; Jianwei Wu,1,&ast; Longlong Fan,2 Binghua Chen,3 Shiqiang Zhang,4 Wenzhong Zheng1 1Department of Urology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Department of Urology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Urology, Pingtan Branch of Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhong Zheng, Department of Urology, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian Province, 200001, People’s Republic of China, Email wenzhong_zheng@yeah.net Shiqiang Zhang, Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 628, Zhenyuan Road, Guangming Dist, Shenzhen, 518107, People’s Republic of China, Email zhangshq55@mail.sysu.edu.cnBackground: The involvement of cytotoxic CD4+ T cells (CD4+ CTLs) and their potential role in dictating the response to immune checkpoint inhibitors (ICIs) in patients with metastatic renal cell carcinoma (mRCC) remains an unexplored area of research.Methods: Utilizing single-cell RNA sequencing, we analyzed the immunophenotype and expression patterns of CD4+ T lymphocyte subtypes in mRCC patients, followed by preliminary validation via multi-immunofluorescent staining. In addition, we obtained a comprehensive immunotherapy dataset encompassing single-cell RNA sequencing datasets and bulk RNA-seq cohorts from the European Genome-Phenome Archive and ArrayExpress database. Utilizing the CIBERSORTx deconvolution algorithms, we derived a signature score for CD4+ CTLs from the bulk-RNA-seq datasets of the CheckMate 009/025 clinical trials.Results: Single-cell analysis of CD4+ T lymphocytes in mRCC reveals several cancer-specific states, including diverse phenotypes of regulatory T cells. Remarkably, we observe that CD4+ CTLs cells constitute a substantial proportion of all CD4+ T lymphocyte sub-clusters in mRCC patients, highlighting their potential significance in the disease. Furthermore, within mRCC patients, we identify two distinct cytotoxic states of CD4+ T cells: CD4+GZMK+ T cells, which exhibit a weaker cytotoxic potential, and CD4+GZMB+ T cells, which demonstrate robust cytotoxic activity. Both regulatory T cells and CD4+ CTLs originate from proliferating CD4+ T cells within mRCC tissues. Intriguingly, our trajectory analysis indicates that the weakly cytotoxic CD4+GZMK+ T cells differentiate from their more cytotoxic CD4+GZMB+ counterparts. In comparing patients with lower CD4+ CTLs levels to those with higher CD4+ CTLs abundance in the CheckMate 009 and 25 immunotherapy cohorts, the latter group exhibited significantly improved OS and PFS probability.Conclusion: Our study underscores the pivotal role that intratumoral CD4+ CTLs may play in bolstering anti-tumor immunity, suggesting their potential as a promising biomarker for predicting response to ICIs in patients with mRCC.Keywords: single-cell analysis, granzyme K and granzyme B, cytotoxic CD4+ T cells, immune checkpoint inhibitors, renal cell carcinoma

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

Min Wang,1,&ast; Lin Yang,1,&ast; Suhan Zhang,2 Meng Wu,1 Zhenfeng Sun,3 Liu Shen,1 Xiaowei Xu,1 Liangkun Ma,2 Jiao Li1 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China; 2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Daxing District Maternal and Child Health Hospital, Beijing, 102699, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information & Library Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China, Tel +8618618461596, Email li.jiao@imicams.ac.cnBackground: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers.Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management.Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants’ knowledge, attitudes, and practices.Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the > 20 years group strongly endorsed the course.Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.Keywords: continuing education, pregnancy health, assessment, healthcare, medical education

Lin Qi,1,&ast; Yanglei Li,2,&ast; Chengqi Kong,2,&ast; Siqi Li,2 Qinyue Wang,2 Hanqin Pan,2 Shuyi Zhang,3 Xinkai Qu,2 Ming Li,1 Mingxuan Li,2,4 Kailei Shi2 1Department of Computed Tomography, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiac Care Unit, Tongren Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kailei Shi; Mingxuan Li, Email shikailei@fudan.edu.cn; 19211280015@fudan.edu.cnBackground: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (− 74.84± 6.93 HU vs − 79.04± 8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (− 78.46± 8.56HU vs − 83.13± 8.34 HU) and LCXs (− 73.83± 10.63 HU vs − 81.38± 7.88 HU) of lesion related vessel in stable angina.Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.Keywords: peri-coronary adipose tissue, neutrophil-to-lymphocyte ratio, fat attenuation index, acute myocardial infarction

Yong Liu,1 Hui Liu,2 Queqiao Bian,1 Shuhuan Zhang,1 Yanmin Guan3 1Department of Dermatology & STD, the Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 3Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yong Liu, Department of Dermatology & STD, the Third Central Hospital of Tianjin, No. 83, Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Tel +8602284112488, Email liuyongtj@163.comBackground: Herpes zoster (HZ) typically manifests in the acute phase with distinct blisters and severe neuropathic pain. Remarkably, a subset of patients initially presents with only a mild skin rash and moderate pain that gradually intensifies, following a parabolic pattern. Despite being frequently observed in clinical settings, the underlying causes of this trajectory and its potential connection with post-herpetic neuralgia (PHN) remain unclear.Methods: To investigate this phenomenon in-depth, we conducted a meticulous retrospective study involving 529 eligible HZ patients. All these patients sought medical care at the Third Central Hospital of Tianjin, China, between January 2020 and December 2023.Results: The research identified that 14.6% of the sample (77 patients) experienced pain scores aligning with a parabolic curve. This trend was significantly more prevalent in patients aged 60 and above, accounting for 90.9% of this group, and demonstrated a positive correlation with age. Moreover, 87.0% of these patients had pre-existing medical conditions, highlighting the potential role of comorbidities in influencing the pain trajectory. A concerning 45.5% of patients sought medical attention more than seven days after the onset of symptoms, a delay that could exacerbate neurological damage. Notably, among those following a parabolic pain pattern, 66.2% eventually developed PHN, a considerably higher rate compared to the broader patient population.Conclusion: We emphasize that healthcare practitioners meticulously assess patients who initially report lower pain scores for high-risk factors potentially leading to parabolic pain increases, including being over 60 years old, having comorbid conditions, and delaying medical consultation beyond seven days from symptom onset. Early implementation of supplementary pain management therapies may mitigate the risk of PHN development and enhance the quality of life for patients. This study furnishes clinicians with a deeper understanding of the variations in HZ-related pain trajectories, promising to improve treatment approaches and prognoses for HZ patients while paving the way for enriched clinical practice in the future.Keywords: parabolic pain trajectory, herpes zoster, post-herpetic neuralgia, delayed-onset pain, adjunctive analgesics, early intervention strategies

Rongping Chen,1,&ast; Jing Li,2,&ast; Danqi Chen,3,&ast; Weiheng Wen,1 Susu Zhang,1 Jitong Li,1 Yuting Ruan,1 Zhen Zhang,1 Jia Sun,1 Hong Chen1 1Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, HuaZhong University of Science and Technology Union ShenZhen Hospital, Guangdong, People’s Republic of China; 3Institute for Prevention and Control of Chronic Noncommunicable Diseases, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Chen; Jia Sun, Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email chenhong123@smu.edu.cn; sunjia@smu.edu.cnObjective: Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM.Methods: We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs. The primary outcome was assessed by change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour post-prandial blood glucose (2h-PPG). The secondary safety outcomes assessed were hypoglycemic events, serious adverse events (SAEs), cardiovascular (CV) events, and gastrointestinal (GI) events.Results: Sixty-two trials were included in the analysis. The combination of DPP4i + Met revealed a comparable mean reduction in HbA1c levels to the glinides (Gli) + Met combination (mean difference [MD]: − 0.03%, 95% CI: 0.69, − 0.65), although the difference was not statistically significant. The mean HbA1c reduction with DPP4i + Met was greater than with sulfonylureas (SU) + Met (MD: − 0.05, 95% CI: − 0.29, 0.39), thiazolidinedione (TZD) + Met (MD: − 0.69, 95% CI: − 1.39, − 0.02), and SU + TZD (MD: 0.21; 95% CI: − 1.30, 1.71), with no statistical significance. DPP4i + Met demonstrated a non-significant lower incidence of CV events in comparison to TZD + Met (RR: 1.01, 95% CI: 0.46, 2.45) and SU + Met (RR: 1.06, 95% CI: 0.61, 2.06).Conclusion: DPP4i in combination with Met was efficacious and had a well-tolerated safety profile compared with other traditional OADs. This combination can be considered as a suitable treatment option for patients with T2DM.Keywords: dipeptidyl peptidase-4 inhibitors, efficacy, safety, metformin, type 2 diabetes mellitus

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