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Wenqi Wu,1,2,* Xiaohao Hu,1,2,* Linyang Yan,3,* Zhiyin Li,4 Bo Li,5 Xinpeng Chen,6 Zexun Lin,7 Huiqiong Zeng,8 Chun Li,9 Yingqian Mo,10 Yalin Wu,3 Qingwen Wang1,2 1Department of Rheumatology and Immunology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, People’s Republic of China; 3Department of Ultrasound, Institute of Ultrasonic Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, People’s Republic of China; 4Department of Information Systems, City University of Hong Kong, Hong Kong, People’s Republic of China; 5Department of Rheumatology and Immunology, People’s Hospital of Longhua District, Shenzhen, People’s Republic of China; 6Department of Rheumatology and Immunology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, People’s Republic of China; 7Shenzhen Nanshan Medical Group HQ Taohuayuan Community Health Service Center, Shenzhen, People’s Republic of China; 8Traditional Chinese Medicine Department of Rheumatism, Women & Children Health Institute, Shenzhen, People’s Republic of China; 9Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yalin Wu; Qingwen Wang, Email yalinwu@jj.ac.kr; wangqingwen@pkuszh.comObjective: In primary healthcare, diagnosing rheumatoid arthritis (RA) is challenging due to a general lack of in-depth knowledge of RA by general practitioners (GPs) and the lack of effective tools, leading to high rates of missed diagnosis. This study focuses on a screening model for primary healthcare, aiming to improve early RA screening accuracy and efficiency at a relatively lower cost, reducing delays in GPs’ recognition of RA.Methods: We randomly selected 2106 participants from the RA group or combined control group (comprising healthy individuals and patients with non-RA rheumatic diseases) at Peking University Shenzhen Hospital as the developing cohort. Guided by experienced rheumatologists, we built a comprehensive database with 26 clinical features. Using 10 classical machine learning algorithms, we developed screening models. Evaluation metrics determined the best model. Employing multivariatelogistic regression results and the best-performing model to identify the least costly features, ensuring applicability in primary healthcare clinics. Subsequently, we retrained and validated our proposed model based on two primary healthcare validation cohorts.Results: In experiments, the algorithms achieved over 88% accuracy on training and test sets. Random Forest (RF) excelled with 96.20% (95% CI 95.39% to 97.02%) accuracy, 96.22% (95% CI 95.40% to 97.03%) specificity, 96.18% (95% CI 95.37% to 97.00%) sensitivity, and 96.20% (95% CI 95.39% to 97.02%) Areas Under Curves (AUC). A meticulous feature selection identified 11 key features for RA screening. In an external test on two primary healthcare datasets with these features, RF demonstrated an accuracy of 88.435% (95% CI 85.55% to 91.32%), sensitivity of 98.55% (95% CI 97.47% to 99.63%), specificity of 85.56% (95% CI 82.39% to 88.73%), and an AUC of 92.055% (95% CI 89.62% to 94.49%).Conclusion: The screening model excels in automating prompt identification of RA in primary healthcare, improving the early detection of RA, and reducing delays and associated costs. Our findings contribute positively and are poised to elevate prospective RA management, fostering improvements in healthcare sector responsiveness and resource efficiency.Keywords: rheumatoid arthritis, machine learning, primary health care

Linxia Wu,1– 3,* Lei Chen,1– 3,* Lijie Zhang,1,4,* Yiming Liu,1,5,* Die Ouyang,1 Wenlong Wu,5,6 Yu Lei,5,6 Ping Han,1 Huangxuan Zhao,1– 3 Chuansheng Zheng1– 3 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 2Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China; 3Hubei Provincial Clinical Research Center for Precision Radiology & Interventional Medicine, Wuhan, Hubei Province, 430022, People’s Republic of China; 4Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, People’s Republic of China; 5Department of Interventional Radiology, Auto Valley Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China; 6Department of Interventional Radiology, Jinyinhu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430048, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuansheng Zheng; Huangxuan Zhao, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430022, People’s Republic of China, Email hqzcsxh@sina.com; zhao_huangxuan@sina.comPurpose: Type II diabetes mellitus (T2DM) has been found to increase the mortality of patients with hepatocellular carcinoma (HCC). Therefore, this study aimed to establish and validate a machine learning-based explainable prediction model of prognosis in patients with HCC and T2DM undergoing transarterial chemoembolization (TACE).Patients and Methods: The prediction model was developed using data from the derivation cohort comprising patients from three medical centers, followed by external validation utilizing patient data extracted from another center. Further, five predictive models were employed to establish prognosis models for 1-, 2-, and 3-year survival, respectively. Prediction performance was assessed by the receiver operating characteristic (ROC), calibration, and decision curve analysis curves. Lastly, the SHapley Additive exPlanations (SHAP) method was used to interpret the final ML model.Results: A total of 636 patients were included. Thirteen variables were selected for the model development. The final random survival forest (RSF) model exhibited excellent performance in the internal validation cohort, with areas under the ROC curve (AUCs) of 0.824, 0.853, and 0.810 in the 1-, 2-, and 3-year survival groups, respectively. This model also demonstrated remarkable discrimination in the external validation cohort, achieving AUCs of 0.862, 0.815, and 0.798 in the 1-, 2-, and 3-year survival groups, respectively. SHAP summary plots were also created to interpret the RSF model.Conclusion: An RSF model with good predictive performance was developed by incorporating simple parameters. This prognostic prediction model may assist physicians in early clinical intervention and improve prognosis outcomes in patients with HCC and comorbid T2DM after TACE.Keywords: hepatocellular carcinoma, type II diabetes mellitus, transarterial chemoembolization, overall survival, SHapley Additive exPlanations

Dan Li,1– 3,* Qingling Li,4,* Zhen Huang,2 Wenhao Wu,2 Xinyuan Fan,2 Jing Liu,2 Ruoran Li,2 Qi Zhang,2 Xin Su1 1Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Xuzhou First People’s Hospital, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Su, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China, Email suxinjs@163.com Qi Zhang, Department of Respiratory and Critical Care Medicine, Xuzhou Central Hospital, Xuzhou, Jiangsu, 221000, People’s Republic of China, Email zhangqi1107@126.comBackground: tNGS and mNGS are valuable tools for diagnosing pathogens in lower respiratory tract infections (LRTIs), which subsequently influence treatment strategies. However, the impact of tNGS and mNGS on antimicrobial stewardship in patients with LRTIs remains unclear.Methods: Patients diagnosed with LRTIs who underwent tNGS or mNGS between June 2021 and January 2024 were included. Patients who underwent both tNGS and conventional microbiologic tests (CMTs) were grouped into the tNGS group, the others were divided into the mNGS group. Then, the diagnostic efficacy of tNGS and mNGS was compared, along with their impact on antimicrobial management and clinical outcomes.Results: 548 patients with an initial diagnosis of LRTIs who underwent tNGS or mNGS were evaluated. Finally, 321 patients were analyzed, with 117 patients in tNGS group and 204 patients in mNGS group. The overall pathogen detection rates for tNGS and mNGS were 89.74% and 89.71% (P=0.991). The distribution of detected pathogens was similar between tNGS and mNGS, with bacteria being the predominant microorganisms. The proportions of patients who underwent antimicrobial agent changes and received targeted therapy were not significantly different between tNGS and mNGS groups (P=0.270; P=0.893). Additionally, no significant differences were noted in the rates of antibiotic de-escalation, escalation, or changes in the opposite direction (all P> 0.05). The same results was observed in the proportions of patients with addition or reductions in antiviral, antifungal, and antibacterial agents (all P> 0.05). Hospital stays, improvement rate and mortality rate were also similar (all P> 0.05).Conclusion: tNGS and mNGS demonstrate comparable overall pathogen yield rates in patients with LRTIs. Furthermore, tNGS is also comparable to mNGS in terms of adjusting antimicrobial treatments and clinical outcomes, tNGS meets the clinical needs of most patients with LRTIs and can be firstly used for these patients.Keywords: tNGS, mNGS, antimicrobial management, lower respiratory tract infection

Ping Huang,* Yong Zhao,* Haiyan Wei, Wenhui Wu, Ziwen Guo, Shiyi Ma, Meng Xu, Qin Wang, Cheng Jia, Ting Xiang, Huamao Li Department of Rehabilitation Medicine, General Hospital of Central Theater Command, Wuhan, 430065, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huamao Li; Ting Xiang, Department of Rehabilitation Medicine, General Hospital of Central Theater Command, Wuhan, 430065, People’s Republic of China, Email 71831102@qq.com; 42254403@qq.comBackground: In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the potential causal connection between blood lipids and COPD.Materials and Methods: A genome-wide association study (GWAS) on COPD was conducted, encompassing a total of 112,583 European participants from the MRC-IEU. Additionally, extensive UK Biobank data pertaining to blood lipid profiles within European cohorts included measurements for low-density lipoprotein cholesterol (LDL-C) with 440,546 individuals, high-density lipoprotein cholesterol (HDL-C) with 403,943 individuals, triglycerides (TG) with 441,016 individuals, total cholesterol (TC) with 187,365 individuals, apolipoprotein A-I (apoA-I) with 393,193 individuals, and apolipoprotein B (apoB) with 439,214 individuals. Then, MR analyses were performed for lipids and COPD, respectively. The primary analytical technique employed was the inverse-variance weighted (IVW) approach, which included a 95% confidence interval (CI) to calculate the odds ratio (OR). Additionally, a sensitivity analysis was conducted to assess the dependability of the MR analysis outcomes.Results: MR analysis was primarily based on IVW, unveiled a causal link between COPD and LDL-C (OR=0.994, 95% CI (0.989, 0.999), P=0.019), TG (OR=1.005, 95% CI (1.002, 1.009), P=0.006), and apoA-I (OR=0.995, 95% CI (0.992, 0.999), P=0.008), in addition, no causal link was found with HDL-C, TC, apoB. Sensitivity analysis demonstrated the robustness of these causal relationships. However, through multivariate MR(MVMR) and multiple testing correction, LDL-C and TG had no causal effect on the outcome. ApoA-I remained a protective factor for the risk of COPD (OR=0.994, 95% CI (0.990– 0.999), P=0.008).Conclusion: Through MR analysis, this study offers evidence of a causal link between apoA-I with COPD. This further substantiates the potential role of lipid metabolism in COPD, and has significant clinical implications for the prevention and management of COPD.Keywords: lipid metabolism, COPD, Mendelian randomization analysis, apolipoprotein A-I

Hua Zong,&ast; Yaqiong Zong,&ast; Jian Li, Shaoyun Zhao, Weipeng Wu, Runhong Chen, Guoan Zhao, Zhuolun Li Department of Neurosurgery, Changzhi People’s Hospital, Changzhi, Shanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Li, Department of Neurosurgery, Changzhi People’s Hospital, Changzhi, Shanxi Province, People’s Republic of China, Email lijian958801@163.comBackground: Resolvin D2 (RvD2), which exhibits anti-inflammatory properties, is neuroprotective. This study aimed to ascertain the potential of serum RvD2 level as a prognostic predictor of moderate-to-severe traumatic brain injury (msTBI).Methods: In this prospective cohort study, serum RvD2 levels were measured in 136 patients with msTBI and 100 healthy controls. The severity scoring systems encompassed the Rotterdam computed tomography classification and Glasgow Coma Scale (GCS). Post-trauma six-month Glasgow outcome scale (GOS) was deemed an outcome indicator, with GOS scores below 4 indicating poor prognosis. Sequential univariate and multivariate analyses were used to determine the correlative factors of changeable serum RvD2 levels and the predictors of adverse prognosis.Results: Patients displayed a marked decline in serum RvD2 levels compared to controls (median, 95.2 versus 252.8 pg/mL; P< 0.001). Serum RvD2 levels were independently correlated with GCS scores (beta, 8.989; 95% confidence interval (CI), 3.678– 14.280; P=0.001) and Rotterdam scores (beta, − 14.676; 95% CI, − 25.885--3.468; P=0.011), and were independently associated with continuous GOS scores (beta, 0.004; 95% CI, 0.002– 0.007; P=0.003), ordinal GOS scores (odds ratio, 1.008; 95% CI, 1.002– 1.015; P=0.015), and poor prognosis (odds ratio, 0.991; 95% CI, 0.983– 0.999; P=0.037) at the six-month mark. A linear correlation was observed between serum RvD2 levels and the likelihood of poor prognosis (P for nonlinear = 0.090). Serum RvD2 levels exhibited strong discrimination efficiency for the probability of poor prognosis (P< 0.001), with similar ability as Rotterdam scores (P=0.337) and GCS scores (P=0.300). The integrative model encompassing serum RvD2, Rotterdam scores and GCS scores performed well using a series of statistical methods.Conclusion: A significant decrease in serum RvD2 levels after msTBI may accurately indicate trauma severity and efficiently distinguish the possibility of poor neurological outcomes in msTBI, signifying that serum RvD2 may be of clinical significance in the prognostic prediction of TBI.Keywords: resolvin 2, traumatic brain injury, prognosis, severity, biomarkers

Weifeng He,1 Huanyi Zhao,2 Weiqi Xue,1 Yuan Luo,1 Mengyuan Yan,1 Junlong Li,2 Lijin Qing,2 Wei Wu,2 Zheng Jin2 1Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, People’s Republic of China; 2First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, People’s Republic of ChinaCorrespondence: Wei Wu; Zheng Jin, Department of Cardiovascular, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16, Ji Chang Road, Baiyun, Guangzhou, 510405, People’s Republic of China, Tel +86-020-3659-6422, Email wwhrlz@163.com; zyjinzheng@163.comBackground: Qingre Huoxue Decoction (QRHX) is a classical Chinese herbal prescription widely used in clinical practice for the treatment of atherosclerosis (AS). Our previous study demonstrated its efficacy in stabilizing plaque and improving prognosis, as well as its ability to regulate macrophage polarization. This study aimed to further investigate the effects of QRHX on AS and explore the underlying mechanisms.Methods: ApoE−/− mice were fed a high-fat diet (HFD) for 8 weeks in order to establish an AS model. Oil Red O, H&E, Masson, and IHC staining were employed to assess lipid accumulation, plaque development, collagen loss and target of the aortas tissue. ELISA was employed to measure the levels of TNF-α and IL-10 in serum. Dual luciferase reporter assay was conducted to ascertain the connection between miR-26a-5p and PTGS2 in vitro. Western blot and RT-qPCR assay were conducted to assess the NF-κB signaling pathway and macrophage polarization. The effects of miR-26a-5p were tested after transfecting miR-26a-5p over-expressive lentivirus.Results: QRHX attenuated HFD-induced plaque progression and inflammation of AS model mice. BMDM-derived exosomes (BMDM-exo) increased miR-26a-5p and decreased PTGS2 expressions, inhibited the NF-κB signaling pathway and regulated macrophage polarization in vivo. These effects of BMDM-exo were further enhanced after QRHX intervention. Dual luciferase reporter assay results showed that miR-26a-5p directly binds to the 3’-UTR of PTGS2 mRNA and regulates the expression of PTGS2. The miR-26a-5p of BMDM-exo played a key role in macrophage polarization. After overexpression of miR-26a-5p, the NF-κB signaling pathway was inhibited and macrophages were converted from M1 to M2 in vitro.Conclusion: QRHX can exert anti-inflammatory and plaque-stabilizing effects through exosomal miR-26a-5p via inhibiting the PTGS2/NF-κB signaling pathway and regulating macrophage phenotype from M1 to M2 polarization in AS.Keywords: Qingre Huoxue decoction, atherosclerosis, exosomes, miR-26a-5p, macrophage polarization

Wen Wu,1,2 Yu-Pei Zhang,1,2 Xing-Guang Qu,1,2 Zhao-Hui Zhang1,2 1Departments of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 2The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443003, People’s Republic of ChinaCorrespondence: Zhao-Hui Zhang, Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China, Tel/Fax +86 0717 6481546, Email zhaohuizhang0630@163.comPurpose: The systemic inflammation response index (SIRI) has recently emerged as a novel inflammatory and prognostic marker across various diseases. However, there is limited research examining the relationship between SIRI and 90-day functional outcome in patients with acute large vessel occlusion stroke (ALVOS) undergoing mechanical thrombectomy (MT). This study aimed to investigate the potential of SIRI as an innovative, inflammation-based predictor of 90-day functional outcome.Methods: This retrospective cohort study consecutively recruited 604 Chinese patients with diagnosed ALVOS who underwent MT at the First College of Clinical Medical Science of China Three Gorges University between July 2017 and April 2023. Comprehensive data, including baseline demographic and clinical characteristics, were systematically extracted from electronic medical records. Poor functional outcome at 90 days was defined as modified Rankin Scale (mRS) score ≥ 3. We employed logistic regression models, curve fitting, sensitivity analyses, subgroup analyses, and receiver operating characteristic (ROC) curves to validate the association between SIRI and poor outcome, as well as to assess the predictive efficacy.Results: Final analysis included 604 ALVOS subjects of whom 54.3% experienced poor functional outcome at 90 days. In the multivariate analysis, after adjusting for potential confounders, SIRI remained significantly associated with an elevated risk of poor outcomes (OR 1.18, 95% CI 1.08– 1.28, P < 0.001). Nonlinear curve fitting revealed a reverse J-shaped association between SIRI and poor outcomes, with inflection points at 4.5. Subgroup analyses showed no significant interactions (all P for interaction > 0.05), However, atrial fibrillation demonstrated a significant interaction (all P for interaction = 0.001).Conclusion: SIRI shows promise as a novel prognostic marker for 90-day functional outcome in patients with ALVOS undergoing MT. The identified nonlinear relationship and inflection point may provide valuable insights for risk stratification and clinical decision-making in this specific patient population.Keywords: systemic inflammation response index (SIRI), acute large vessel occlusion stroke (ALVOS), functional outcome, mechanical thrombectomy (MT)

Xiaole Zheng,1,&ast; Min Li,2,&ast; Ruiye Huang,3 Yang Lu,4 Jiejie Lu,1 Weiwei Wu3 1Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Clinical School of Medicine, Jiangxi University of Chinese Medicine, Nan Chang, People’s Republic of China; 3Department of Plastic and Dermatological Surgery, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 4Department of Pathology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiejie Lu, Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China, Email lujiejie677@163.com Weiwei Wu, Department of Plastic and Dermatological Surgery, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China, Email vigorwu@126.comAbstract: Giant vascular eccrine spiradenoma (GVES) is a dermal adnexal neoplasm, representing a malignant variant of eccrine spiradenoma. We report a case of giant scapular vascular eccrine spiroadenomas. This case is characterized by its large size and location in a region with sparse vascular distribution, along with a favorable postoperative prognosis, which merits reporting.Keywords: giant vascular eccrine spiradenoma, scapular, surgery

Wenai Zheng,1 Ming Zhang,2 Weiwei Wu,2 Xiaozheng Tang,1 Zhaobing Pan2 1Department of Clinical Laboratory, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, 570206, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, 570206, People’s Republic of ChinaCorrespondence: Xiaozheng Tang; Zhaobing Pan, Email 415687035@qq.com; panzhaobing0108@163.comAbstract: This case study illustrates a 24-year-old Chinese man who presented with tinea capitis associated with a fungal infection. He was administered a therapeutic regimen consisting of terbinafine, ketoconazole cream, and miconazole shampoo for 2 months. However, the symptoms recurred 3 months after the treatment ended. Fungal culture and sequencing confirmed the infection of Hortaea werneckii. Drug sensitivity testing showed that the infecting strain of the patient remained sensitive to the five commonly used antifungal drugs in vitro. While most cases infected by Hortaea werneckii present with Tinea nigra, the possibility of Hortaea werneckii infection should be considered in patients with tinea capitis living in coastal cities.Keywords: fungal infection, immunofluorescent staining, sequencing, treatment

Weiquan Wu,1,&ast; Bing Zhang,1,&ast; Weiqi Wang,2 Qiujin Bu,3 Yuange Li,3 Peihua Zhang,2 Li Zeng1 1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 2Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Radiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peihua Zhang, Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China, Email zhangph@gdmu.edu.cn Li Zeng, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China, Email lzeng@must.edu.moAbstract: The incidence of chronic wounds is steadily increasing each year, yet conventional treatments for chronic wounds yield unsatisfactory results. The delayed healing of chronic wounds significantly affects patient quality of life, placing a heavy burden on patients, their families, and the healthcare system. Therefore, there is an urgent need to find new treatment methods for chronic wounds. Plant-derived exosome-like nanovesicles (PELNs) may be able to accelerate chronic wound healing. PELNs possess advantages such as good accessibility (due in part to high isolation yields), low immunogenicity, and good stability. Currently, there are limited reports regarding the role of PELNs in chronic wound healing and their associated mechanisms, highlighting their novelty and the necessity for further research. This review aims to provide an overview of PELNs, discussing isolation methods, composition, and their mechanisms of action in chronic wound healing. Finally, we summarize future opportunities and challenges related to the use of PELNs for the treatment of chronic wounds, and offer some new insights and solutions.Keywords: exosomes, exosome-like nanovesicles, plants, chronic wound healing

Wenbin Lu,1,&ast; Xinning Chang,1,&ast; Wei Wu,2– 5 Peipei Jin,1 Shengwei Lin,1 Lize Xiong,2– 5 Xiya Yu2– 5 1Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lize Xiong; Xiya Yu, Email mzkxlz@126.com; lizexiong@tongji.edu.cn; yuxiyash@163.comObjective: To explore the effect of scalp nerve block (SNB) combined with intercostal nerve block (ICNB) on quality of recovery (QoR) after deep brain stimulation (DBS) in patients with Parkinson’s disease (PD).Methods: We conducted a prospective randomized controlled trial in which 88 patients with PD were randomly assigned to undergo SNB combined with ICNB (SNB group) or not (control group) before surgery. The primary outcome was the 15-item QoR (QoR-15) score 24 h after surgery. The secondary outcomes included QoR-15 scores at 72 h and 1 month after surgery, pain-related events, recovery events in post-anesthesia care unit (PACU), duration of anesthesia and surgery, and nerve block-related adverse events.Results: The QoR-15 score at 24 h after surgery was significantly higher in SNB group than Control group: 122.0 ± 7.6 vs 113.5 ± 11.3 (P = 0.006). SNB combined with ICNB improved QoR-15 scores at 72 h (P = 0.004) but not at 1 month after surgery (P = 0.230). The SNB group was positively related to QoR-15 scores 24 h after surgery (β = 8.92; 95% CI = 4.52~13.32) after adjusting for confounding variables. The numeric rating scale pain scores at PACU discharge and at 24 h, intraoperative opioid consumption, rescue analgesic use, and the incidence of postoperative nausea and vomiting (PONV) in SNB group were significantly lower than Control group (P < 0.05).Conclusion: Preoperative SNB combined with ICNB improved QoR and analgesia after surgery, and reduced intraoperative opioid consumption and the incidence of PONV in patients with PD who underwent DBS.Keywords: deep brain stimulation, intercostal nerve block, Parkinson’s disease, quality of recovery, scalp nerve block

Xin Wu,1– 3,&ast; Xinyu Wang,3,&ast; Haiyan Zhang,3,&ast; Hang Chen,3,&ast; Haisheng He,2 Yi Lu,1,2 Zongguang Tai,1 Jianming Chen,3 Wei Wu1,2 1Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, People’s Republic of China; 2School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, People’s Republic of China; 3Shanghai Wei Er Lab, Shanghai, 201707, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, People’s Republic of China, Tel/Fax +86-21-64175590, Email wuwei@shmu.edu.cn Zongguang Tai, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, People’s Republic of China, Tel/Fax +86-36803155, Email taizongguang@126.comPurpose: The clinical use of paclitaxel (PTX) in cancer treatment is limited by its poor water solubility, significant toxicity, and adverse effects. This study aimed to propose a straightforward and efficient approach to enhance PTX loading and stability, thereby offering insights for targeted therapy against tumors.Patients and Methods: We synthesized a paclitaxel palmitate (PTX-PA) prodrug by conjugating palmitic acid (PA) to PTX and encapsulating it into liposomal vehicles using a nano delivery system. Subsequently, we investigated the in vitro and in vivo performance as well as the underlying mechanisms of PTX-PA liposomes (PTX-PA-L).Results: PTX had a remarkable antitumor effect in vivo and significantly decreased the myelosuppressive toxicity of PTX. Moreover, the introduction of PA increased the lipid solubility of PTX, forming a phospholipid bilayer as a membrane stabilizer, prolonging the circulation time of the drug and indirectly increasing the accumulation of liposomes at the tumor site. Our in vivo imaging experiments demonstrated that PTX-PA-L labeled with DiR has greater stability in vivo than blank liposomes and that PTX-PA-L can target drugs to the tumor site and efficiently release PTX to exert antitumor effects. In a mouse model, the concentration of PTX at the tumor site in the PTX-PA-L group was approximately twofold greater than that of Taxol. However, in a nude mouse model, the concentration of PTX at the tumor site in the PTX-PA-L group was only approximately 0.8-fold greater than that of Taxol. Furthermore, the originally observed favorable pharmacodynamics in normal mice were reversed following immunosuppression. This may be caused by differences in esterase distribution and immunity.Conclusion: This prodrug technology combined with liposomes is a simple and effective therapeutic strategy with promising developmental prospects in tumor-targeted therapy owing to its ability to convert PTX into a long-circulating nano drug with low toxicity, high pharmacodynamics, and good stability in vivo.Keywords: paclitaxel palmitate liposome, prodrug, membrane stabilizer, esterase metabolism, Immunity

Qian Li, Leipeng Ren, Weitong Wu, Dangze Sun, Lin Wei, Chao Ding, Peijia Luo Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of ChinaCorrespondence: Peijia Luo, Department of Thoracic Surgery, Xi’an Chest Hospital, Xi’an, Shaanxi, 710100, People’s Republic of China, Email 1171185306@qq.comBackground: To establish and validate a nomogram for predicting the culture results of Mycobacterium tuberculosis in superficial lymph nodes.Methods: The clinical data of patients with superficial lymph node tuberculosis admitted to Xi’an City Chest Hospital from November 23, 2018, to May 30, 2024, were selected and divided into a training set and a validation set according to a ratio of 7:3. Influencing factors were identified through multivariate logistic regression analyses. Using R version 4.3.2, we developed a predictive model and generated a nomogram based on this model. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curve analysis (CCA), and decision curve analysis (DCA).Results: The positive rate of superficial lymph node tuberculosis culture was 23.0% (103/446). Multivariate Logistic regression analysis showed that anti-tuberculosis treatment duration (OR=0.98, 95% CI: 0.97 ~ 0.99), initial treatment or retreatment (OR=0.12, 95% CI: 0.05 ~ 0.28), and adenosine deaminase (OR=1.12, 95% CI: 1.03 ~ 1.22) were independent factors affecting the culture results of Mycobacterium tuberculosis in superficial lymph nodes. The areas under the ROC curves were 0.86 (95% CI: 0.82– 0.91) for the training set and 0.89 (95% CI: 0.84– 0.95) for the validation set. The P values of calibration curves were 1.000 and 0.961, respectively, and the predicted values were in good agreement with the actual values. The threshold probabilities of clinical decision curves were 3%~64% and 1%~68%, respectively.Conclusion: The positive rate of Mycobacterium tuberculosis culture in superficial lymph nodes is low. The increase in retreatment patients and anti-tuberculosis treatment time are obstacle factors for Mycobacterium tuberculosis culture positivity, while an increase in adenosine deaminase is a promoting factor for Mycobacterium tuberculosis culture positivity. The nomogram model established based on these factors can be used to predict the results of Mycobacterium tuberculosis culture in superficial lymph nodes.Keywords: superficial lymph node tuberculosis, mycobacterium culture, predictive model, nomogram

Mingwan Zhou,1 Xueti Dong,2 Weige Wu,3,4 Yun Li4,5 1Psychological Assessment Center, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 2Psychological Counseling and Treatment Center, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 3Child Psychology Department, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of China; 4Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Child and Adolescent Psychology Outpatient Clinic, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, People’s Republic of ChinaCorrespondence: Yun Li, Department of Clinical Medicine, Fujian Medical University, No. 1, Xueyuan North Road, Fuzhou, Fujian Province, 350100, People’s Republic of China, Email xiaojiujiuo123@sina.comObjective: Numerous studies have shown that the mental health of middle school students is closely related to problematic mobile phone use. The purpose of this study is to investigate the network structure between the dimensions of the Middle School Students Mental Health Scale and the items of the Self-Rating Questionnaire for Adolescent Problematic Mobile Phone Use by using the network analysis, to clarify the core symptoms and bridge symptoms of the network structure, and to provide ideas and methods for intervening in the mental health and problematic mobile phone use of middle school students.Methods: A stratified cluster sampling method was used to select 1637 students from four general middle schools in Xiamen in June 2020 for the survey, and the Middle School Students Mental Health Scale (MSSMHS-60) and the Self-Rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) were used. SPSS28.0 was used for descriptive statistical analysis and R (version 4.2.1) for network analysis.Results: 1. The core symptoms of the network of middle school students’ mental health and problematic mobile phone use were “spending more time playing with the phone in order to be satisfied”, anxiety, and depression; 2. The bridge symptoms of the network of middle school students’ mental health and problematic mobile phone use were academic stress, psychological disequilibrium, and “depression without phone”.Conclusion: Reducing the time of smartphone use and relieving anxiety and depression can improve the mental health of middle school students and reduce the incidence of problematic mobile phone use; helping middle school students adjust their study pressure and improving their social support level can reduce the severity of problematic mobile phone use.Keywords: problematic mobile phone use, network analysis, middle school students, mental health

Wenxin Wu,1,&ast; Kai Chang,2,3,&ast; Liying Bai1 1School of Humanities and Social Sciences, Fuzhou University, Fuzhou, People’s Republic of China; 2Institute of Education, Xiamen University, Xiamen, People’s Republic of China; 3College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liying Bai, School of Humanities and Social Sciences, Fuzhou University, 2 Wulongjiang North Avenue, Fuzhou, 350108, People’s Republic of China, Email bxuer@fzu.edu.cnBackground: The mental health of graduate students is increasingly turning into one of the main issues in global health. Understanding the antecedents of graduate students’ mental health and finding ways to improve the situation are crucial for the students and the entire educational system.Purpose: This study explores the relationship between supervisor narcissism and graduate students’ mental health. Additionally, the study examines the mediating effects of mentorship styles (relationship-oriented and task-oriented) and the moderating role of student’s proactive personality.Methods: This study conducted a three-wave survey, with each wave administered at four-month intervals, involving 547 graduate students. They completed questionnaires on supervisor narcissism, mentorship styles, proactive personality, and mental health. SPSS 26.0 was used to test our hypotheses.Results: This study indicated that: (1) Supervisor narcissism was negatively associated with graduate students’ mental health, fully mediated by relationship-oriented and task-oriented mentorships; (2) Graduate students’ proactive personalities moderated the relationship between these mentorship styles and their mental health; (3) Graduate students’ proactive personalities moderated the indirect effect of supervisor narcissism on students’ mental health through these mentorship styles.Conclusion: This study reveals the detrimental mechanisms through which supervisor narcissism affects graduate students’ mental health. It also demonstrates that enhancing students’ proactive personalities can mitigate these adverse effects. These findings provide empirical evidence within the context of higher education. Practical implications are provided for supervisors, students, and university administrators, emphasizing the importance of effectively matching supervisors with students and promoting students’ proactive personalities. These measures are essential for improving the mental health of graduate students.Keywords: supervisor narcissism, mental health, mentorship style, proactive personality

Yang Zhao,1,2,&ast; Jialong Chen,1,2,&ast; Muran Zhou,1,2 Guo Zhang,1,2 Wenhao Wu,1,2 Zhenxing Wang,1,2 Jiaming Sun,1,2 Aimei Zhong1,2 1Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aimei Zhong; Jiaming Sun, Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-13317174169 ; +86-13986246496, Fax +86-027-85726240, Email aimei_zhong@hust.edu.cn; sunjm1592@sina.comBackground: Delayed diabetic wound healing is one of the clinical difficulties, the main reason is the limited angiogenesis ability. Deferriamine (DFO) is an iron chelating agent that can induce angiogenesis, but its application is limited due to its short half-life. Increasing the load and slow release performance of desferriamine is beneficial to accelerate diabetic wound healing.Materials and Methods: In this study, we developed collagen (Col)-graphene oxide (GO) and (1% w/w) DFO-loaded nanofiber electrospinning scaffolds (DCG) using the electrospinning technique. We tested the physicochemical properties, drug release performance, and vascularization biological function of the scaffolds, and finally evaluated the promotion of full-thickness wound healing in the diabetic rat models.Results: The results showed that DCG scaffolds have good mechanical properties and water-holding capacity and can release DFO continuously for 14 days. In vitro, the novel DCG scaffold exhibited good biocompatibility, with the up-regulation at the gene level of VEGF and its regulator HIF-1α, promoters of angiogenesis. This was verified in vivo, as the scaffold enhanced granulation tissue formation and improved neovascularization, thereby accelerating wound healing when applied to full-thickness defects on the back of diabetic rats.Conclusion: The DCG nanofiber scaffold prepared in this study has good biocompatibility and vascularization ability, and improves the microenvironment in vivo, and has a good application prospect in diabetic wound repair.Keywords: diabetic wounds, angiogenesis, desferrioxamine, graphene oxide, electrospinning, drug release

Wentao Wu,1,&ast; Fei Wen,1,&ast; Jiaxin Hu,1 Leijun Li2 1Department of Psychiatry, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, People’s Republic of China; 2Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leijun Li, Email lljzssyxl@163.comBackground: Anxiety disorders seriously impair patients’ mental health and quality of life, with limited effectiveness of current treatments. Dysregulation of activating transcription factor 4 (ATF4) is involved in various mental diseases, but the research on its potential roles in alleviating anxiety disorders remains limited.Methods: ATF4 was screened out by bioinformatic analysis and its expression was verified in vivo. Mice were treated with 21 d of chronic restraint stress to establish the anxiety mice model. The anxiolytic effect of ATF4 was assessed by a battery of behavior tests and evaluation of hippocampal tissue damage after overexpressing ATF4. Ferroptosis-related indicators were detected by enzyme-linked immunosorbent assay and Western blotting. Then the transforming growth factor beta (TGF-β) signaling pathway was predicted as the downstream regulatory pathway of ATF4 by bioinformatic methods. Western blotting was conducted to detect the protein expression level of TGF-β 1, small mothers against decapentaplegic 3 (Smad3), and phospho-Smad3 (p-Smad3).Results: ATF4 was screened out as a ferroptosis-related anxiolytic gene after bioinformatics analysis and was down-regulated in the anxiety mice model. Mice with ATF4 overexpression spent more time in the open arms in the elevated plus-maze test, appeared more frequently in the central area in the open-field test, and decreased the immobility time in the forced swimming and tail suspension tests. Hippocampal tissue damage was alleviated, ferroptosis was suppressed, and the levels of TGF-β 1 and p-Smad3/Smad3 were increased by AFT4 overexpression.Conclusion: ATF4 overexpression can repress ferroptosis to improve anxiety disorders by activating the TGF-β signaling pathway.Keywords: anxiety disorders, ATF4, ferroptosis, hippocampus, TGF-β signaling pathway

Kaijie Wang,1 Weiwei Wu,2 Yongbao Wei,3 Xianwei Cao1 1Department of Dermatology, the 1st affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Urology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People’s Republic of ChinaCorrespondence: Xianwei Cao; Yongbao Wei, Email ndyfycxw@126.com; weiyb@fjmu.edu.cnObjective: To analyze the influencing factors of male cutaneous melanoma (CM) patients dying from genitourinary diseases (GUD).Methods: We searched the surveillance, epidemiology, and end results (SEER) database and extracted data on male CM patients according to the inclusion and exclusion criteria, including male patients whose cause of death was CM (cohort A) or GUD (cohort B). Comparisons between the two cohorts were performed before and after propensity score matching (PSM). An interaction analysis between age and year of diagnosis was also conducted. Cox regression analysis were performed to find the risk factors for death from GUD.Results: Seven thousand seventy-eight CM patients were included, including 6415 (90.6%) in cohort A and 663 (9.4%) in cohort B. Compared with cohort A, cohort B patients were older (median age 74 ys. vs 65 ys.) and were more under the localized stage and had longer survival time no matter before or after PSM (all p< 0.001). The stage was an inhibitory factor for cohort B (p < 0.001). After PSM, only age and year of diagnosis were found to be cohort B’s promoting factors (p< 0.001). The interaction analysis showed that older patients diagnosed in later years (2009– 2020) had a higher risk of dying from GUD compared to those diagnosed earlier (p< 0.05). Patients with a later year of diagnosis (2009– 2020) had a lower median survival time than patients with an earlier year of diagnosis (2000– 2008) (p< 0.001). When the patient’s year of diagnosis was earlier (2000– 2008), older patients (> 75 ys.) had a higher risk of dying from GUD than younger patients (≤ 75 ys.) (p< 0.001).Conclusion: We first reported a significant interaction between age and year of diagnosis in male CM patients dying from GUD, highlighting the increased risk in older patients diagnosed more recently. We may pay attention to the possibility of dying from genitourinary diseases for CM patients.Keywords: cutaneous melanoma, genitourinary diseases, non-cancer mortality, genitourinary cancer, cohort study

Na Ren,&ast; Fengyan Ma,&ast; Mengbai Tian, Guochao Zhang, Qi Xing, Xu Zheng, Wei Wu, Yimin Qi, Mingyu Wang, Liang Zhao Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Zhao, Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email drzhaoliang@126.comAim: Patients with lung cancer often experience a high level of self-perceived burden, which significantly affects their quality of life and psychological health. Social support is closely related to the self-perceived burden, yet there is scant research on the relationship between social support, facilitation of patient involvement, and self-perceived burden. This study aims to understand the current situation of self-perceived burden in postoperative lung cancer patients and to explore the mediating role of social support between facilitation of patient involvement and self-perceived burden.Methods: A cross-sectional design was used in this study. Using a convenience sampling method, a total of 331 lung cancer patients who were hospitalized for surgical treatment at a tertiary cancer hospital in Beijing, China, from August 2022 to May 2023, were selected to participate in this survey. The survey included a self-designed sociodemographic questionnaire, the Facilitation of Patient Involvement Scale (FPIS), the Perceived Social Support Scale (PSSS), and the Self-Perceived Burden Scale (SPBS). Data were analyzed using SPSS 24.0 for statistical description and Pearson correlation analysis, while AMOS 24.0 was utilized to construct a structural equation model to examine the mediation effect.Results: The score of self-perceived burden in lung cancer patients was 26.42 ± 8.23 points. Bot facilitation of patient involvement and social support was negatively correlated with self-perceived burden (r = − 0.313, r = − 0.332, P < 0.001). Social support plays a partially mediated role in the relationship between facilitation of patient involvement and self-perceived burden, accounting for 44.3% of the total effect.Conclusion: The self-perceived burden of patients after lung cancer surgery was at a moderate level, and social support partially mediates the relationship between facilitation of patient involvement and self-perceived burden. Medical staff should encourage patient participation in their own treatment decisions and alleviate the burden associated with lung cancer and surgical treatment by enhancing their social support.Keywords: facilitation of patient involvement, self-perceived burden, social support, mediation analysis, lung cancer

Hua Liu,1,&ast; Wenxi Wu,1,&ast; Min Xu,2 Xiaoyang Ling,2 Wei Lu,2 Feng Cheng,1 Jian Wang2 1Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China; 2Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Cheng, Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, People’s Republic of China, Email chengf1215@163.com Jian Wang, Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, 215300, People’s Republic of China, Email wj458381670@126.comBackground and Aim: Traumatic brain injury (TBI) is a severe public health problem in elderly patients, and frailty is associated with higher mortality rates in older patients. This study aims to assess the prognostic value of frailty in patients with TBI.Methods: Clinical data from 348 TBI patients treated at Affiliated Kunshan Hospital of Jiangsu University and Kunshan Hospital of Traditional Chinese Medicine between December 2018 and December 2020 were retrospectively collected. Univariate and multivariate logistic regression analyses were used to determine risk factors affecting in-hospital mortality, and receiver operating characteristic (ROC) curves were plotted to assess the discriminatory power of the frailty index. Frailty was assessed using the FRAIL scale, where FRAIL stands for Fatigue, Resistance, Ambulation, Illness, and Loss of weight, with each item scored as 0 or 1.Results: Using the FRIAL questionnaire, 122 patients had low frailty and 226 had high frailty. Multivariate logistic regression analysis showed that high frailty was a risk factor for in-hospital mortality in TBI patients (P< 0.001, OR=2.012 [1.788– 2.412]). The proportion of infections occurring in the two groups was statistically different (P=0.015), with severely infected TBI patients being more likely to develop complications. The ROC curve showed an area under the curve for the FRAIL score of 0.845 [0.752– 0.938].Conclusion: Frailty is an important risk factor for in-hospital mortality in elderly TBI patients, and more attention should be paid to patients with high levels of frailty. Clinicians should consider the degree of frailty when assessing TBI and making treatment decisions.Keywords: frailty, traumatic brain injury, in-hospital mortality, prognosis

Xinling Zhao,1,2,&ast; Huijin Jie,3,&ast; Jun Wang,1 Yu Liu,4 Yilin Liu,2 Fuyi Qin,2 Qing Long,2 Xi Hou,5 Xin-Wen Zhang,6 Wenzhi Wu,7 Xiaoqin Wu,2 Jing Li,8 Yong Zeng2 1Department of Clinical Psychology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, People’s Republic of China; 2Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Haining Fourth People’s Hospital, Haining, People’s Republic of China; 4Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of Clinical Psychology, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China; 6Department of Psychiatry, Hong He Second People’s Hospital, Jian Shui, People’s Republic of China; 7Faculty of psychology, Beijing Normal University, Beijing, People’s Republic of China; 8Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li; Yong Zeng, Email lijingjingjing222@163.com; zengyong@kmmu.edu.cnBackground: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma.Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children’s Depression Inventory (CDI) and Children’s Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control.Results: The serum levels of BDNF were significantly lower (p< 0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p< 0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=− 0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value.Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.Keywords: brain-derived neurotrophic factor, p-mTOR, major depressive disorder, suicide, adolescent, childhood trauma

Zijuan Ma,1,&ast; Yunge Fan,1,&ast; Zhijun Yu,1 Wenxuan Wu,1 Xiangting Zhang,1 Huolian Li,1 Shaochen Zhao,2 Yang Li,3 Yuanyuan Li,4 Dongfang Wang,1 Fang Fan1 1Center for Studies of Psychological Application, School of Psychology, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China; 2Research Center for Guangdong-Hong Kong-Macao Policing Model Innovation, China People’s Police University, Guangzhou, People’s Republic of China; 3Department of Educational Psychology, Faculty of Education, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongfang Wang; Fang Fan, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; fangfan@scnu.edu.cnPurpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns.Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories.Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, “Difficulty in concentrating” in the persistent-high group and “Feeling tense” in the deteriorating groups.Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of “Difficulty in concentrating” and “Feeling tense” are imperative to address these specific symptoms within subpopulations.Keywords: sleep inertia, change patterns, network structures, intern nurse, shift work

Yu Qiu,1,2,&ast; Yan Chen,1,2,&ast; Haoyang Shen,1,2 Shuixin Yan,1,2 Jiadi Li,1,2 Weizhu Wu1 1The Affiliated Lihuili Hospital, Ningbo University, Ningbo, 315000, People’s Republic of China; 2Health Science Center, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhu Wu, The Affiliated Lihuili Hospital, 1111 Jiangnan Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel +86 574 13957402451, Email wuweizhu1128@163.comPurpose: This study investigated the correlation between the Naples prognostic score (NPS), clinicopathological traits, and the postoperative prognoses of patients with triple-negative breast cancer (TNBC). Based on NPS, a predictive nomogram was developed to estimate the long-term survival probabilities of patients with TNBC post-surgery.Patients and Methods: We retrospectively examined the clinical records of 223 women with TNBC treated at Ningbo Medical Center, Lihuili Hospital between January 1, 2016 and December 31, 2020. Blood tests and biochemical analyses were conducted before surgery. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and NPS were determined based on blood-related markers. A Kaplan-Meier survival analysis assessed the association between NPS, PNI, CONUT score, overall survival (OS), and breast cancer-specific survival (BCSS). Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and C index. The patients were randomly divided into the training and the validation group (6:4 ratio). A nomogram prediction model was developed and evaluated using the R Software for Statistical Computing (RMS) package.Results: NPS outperformed other scores in predicting inflammation outcomes. Patients with an elevated NPS had a poorer prognosis (P< 0.001). Lymph node ratio (LNR), surgical method, postoperative chemotherapy, and NPS independently predicted OS, whereas M stage, LNR, and NPS independently predicted BCSS outcome. The OS and BCSS predicted by the nomogram model aligned well with the actual OS and BCSS. The decision curve analysis showed significant clinical utility for the nomogram model.Conclusion: In this study, NPS was an important prognostic indicator for patients with TNBC. The nomogram prognostic model based on NPS outperformed other prognostic scores for predicting patient prognosis. The model demonstrated a clear stratification ability for patient prognosis, which emphasized the potential benefits of early intervention for high-risk patients.Plain Language Summary: In this study, we aimed to understand how the Naples prognostic score (NPS) scoring system could predict the prognosis for patients with triple-negative breast cancer (TNBC). TNBC is a type of breast cancer that can be difficult to treat. Medical records of 223 women with TNBC were retrospectively analyzed. These women had their blood tested before surgery to check for certain markers related to nutrition and inflammation. NPS was used along with other scores to determine their accuracy in predicting survival. NPS was better at predicting outcomes than the other scores. The patients with higher NPS scores tended to have poorer outcomes. We also created a visual tool called a nomogram to help doctors predict patient outcomes based on the NPS scores. NPS can be a valuable tool for doctors treating patients with TNBC because it can help them predict how well a patient might do after surgery. This information could be used to tailor treatment plans for these patients. The nomogram provides a user-friendly way for doctors to use NPS in their practice. Overall, this study showed that NPS is a powerful tool for predicting outcomes for patients with TNBC, which could lead to better treatment decisions and improved outcomes for these patients.Keywords: triple-negative breast cancer, Naples prognostic score, prognostic factor, nomogram predictive model

Jiaoquan Chen, Shanshan Ou, Weihong Wu, Hui Zou, Huaping Li, Huilan Zhu Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of ChinaCorrespondence: Huilan Zhu, Department of Dermatology, Guangzhou Dermatology Hospital, 56 Hengfu Road, Guangzhou, Guangdong, 510095, People’s Republic of China, Email zhlhuilan@126.comBackground: Although omalizumab has shown success in treating chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines, the exact mechanism of action and predictive markers of response remain unclear.Purpose: The aim of this study was to examine the correlation between baseline levels of biomarkers and clinical parameters with omalizumab response and response rate in patients with CSU.Methods: This retrospective study included 82 adult CSU patients who received omalizumab 300mg every 4 weeks for 16 weeks between January 2022 and December 2023. Treatment response was assessed using UAS7 and DLQI scores at baseline and weeks 4, 8, 12, and 16. Responders were defined as patients achieving UAS7 < 7, with early and late responders categorized based on response within or after 4 weeks, respectively. Baseline clinical features and laboratory biomarkers were compared between responders and non-responders.Results: The overall response rate was 71.95% (59/82), with 23 early responders and 36 late responders. Responders had significantly lower baseline UAS7 (median: 28 vs 35, P < 0.01), DLQI (median: 8 vs 15, P < 0.001), and IL-17 levels (median: 0.53 vs 1.26 pg/mL, P < 0.001) compared to non-responders. Baseline UAS7 > 31, DLQI > 9.5, and IL-17 > 0.775 pg/mL predicted non-response with sensitivities of 78.26%, 100%, and 78.26%, and specificities of 67.8%, 59.32%, and 72.88%, respectively. ASST positivity and comorbid allergic diseases were associated with early response (P < 0.05). Adverse events were reported in 6.09% of patients, including mild injection site reactions and transient urticaria exacerbation, not requiring treatment discontinuation.Conclusion: This study suggests that omalizumab is an effective and safe treatment option for antihistamine-refractory CSU. Baseline UAS7, DLQI, ASST status, serum total IgE levels, and IL-17 may serve as potential predictors of omalizumab response. Notably, ASST positivity and comorbid allergic diseases were associated with an early response to treatment. These findings highlight the importance of considering individual patient characteristics when predicting the likelihood and timing of response to omalizumab in CSU.Keywords: Chronic spontaneous urticaria, omalizumab, response, early responder, late responder

Lin Song,&ast; Xiaosu Yuan,&ast; Zhonghao Zhao, Peiyan Wang, Weiwei Wu, Jianxun Wang School of Basic Medicine, Qingdao University, Qingdao, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxun Wang, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of China, Tel +86 532 82991791, Email wangjx@qdu.edu.cnBackground: Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI.Methods: In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation.Results: The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function.Conclusion: Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI. Keywords: myocardial infarction, ferroptosis, efferocytosis, HMSN

Wen Wu,1,2,&ast; Yu-Pei Zhang,1,2,&ast; Yu-Meng Pan,2 Zhen-Jie He,1,2 Yan-Ping Tan,1 Ding-Deng Wang,1,2 Xing-Guang Qu,1,2 Zhao-Hui Zhang1,2 1Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 2The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhao-Hui Zhang, Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, 443003, Hubei, People’s Republic of China, Tel/Fax +86-0717-6481546, Email zhaohuizhang0630@163.comPurpose: This study aims to evaluate the predictive efficacy of the C-reactive protein/albumin ratio (CAR), a cost-effective, easily accessible, and reproducible biomarker obtained from standard blood tests, in forecasting acute kidney injury (AKI) among patients undergoing acute pancreatitis (AP). Considering that changes in the CAR are associated with AKI incidence in AP cases, this work aims to explore whether CAR can be used as the innovative, inflammation-based diagnostic marker for AKI in AP patients.Methods: The current retrospective cohort study consecutively enrolled AP patients admitted to First College of Clinical Medical Science of China Three Gorges University during the period from January 2019 to October 2023. Data were extracted systematically in electronic medical records from these hospitalized individuals, including baseline demographic and clinical characteristics. To ascertain the association of the CAR level with the development of AKI, we carried out multivariate logistic regression, adjusting for potential confounders. These confounders were initially identified through univariate regression. Furthermore, the potential effect modifiers in the relationship between CAR and AKI occurrence were explored by stratified logistic regression.Results: Totally, 1514 AP were recruited, including 257 (16.9%) with AKI. CAR was positively correlated with AKI. When adjusting for potential confounders, the AKI risk in patients in the upper CAR tertile (2.628– 22.994) increased by 83% relative to those in lower tertile (0.05– 0.289) (OR 1.83, 95% CI 1.13– 2.96, P = 0.013). The AKI risk tended to increase according to the increasing CAR tertile (P for trend = 0.013). No significant interactions were observed among subgroups based on age, sex, BMI, admission to ICU, hypertension, DM, chronic obstructive pulmonary disease, severity of AP, etiology of AP, demand for CRRT, mechanical ventilation, and blood transfusion (all P > 0.05).Conclusion: A higher CAR is significantly related to the higher AKI incidence in AP patients in the Chinese population.Keywords: acute pancreatitis, acute kidney injury, CRP/albumin ratio, cohort study

Liying Zhan,1,&ast; Zhihua Lv,2,&ast; Yunjing Zhang,3,&ast; Jingdi Chen,4 Lu Wang,1 Raojuan Huang,5 Yaqi Sun,5 Wei Wu1 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Institute of Translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Orthopedics, the Airborne Military Hospital, Wuhan, Hubei, People’s Republic of China; 5First Clinical College of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, Email weiwu2012@whu.edu.cnPurpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p< 0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.Keywords: metagenomic next-generation sequencing, cerebrospinal fluid, central nervous system infections, diagnosis

Dongrui Xu,1,&ast; Xiaoyi Yang,1,&ast; Wenjuan Wu,2 Jiankang Yang1 1School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China; 2Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiankang Yang, School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China, Email jkyang1984@126.com Wenjuan Wu, Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email wuwj1021@126.comBackground: Despite the availability of numerous therapies, the treatment of acne vulgaris remains challenging. Novel drug targets for acne vulgaris are still needed.Methods: We conducted a Mendelian randomization analysis to explore possible drug targets for acne vulgaris. We utilized summary statistics obtained from the dataset of acne vulgaris, including 399,413 individuals of European ancestry. We gathered genetic instruments for 566 plasma proteins from genome-wide association studies. In order to strengthen the findings from Mendelian randomization, various methods were employed, including bidirectional Mendelian randomization analysis, Bayesian co-localization, phenotype scanning, and single-cell analysis. These methods facilitated the identification of reverse causality, the search for reported variant-trait associations, and the determination of the cell types that is the primary source of protein. Furthermore, using the plasma proteins in the deCODE cohort, we conducted a replication of the Mendelian randomization analysis as an external validation.Results: At the significance level of Bonferroni (P < 8.83× 10− 5), a protein-acne pair was discovered through Mendelian randomization analysis. In plasma, increasing TIMP4 (OR = 1.15; 95% CI, 1.09– 1.21; P = 1.01× 10− 7) increased the risk of acne vulgaris. The absence of reverse causality was observed in the TIMP4 protein. According to Bayesian co-localization analysis, TIMP4 shared the same variant with acne vulgaris (PPH4 = 0.93). TIMP4 was replicated in deCODE cohort (OR = 1.17; 95% CI, 1.10– 1.24; P = 1.48× 10− 7). Single-cell analysis revealed that TIMP4 was predominantly detected in myeloid cells in blood, and was detected in almost all cell types in skin tissue.Conclusion: The integrative analysis revealed that the level of plasma TIMP4 has a direct influence on the risk of developing acne vulgaris. This implies that TIMP4 protein could serve as a potential target for the development of drugs aimed at treating acne vulgaris.Keywords: plasma proteome, acne vulgaris, drug target, biomarker, Mendelian randomization, TIMP4

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

Peijun Li,1,&ast; Yingqi Wang,1,&ast; Yuanyuan Cao,2 Jiacheng Shi,1 Meiling Jiang,2 Xiaoyu Han,2 Linhong Jiang,1 Yidie Bao,1 Weibing Wu,2 Xiaodan Liu1,3,4 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Liu; Weibing Wu, Email hzhp403@126.com; wwb75@126.comBackground: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.Keywords: chronic obstructive pulmonary disease, diaphragmatic atrophy, exercise training, inflammation, RhoA/ROCK signaling

Jingnan Zhao,1 Chengyu Qian,2 Youqiao Jiang,1,3 Wangrui He,1 Wenhua Wu1 1Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, 330029, People’s Republic of China; 2Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Young Scientific Research and Innovation Team, Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, Jiangxi, 330029, People’s Republic of ChinaCorrespondence: Wangrui He, Tuberculosis Control Department, Jiangxi Provincial Center for Disease Control and Prevention, No. 555, Beijing East Road, Nanchang, Jiangxi, 330029, People’s Republic of China, Email jxcdccbs@126.comPurpose: In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates.Patients and Methods: A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions.Results: About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in rpoB (57.9%), Ser315Thr in katG (74.1%), Met306Val in embB (40.0%), Lys43Arg in rpsL (75.0%), Ala90Val in gyrA (32.8%) were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%.Conclusion: MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.Keywords: Mycobacterium tuberculosis, drug resistant, whole-genome sequencing, genetic diversity, transmission dynamics

Jingliang Wu,1,&ast; Qiao Lu,1,2,&ast; Jialin Zhao,3,&ast; Wendi Wu,3 Zhihua Wang,1 Guohua Yu,4 Guixiang Tian,2 Zhiqin Gao,2 Qing Wang5 1School of Medicine, Weifang University of Science and Technology, Weifang, 262700, People’s Republic of China; 2School of Life Science and Technology, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, People’s Republic of China; 4Department of Oncology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 5Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Department of Stomatology, Weifang People’s Hospital, Weifang, 261000, People’s Republic of China, Tel +86 158 6362 6389, Email wfwq8899@163.comPurpose: Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.Methods: Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro “condition medium of fibroblasts + MCF-7” cell model and in vivo “ 4T1/NIH-3T3” co-implantation mice model were established to evaluate the anti-tumor effect of drugs.Results: The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.Conclusion: In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.Keywords: drug delivery, cancer-associated fibroblasts, glucocorticoids, combination therapy

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Shuxiu Xiao,1,&ast; Lili Lu,1,&ast; Zhiyuan Lin,2,&ast; Xinming Ye,3 Sheng Su,3 Chenlu Zhang,4 Yang You,4 Wei Li,4 Xiaowu Huang,3 Weizhong Wu,5 Yuhong Zhou1,4 1Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Liver Surgery and Transplantation, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 5Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhong Zhou; Weizhong Wu, Email zhou.yuhong@zs-hospital.sh.cn; wu.weizhong@zs-hospital.sh.cnBackground: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC.Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI.Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells.Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy. Keywords: hepatocellular carcinoma, layilin, CD8+ T cell exhaustion, prognosis

Lu Zhang,1– 3,&ast; Fei Teng,1,2,&ast; Huajie Xin,1,2 Wei Xu,1,2 Wei Wu,4 Chenguo Yao,3 Zhiqiang Wang1,2 1Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Center of Thoracic Cancer, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3The State Key Laboratory of Power Transmission Equipment and System Security and New Technology, College of Electrical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China; 4College of Biological Engineering, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhang; Zhiqiang Wang, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Email luzhang_524@aliyun.com; zhiqiangwang@21cn.comAbstract: Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms. Keywords: glioma, hydrogel nano-system, immunotherapy, tumor immune microenvironment

Wenxia Wu,1,2,&ast; Jingwei Tian,1,&ast; Lisha Xiao,1 Haochen Mai,1 Phei Er Saw,3– 5 Meng Zhang1,2 1Department of General Practice, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of General Practice, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Shanwei, Guangdong, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangzhou Key Laboratory of Medical Nanomaterials, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 5Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Phei Er Saw; Meng Zhang, Email zhangm7@mail.sysu.edu.cn; caipeie@mail.sysu.edu.cnBackground: The incidence of cancer is increasing, and cancer survivors are also growing exponentially. Cancer is defined as a new chronic disease. Nevertheless, the management of cancer in the form of chronic diseases in China is still in its infancy, without a standardized care model.Objective: This study aimed to explore the current status of management of cancer care from the patient’s perspective.Methods: This cross-sectional study was a questionnaire survey of patients diagnosed with cancer, including information of the current situation of daily medical consultation, status of comorbidity, and expectations of seeking cancer care in future. Chi-square test and logistic regression analysis were used to explore the factors influencing patients’ choice of cancer management mode.Results: A total of 200 cancer patients were included in the study. The majority (n = 150) of cancer patients chose an oncologist in a tertiary hospital for cancer care. Difficulty in registration (45%), time-consuming (34.5%), repeated examinations (34.5%) and different treatment opinions (12.0%) were the main difficulties they encountered currently during tertiary hospital visits. In community hospital, lack of trust in general practitioners (n = 33) and the necessary drugs or testing items in community hospitals (n = 47) were the main difficulties during their visits. Logistic regression analysis showed that male (OR = 2.737, 95% CI, 1.332– 5.627, p = 0.006) and elderly patients (OR = 3.186, 95% CI, 1.172– 8.661, p = 0.023) were more likely to choose general practitioners (GPs) in community hospitals. Twenty-nine (14.5%) patients hope to have an integrated multidisciplinary management in tertiary and community hospitals with the active participation of GPs for cancer care.Conclusion: Improving drug availability, equipment and quality of cancer care services can help to increase cancer patients’ recognition of community hospital. In addition, the multidisciplinary management integrated tertiary hospitals and communities with the participation of GPs is a worth exploring mode that improves the management of cancer care.Keywords: cancer care, chronic disease management, general practitioners, GPs, multidisciplinary

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

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

Yingxuan Hu,1,&ast; Junqin Ma,1,&ast; Bingmei Chen,2 Jiahui Pang,1 Wen Liang,2 Wen Wu1 1Department of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Wu; Wen Liang, Email wuwen66@163.com; liangwendoc@163.comPurpose: This study was conducted to explore the differences in functional changes in the pain matrix in patients with chronic back pain (CBP) at different stages and identify whether these brain changes were related to the pain duration.Patients and Methods: In this study, 29 healthy individuals and 54 patients with CBP were recruited. According to the pain duration, 25 patients (3 to 12 months) were divided into the CBP-S group and 29 patients (≥ 24 months) were divided into the CBP-L group. All subjects completed clinical pain-related measurement and functional magnetic resonance imaging (fMRI) scans. Moreover, the amplitude of low-frequency fluctuation (ALFF), functional connectivity (FC), and correlation analysis were conducted in this study.Results: Compared with healthy controls, patients in the CBP-L group showed significantly decreased ALFF in the left precuneus. In the FC analysis, patients in the CBP-S and CBP-L groups showed significantly decreased FC in several regions in the bilateral orbitofrontal cortices (OFC) and the left ventral posterior insula. Moreover, there were significant differences in the FC between the left hyper granular insula and the probabilistic area in OFC in pairwise group comparisons. The correlation analysis results demonstrated that pain duration was correlated with these functional brain changes, and the ANCOVA results revealed that pain intensity and pain interference scores did not affect the FC analysis results.Conclusion: There are different changes in the pain neural matrix in patients with chronic pain at different stages. Furthermore, the pain duration is related to brain functional changes.Keywords: chronic back pain, pain duration, fMRI, resting-state, pain matrix

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Wei Wu,1– 4,&ast; Wenbin Lu,5,&ast; Dongmei Hong,1– 4 Xiya Yu,1– 4 Lize Xiong1– 4 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 3Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 5Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiya Yu; Lize Xiong, Tel +86-21-55603999 ; +86-21-55603002, Fax +86-21-56660851, Email yuxiyash@163.com; mzkxlz@126.com; lizexiong@tongji.edu.cnBackground: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated.Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People’s Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan–Meier curves, Cox regression models, interaction, and stratified analyses.Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17– 3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥ 70 (HR = 2.22, CI = 1.18– 4.15) and severe cases (HR = 2.09, CI = 1.13– 3.86).Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥ 70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.Keywords: biomarkers, COVID-19, hemoglobin-albumin-lymphocyte-platelet index, mortality, Omicron BA.2

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Anping Lu,1,2,&ast; Fangyi Yu,2,&ast; Xiaohan Tan,2 Xiaohong Jin,1 Xiaohua Wang,3 Wenya Wu1 1Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China; 2School of Nursing, Medical College, Soochow University, Suzhou, 215006, People’s Republic of China; 3Division of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenya Wu, Nursing Department, The First People’s Hospital of Changshu, Changshu, 215500, People’s Republic of China, Tel +86-1386236425, Fax +86-512-52223921, Email 106313851@qq.comPurpose: Previous research has consistently shown that self-perception of aging (SPA) is an important predictor of health and longevity, while Chinese rural elderly patients with hypertension had poorer SPA. Whether it was associated with their mortality kept unknown. The objective of this study was to investigate the long-term mortality and analyze the association between SPA and this mortality in the specific context of rural elderly patients with hypertension.Patients and Methods: This study is a longitudinal investigation of the mortality in elderly patients with hypertension in rural Suzhou, China. Sociodemographic and clinical data, SPA, and six-year mortality were investigated. We used binary logistic regression and subgroup analyses to assess the effect of SPA at baseline on six-year mortality.Results: A total of 280 hypertensive patients aged 60 years and older participated in the study, of whom 21 died, with a six-year mortality rate of 7.5%. After controlling for covariates, the “Emotional representation” dimension (OR=2.824, 95% CI:1.034– 7.712) in SPA remained a risk factor for death. In subgroup analyses of the group aged 75 years and older, high scores on the “Timeline cyclical” (OR=14.125, 95% CI: 1.258– 158.593) and “Emotional representations” (OR=2.567, 95% CI:1.066– 6.182) dimensions were associated with a higher risk of death, while weekly nut intake may have mitigated the negative SPA effect on mortality.Conclusion: Poorer self-perception of aging was associated with a high risk of mortality in rural elderly patients with hypertension, while the habit of weekly nut intake might help reduce this risk in the group aged 75 years or older.Keywords: China, hypertension, mortality, rural population, self-perception

Zongwei Xue,1,&ast; Xiaoyan Zhu,2– 4,&ast; Wenqi Wu,1 Yan Zhu,5 Yuhao Xu,1 Ming Yu1 1Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Neurology, People’s Hospital of Yangzhong City, Yangzhong, Jiangsu, 212299, People’s Republic of China; 3School of Clinical Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 4Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu, 225000, People’s Republic of China; 5Department of Radiology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhao Xu; Ming Yu, Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, People’s Republic of China, Tel +86 187 9601 7221, Email xuyuh0217@163.com; yuming7251@163.comBackground: Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression.Methods: In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis. Patients with depression were divided into those with MCI group (DWM group; n=145) and those without MCI (DWOM group; n=55). Data from the DWM group and the DWOM group were used to construct a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. Another 72 patients were used to validate the accuracy of our model.Results: Compared with DWOM individuals, DWM individuals were more likely to live alone (P< 0.05), had lower baseline serum levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 22 (FGF22) (P< 0.05), and exhibited higher baseline latencies of P300, mismatch negativity (MMN), and N200 (P< 0.05). Baseline serum BDNF and FGF22 levels, along with the P300 latency, were selected to construct the regression model using logistic regression. The regression equation was , and the combination of the 3 indices yielded an area under the ROC curve (AUC) of 0.790 and a predictive accuracy of 0.806.Conclusion: The logistic regression model and ROC curves based on serum BDNF and FGF22 levels and the P300 latency could provide a more effective means to predict the occurrence of MCI in patients with depression.Keywords: depression, mild cognitive impairment, brain-derived neurotrophic factor, fibroblast growth factor 22, P300, prediction

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Yufeng Ling,1 Menglu Duan,1 Wen Lyu,1 Jie Yang,1,2 Yu Liu,1,3 Shuangshuang Ren,1,4 Wenlei Wu1,3 1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 3Department of Senior Specialist, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 4Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Wenlei Wu; Shuangshuang Ren, Tel +025-83620252 ; +025-83620215, Email wlwu@nju.edu.cn; zjndrenss@163.comIntroduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair.Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration.Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation.Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery. Keywords: anti-microbial therapy, L-lysine, electrospun membrane, osteogenic, periodontal tissue regeneration

Xiaoying Meng,1,2 Fei Li,2 Wenpei Wu,3 Juncang Wu1,2 1Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical College, Hefei, Anhui, 230011, People’s Republic of ChinaCorrespondence: Juncang Wu, Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China, Email wujuncang126@126.comPurpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction.Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained.Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p< 0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p< 0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%).Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.Keywords: ischemic stroke, carotid plaque, spectral CT, effective atomic number, iodine density values, anhydrous iodine values, electron density

Sheng Tian,1,2 Heqing Zheng,1,2 Wei Wu,1,2,&ast; Lanxiang Wu1,2,&ast; 1Department of Neurology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Institute of Neuroscience, Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu; Lanxiang Wu, Email 13807038803@163.com; 1127370500@qq.comPurpose: Previous studies have shown that pyroptosis plays a vital role in the progress of neuropathic pain (NP), but the molecular mechanisms have not been fully elucidated. The aim of this study was to identify crucial pyroptosis-related genes (PRGs) in NP.Methods: We identified pyroptosis-related differentially expressed genes (PRDEGs) in NP by machine learning analysis of the GSE24982 and GSE60670 datasets. Furthermore, these PRDEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and Friends analysis, respectively. Meanwhile, receiver operator characteristic (ROC) analysis was performed to assess the diagnostic value of PRDEGs in NP. Finally, we performed immune infiltration analysis of key PRDEGs using CIBERSORTR R package.Results: We found that 5 PRDEGs by least absolute shrinkage and selection operator (LASSO) regression and random forest and verified by RT-qPCR. GO, KEGG and GSEA revealed that these PRDEGs were mainly enriched in regulation of neuron death, IL-4 signaling, IL-23 pathway, and NF-κB pathway. ROC analysis revealed that most of the PRDEGs performed well in diagnosing NP. We also revealed transcription factors, miRNA regulatory networks and drug interaction networks of PRDEGs. For immune infiltration analysis, PRDEGs were mainly correlated with dendritic cells, monocytes and follicular T helper cells, suggested that it might be involved in the regulation of neuroimmune-related signaling.Conclusion: A total of five PRDEGs were can be employed as NP biomarkers, particularly Tlr4, Il1b and Casp8, and provide additional evidence for a vital role of pyroptosis in NP.Keywords: pyroptosis, machine learning, neuropathic pain, neuroinflammation, bioinformatic analysis

Yuan Li,1,2 Xianxu Yang,3 Jiejie Lu,1 Kai Chen,3 Weiwei Wu,3 Ming Zhang,3 Wanni Li1 1Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Wanni Li, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, 570100, Hainan, People’s Republic of China, Email liwanni1204@outlook.comAbstract: Eosinophilic pustular folliculitis (EPF) is a rare skin disease. The typical skin lesions of classic EPF are localized on the upper limbs’ face, trunk, and extensor surfaces. However, when the skin lesions initially appear on the palms and soles, it is not easy to diagnose as EPF. Here, we report a case of a male patient who presented with erythematous plaques, pustules, and crusted erosions on the hands and feet, which were misdiagnosed as eczema ten years ago. Over ten years, the patient experienced recurrent erythematous patches with bumps and itching on the face, trunk, and extremities after improving the hand and foot lesions. A histopathological biopsy was performed to establish a definitive diagnosis, revealing pustules formed by eosinophilic infiltrates within the hair follicles. The diagnosis was confirmed as eosinophilic pustular folliculitis. The patient was treated with oral indomethacin at a dosage of 75mg/day, resulting in the disappearance of the skin lesions. After a 3-month follow-up, no recurrence was observed.Keywords: eosinophilic pustular folliculitis, indomethacin