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Yingfan Chen,1,2,* Zhenhui Wu,3,* Shaodan Li,2 Qi Chen,2 Liang Wang,2 Xiaorong Qi,1 Chujiao Tian,1 Minghui Yang2 1Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Traditional Chinese Medicine, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 3College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minghui Yang, Department of Traditional Chinese Medicine, the Six Medical Center, Chinese People’s Liberation Army General Hospital, 6 Fucheng Road, Beijing, 100048, People’s Republic of China, Tel +86-10-66939651, Email ymh9651@sina.comMethods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords.Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages.Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.Keywords: Parkinson’s disease, ferroptosis, bibliometric analysis, iron accumulation, alpha-synuclein, mitochondrial dysfunction, oxidative stress, lipid peroxidation

Tao Jiang,1,2 Weijian Chen,3 Chao Lu,1,2 Jiyong Yang,3 Ziquan Zeng,1,2 Wenqiang Li,4 Hongsheng Liu,5 Nana Huang,5 Yuhui Chen,6 Wengang Liu1,2 1Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 2Department of Orthopedics, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 3The Fifth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, School of Sport and Health, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 5Guangdong Huayan Biomedical Science and Technology Center, Guangzhou, 511441, People’s Republic of China; 6Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Hengfu Road 60, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email liuwengang74@163.com Yuhui Chen, Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China, Email ah1990726@163.comBackground: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy.Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo.Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe’s remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day.Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.Keywords: Cu-HMCe nanozyme, antioxidation, antibacterial, vascularization, wound healing

Jieping Yan,1,2 Xue Zhang,3 Lili Yu,4 Meihua Ye,4 Yun Chen5 1Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, 310014, People’s Republic of China; 3Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 4Department of Pathology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 5Cancer Center, Department of Oncology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of ChinaCorrespondence: Jieping Yan, Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310014, People’s Republic of China, Tel +86 571 85893117, Email yanjieping@hmc.edu.cn Yun Chen, Department of Oncology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310014, People’s Republic of China, Tel +86 571 85893609, Email chenyun@hmc.edu.cnAbstract: Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm for which a standardized treatment approach has yet to be established. The prevailing therapeutic strategy typically involves resection followed by adjuvant chemotherapy or radiation. This case report details the long-term follow-up of a 59-year-old Chinese male diagnosed with gallbladder FDCS and liver metastases. The patient received a combination therapy of sintilimab and anlotinib, resulting in a substantial partial response (PR) lasting for a noteworthy duration of 30 months. Notably, this is the first documented instance of gallbladder FDCS with liver metastases being treated with PD-1 antibody and antiangiogenic agents as first-line therapy. These findings suggest that this treatment regimen may offer a potential therapeutic option for patients with gallbladder FDCS and liver metastases, with a duration of PR lasting up to 30 months.Keywords: gallbladder follicular dendritic cell sarcoma, long-term follow-up, PD-1 antibody, antiangiogenic agents, first-line therapy, partial response

Shuling Wang,1,2,&ast; Yuqin Chen,1– 3,&ast; Weidong Li,2,4,&ast; Chunfang Hao,1,2 Li Zhang,1,2 Weipeng Zhao,1,2 Yehui Shi,1,2 Zhongsheng Tong1,2 1Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 2Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, People’s Republic of China; 3Department of Respiratory Center, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China; 4Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yehui Shi; Zhongsheng Tong, Email shiyehui@tjmuch.com; tongzhongsheng_on@163.comBackground: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer.Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP).Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p< 0.001), liver metastasis (p< 0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels.Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.Keywords: serum HER2, advanced breast cancer, clinicopathological characteristics, therapeutic efficacy, prognosis

Mengyue Zhang,1 Xiaoxian Zhang,1 Yingrui Yang,2 Yu Weng,3 Xiaojun Chen,1 Yanyan Chen,3 Yinghui Shi3 1School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Nursing, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Nursing, The Eye Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Yanyan Chen; Yinghui Shi, The Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, 270 West Xueyuan Road, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 138 5885 5689 ; +86 138 6844 0966, Email cyy@eye.ac.cn; syh@eye.ac.cnBackground: Diabetes distress (DD) is a negative emotion related to diabetes management and a predictor of depression; it affects diabetic retinopathy (DR) patients’ quality of life and disease outcomes. The prevalence of DD was higher in patients undergoing surgery for DR. However, few studies have been conducted on DD in DR surgery patients. The present study aims to investigate the status of DD in DR surgery patients and identify factors associated with DD.Methods: Using a convenience sampling method, 210 DR surgery patients who were admitted to 2 tertiary-level hospitals in Wenzhou City (Zhejiang Province) and Zhengzhou City (Henan Province) from February to June 2023 were selected as research subjects. A questionnaire collecting demographic and disease-related information, the Diabetes Distress Scale, the Summary of Diabetes Self-Management Activities, the Family Care Index Scale, and the Social Support Rating Scale were used to collect data. Statistical analyses included descriptive statistics, t tests, ANOVAs, Pearson’s correlation analyses and stepwise multiple linear regression. This study is reported according to the STROBE guidelines.Results: In total, 156 out of 210 (74.29%) DR surgery patients experienced DD, with an average score of 2.13± 0.63. The results of the stepwise multiple regression analysis showed that residential location, employment status, self-management level, family support, and social support were significantly associated with DD. These variables accounted for 30.6% of the total variation in DD.Conclusions: DR surgery patients exhibit moderate levels of distress. Health care professionals should pay attention to DD in DR surgery patients and develop targeted interventions to improve the self-management ability of these patients, increase their family support and social support to reduce their DD levels.Keywords: diabetic retinopathy, diabetes distress, self-management, family support, social support

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Haotian Shang, Yanan Chen, Qiulu Wang, Yongliang Yang, Jingyu Zhang Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of ChinaCorrespondence: Jingyu Zhang, Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, No. 41, Hailian East Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email zhangjingyu@njmu.edu.cnPurpose: This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab.Patients and Methods: We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People’s Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted.Results: Lower LDH (OR=6.237, 95% CI: 1.625– 23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099– 0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone.Conclusion: LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.Keywords: esophageal squamous cell carcinoma, camrelizumab, immunotherapy, peripheral blood, prognostic index

Yinxi He,1 Yanxia Chen2 1Department of Orthopaedic Trauma, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Yanxia Chen, Department of Endocrinology, the Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email chenyx@hebmu.edu.cnAbstract: As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes’ underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management.Keywords: exosomes, extracellular vesicles, osteoporosis, osteoblast function, osteoclast function

Xiaoli Zhu,1 Yijun Chen,1 Mingan Zhu,2 Jinxi Hu3 1Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Mingan Zhu, Department of Medical Laboratory, Renmin Hospital, Hubei University of Medicine, No. 39 Chaoyang Middle Road, Shiyan, Hubei Province, 442000, People’s Republic of China, Tel +86 13872767288, Email 839239972@qq.com Jinxi Hu, Department of Oncological Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No. 150 Ximen Road of Linhai, Taizhou, Zhejiang Province, 317000, People’s Republic of China, Tel +86 18257689350, Email hujinxi6886@163.comBackground: Prior research has established an association between small dense low-density lipoprotein cholesterol (sdLDL-C) and dyslipidemia, serving as a significant marker for predicting cardiovascular diseases. Nevertheless, the connection between sdLDL-C and metabolic syndrome (MetS) remains unclear.Methods: This study retrospectively analyzed 23,187 individuals who underwent health checkups at Taizhou Hospital’s health management center. Here, we investigated the relationship between sdLDL-C and MetS, along with its components, utilizing Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, logistic regression, and mediation analysis.Results: The MetS group exhibited significantly higher level of sdLDL-C compared to the non-MetS group (P< 0.001). We observed a strong correlation between sdLDL-C and several key factors: TG (r = 0.711), TC (r = 0.672), LDL-C (r = 0.781), GGT (r = 0.420), and HDL-C (r = − 0.417). After adjusting for age and gender, the odds ratio (OR) (95% confidence interval [CI]) for MetS incidence in the second, third, and fourth quartiles versus the first quartile of sdLDL-C concentration were 2.264 (95% CI: 1.851, 2.770), 4.053 (95% CI: 3.350, 4.903), and 9.034 (95% CI: 7.531, 10.837). The optimal cut-off value for diagnosing MetS using sdLDL-C was determined to be 0.98 mmol/L, with an area under the ROC curve (AUC) of 0.716 (95% CI: 0.705, 0.726). Additionally, mediation analysis revealed that sdLDL-C mediated a 12.8% correlation between GGT and TG concentration.Conclusion: The sdLDL-C is correlated with MetS and it can successfully mediate the relationship between GGT and TG. Our data suggests that sdLDL-c and GGT are suitable parameters for preventing and monitoring MetS.Keywords: metabolic syndrome, small dense low-density lipoprotein cholesterol, mediation analysis, GGT

Liang Tan,1,&ast; Feilong Wang,1,&ast; Yi Huang,2 Chuhua Fu,3 Haijun Zhang,4 Jianfei Feng,5 Yincai Xu,6 Xinzhen Ye,7 Rongrui Tang,8 Yinglian Chen,9 Liansheng Mou,10 Ronghao Li,11 Jingyu Chen,1 Jishu Xian1 1Department of Neurosurgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Neurosurgery, The Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Department of Neurosurgery, Xiangyang No.1 People’s Hospital, University of Medicine, Xiangyang, Hubei, People’s Republic of China; 4Department of Neurosurgery, Kaifeng Central Hospital, Kaifeng, Henan, People’s Republic of China; 5Department of Encephalopathy, Beibei Traditional Chinese Medical Hospital, Chongqing, People’s Republic of China; 6Department of Neurosurgery, Zheng Coal General Hospital, Zhengzhou, Henan Province, People’s Republic of China; 7Department of Neurosurgery, Songshan General Hospital, Chongqing, People’s Republic of China; 8Department of Neurosurgery, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 9Zhuhai Brainlightning Research Institute, Zhuhai City, Guangdong, People’s Republic of China; 10Department of Neurosurgery, Liangping District People’s Hospital, Chongqing, People’s Republic of China; 11Department of Basic Medicine, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyu Chen; Jishu Xian, Email Cjy1_2001@Hotmail.com; 1370321419@qq.comPurpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs.Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes.Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p> 0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1– 12) vs 4(1– 8), p< 0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p< 0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death.Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients.Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.Keywords: SARS-CoV-2, intensive care unit, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury

Yunpeng Feng,1 Shifeng Qiao,1 Jie Chen,1 Xin Wen,2 Yanlei Chen,3 Xiaoyu Song,1 Jiaxin Xu,1 Xiucheng Qiao,1 Jing Yang,2 Shenshen Zhang,1 Yang Feng,1 Yu Gao4 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 3The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of ChinaCorrespondence: Yu Gao, School of Basic Medical Sciences, Jinzhou Medical University, No. 40, Section 3 Songpo Road, Jinzhou, Liaoning, 121000, People’s Republic of China, Tel +86 15904161717, Email jzykdxgy@163.comPurpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

Jiandong Yang,1 Yaoqin Lu,2 Yanggui Chen,2 Yida Wang,1 Kai Wang3 1School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 2Department of Tuberculosis Control and Prevention, Urumqi Center for Disease Control and Prevention, Urumqi, 830026, People’s Republic of China; 3State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of ChinaCorrespondence: Kai Wang, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China, Email wangkaimath@sina.comObjective: This study aims to analyze the drug resistance spectrum, genetic diversity, and transmission dynamics to provide a basis for the prevention and control of drug-resistant (DR) tuberculosis (TB) epidemics.Methods: This retrospective study is based on routine national drug resistance surveillance. The demographic, epidemiological, and clinical information on DR-TB patients from 2016 to 2021 was collected and used for phenotypic drug susceptibility testing and whole-genome sequencing.Results: It was indicated that L2.2.1 was the dominant lineage in Urumqi. The drug resistance spectrum in Urumqi was narrow, which means more drug combinations can be used for clinical treatment. Furthermore, mutations identification of drug-resistance gene katG, rpoB, embA/B, rrs, rpsL, eis, gyrA/B, folC and tryA are important for clinical drug use. However, mutations in cross-resistance genes rrs have limited guidance for clinical selection of KM, CPM and AK. Moreover, there is an increased risk of cluster transmission of DR-TB, and the difference in clustering rate among L2, L3, and L4 was not statistically significant (χ2 = 2.6410, p = 0.2670).Conclusion: In the Urumqi, DR-TB has a complex prevalence state, a narrow drug resistance spectrum, and a high clustering rate and burden of drug resistance. To reduce the burden of DR-TB, related research should be strengthened, and the development of prevention, control, and treatment strategies should be accelerated.Keywords: Mycobacterium tuberculosis, resistance, whole genome sequencing, transmission dynamics, Urumqi

Ying Chen,1 Tzu-Hsuan Liu,2 Yiwei Xia,3 Zhihao Ma4 1Sports Institute, Huaqiao University, Quanzhou, People’s Republic of China; 2School of Political Science and Public Administration, Huaqiao University, Quanzhou, People’s Republic of China; 3School of Law, Southwestern University of Finance and Economics, Chengdu, People’s Republic of China; 4Computational Communication Collaboratory, School of Journalism and Communication, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhihao Ma, Computational Communication Collaboratory, School of Journalism and Communication, Nanjing University, Room 362, Zijin Building, Nanjing University (Xianlin Campus), 163 Xianlin Road, Qixia District, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 17561538460, Email redclass@163.comBackground: This study assesses the psychometric properties of the Chinese version of the Zimbardo Time Perspective Inventory (C-ZTPI-20) in an adolescent population.Methods: The investigation encompasses a sample of 2634 middle school students from China and aims to evaluate the instrument’s reliability, structural validity, measurement invariance, criterion validity, and network structure attributes.Results: First, descriptive analysis revealed satisfactory reliabilities for four out of five C-ZTPI-20 dimensions, with Present Fatalistic (PF) exhibiting relatively low reliability. Moreover, Confirmatory Factor Analysis (CFA) supported the 5-dimensional structure across all samples and sexes, albeit with a modest Tucker-Lewis Index (TLI) for girls. Furthermore, measurement invariance analysis underscores unbiased assessment across sexes. Sex differences emerge in the Present Hedonistic (PH) dimension, where boys showed higher scores. Furthermore, criteria validity analysis revealed that Past Positive (PP) and Future (F) were positively associated with extraversion, agreeableness, conscientiousness, openness, grit, and mental health, while they were negatively associated with neuroticism. Past Negative (PN) and PF showed inverse trends, while PH perspective demonstrated complex, varied correlations with these psychological traits, underscoring the multifaceted nature of time perspectives. Finally, network analysis revealed positive inter-correlations within dimensions and significant edge differences between sexes, particularly in inter-dimension connections. Despite differing rankings, the most central and marginal items remained consistent between boys and girls in network models.Conclusion: These findings contribute to understanding the C-ZTPI-20’s effectiveness in assessing adolescent time perspectives and inform interventions promoting psychological well-being and coping strategies.Keywords: time perspective, Zimbardo Time Perspective Inventory, psychometric properties, measurement invariance, network analysis

Xin Huang, Yueying Chen, Fanglu Zhong, Bin Gui, Yugang Hu, Yuxin Guo, Qing Deng, Qing Zhou Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Qing Zhou; Qing Deng, Department of Ultrasound, Renmin Hospital of Wuhan University, 238&num; Jiefang Road, Wuhan, 430060, People’s Republic of China, Email qingzhou@whu.edu.cn; wudadq@163.comBackground: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types.Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs’ impact.Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells.Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.Keywords: Ce6, nanobubbles, ultrasound, sonodynamic therapy, immunotherapy

Daoda Qi,1,&ast; Yang Chen,1,&ast; Chengyi Peng,1 Yuan Wang,2 Zihao Liang,2 Jingjing Guo,1 Yan Gu1 1Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gu; Jingjing Guo, Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +86 25 83626297, Email guyan703@foxmail.com; guojingjing0017@126.comBackground and Objective: Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era.Methods: A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves.Results: A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3– 5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count < 400/μL, the Activities of Daily Living (ADL) score ≤ 40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤ 7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively.Conclusion: We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.Keywords: early progression, CGA, nomogram, COVID-19, omicron era

Ye Liu,1,&ast; Lifan Zhang,1– 4,&ast; Yan Chen,1,&ast; Guiren Ruan,1– 3 Yuchen Liu,1 Shi Chen,1 Lantian Xie,1 Fengying Wu,1 Xiaochun Shi,1– 3 Xiaoqing Liu1– 4 1Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Beijing, 100005, People’s Republic of China, Email shixch7722@163.com; liuxq@pumch.cnBackground: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB.Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis.Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients.Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors

Wenzhen Tang,1 Yuanxi Xie,1 Qingfeng Yan,2 Yanjuan Teng,1 Li Yu,1 Liuying Wei,3 Jinmei Li,4 Yuhui Chen,1 Xiaolin Huang,1 Shaoli Yang,1 Kui Jia1 1The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2The Sanming Second Hospital, Sanming, Fujian Province, 366099, People’s Republic of China; 3Nanning Fourth People’s Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Wanxiu District Chengnan Community Health Service Center, Wuzhou, Guangxi Zhuang Autonomous Region, 543000, People’s Republic of ChinaCorrespondence: Kui Jia, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email 1960728884@qq.comAim: To investigate the current status of experience and support of nurses as second victims and explore its related factors in nurses.Design: A sequential, explanatory, mixed-method study was applied.Methods: A total of 406 nurses from seven tertiary hospitals in China were chosen as participants between September to October 2023. The Chinese version of the Second Victim Experience and Support Questionnaire (SVEST), Somatic Complaints of Sub-health Status Questionnaire (SCSSQ) and Generalized Anxiety Disorder (GAD-7) were applied to collect quantitative data. Eight nurses were selected for a qualitative study through in-depth interviews. Through interpretive phenomenological analysis, the interview data were analysed to explore the experience and support of nurses as second victims.Results: Practice distress (15.74 ± 4.97) and psychological distress (15.48 ± 3.74) were the highest dimensions, indicating Chinese nurses experienced second victim-related practice and psychological distress. Nurses with different gender, age, education, marital status, income, working hours, professional titles, and unit types have different levels of second victim-related experience and support (p

Aiming Lv,1,2 Bian Ba Zhuo Ma,3 De Qiong,2 Da Wa Zhuo Ma,2 Pu Bu Zhuo Ma,3 Donghua Yao,4 Da Zhen,2 Chunxiu Tang,2 Bian Ba Zhuo Ma,2 Youzhi Lu,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 Tong Ding,2 Lang Ji Qu Zhen,2 Da Wa Cang,5 Meng Wu,5 Yulan Chen,5 Ye Li1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Tibet Autonomous Region, Lhasa City, TB, People’s Republic of China; 3Department of Obstetrics and Gynecology, Lhasa People’s Hospital, Lhasa, TB, 850000, People’s Republic of China; 4Department of Obstetrics and Gynecology, Nyingchi People’s Hospital, Nyingchi City, TB, People’s Republic of China; 5Department of Obstetrics and Gynecology, Tibet University Medical School, Lhasa City, TB, People’s Republic of ChinaCorrespondence: Ye Li, Department of Obstetrics and Gynecology, Beijing Hospital, National center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13611118475, Fax +86 10 85136220, Email liyewtfy@126.comPurpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions.Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children’s Hospital of the Tibet Autonomous Region and the Lhasa People’s Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study.Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564– 6.764), shortness of breath (OR = 2.853, 95% CI = 1.789– 3.154), irregular breathing (OR = 2.465, 95% CI = 1.879– 4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989– 2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05).Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.Keywords: COVID-19, pregnant women, newborn

Yimeng Geng,1,&ast; Peifen Zhang,1,&ast; Yanmeng Pan,1,&ast; Huaizhi Wang,2 Yi Chen,1 Jianbo Lai,1,3,4 Shaohua Hu1– 4 1Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Psychiatry, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, 310003, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Hu, Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder’s Management, Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China, Email dorhushaohua@zju.edu.cnPurpose: Venous thromboembolism (VTE) poses a significant threat to individuals’ health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE.Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings.Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 μg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05).Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.Keywords: asymptomatic thromboembolism, D-dimer, psychiatric disorder, risk factors

Di-Fei Duan,1,2,&ast; Min Liu,1,2,&ast; Deng-Yan Ma,1,2 Lin-Jia Yan,3 Yue-Yang Huang,1,2 Yi Chen,1,2 Wei Jiang,1,2 Xi Tang,2 An-Qi Xiong,4,5 Yun-Ying Shi2 1West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deng-Yan Ma, Email mdy5104@163.comPurpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients.Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters.Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction.Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.Keywords: diabetic kidney disease, network analysis, symptom cluster, symptom management

Jaina Razbek,1 Mayisha Daken,2 Yanggui Chen,3 Li Ma,3 Yan Zhang,1 Wanting Xu,1 Baofeng Wen,1 Junan Wang,1 Xiaomin Wang,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2Department of Epidemic Prevention, Karamay Centre for Disease Control and Prevention, Karamay, 834000, People’s Republic of China; 3Department of Prevention and Control of Tuberculosis, Urumqi Centre for Disease Control and Prevention, Urumqi, 830011, People’s Republic of ChinaCorrespondence: Mingqin Cao, Tel +86-13319912419, Email cmq66@126.comPurpose: Early recognition and treatment of latent tuberculosis infection(LTBI) is key to tuberculosis(TB) prevention. However, the emergence of LTBI is influenced by a combination of factors, of which the role of individual immune cytokines remains controversial. The aim of this study is to explore the influencing factors of LTBI and their effects with cytokines on LTBI.Patients and Methods: Close contacts of tuberculosis in Urumqi City from 2021 to 2022 were selected for the study to conduct a field survey. It used logistic regression model to analyse the influencing factors of LTBI, principal component analysis to extract a composite indicators of cytokines, and structural equation modelling to explore the direct and indirect effects of cytokines and influencing factors on LTBI.Results: LTBI infection rate of 33.3% among 288 TB close contacts. A multifactorial Logistic model showed that factors influencing LTBI included education, daily contact hours, eating animal liver, and drinking coffee (P< 0.05); After controlling for confounding factors and extracting composite indicators of cytokines using principal component analysis, CXCL5 and IFN-γ is a protective factor for LTBI(OR=0.572, P=0.047), IL-10 and TNF-α is a risk factor for LTBI(OR=2.119, P=0.010); Structural equation modelling shows drinking coffee, eating animal liver, daily contact hours, and IL-10 and TNF-α had direct effects on LTBI and educations had indirect effects on LTBI(P< 0.05).Conclusion: IL-10 and TNF-α are involved in the immune response and are directly related to LTBI. By monitoring the cytokine levels of TB close contacts and paying attention to their dietary habits and exposure, we can detect and intervene in LTBI at an early stage and control their progression to TB.Keywords: close contacts, latent tuberculosis infection, cytokines, structural equation modelling, association studies

Yulin Chen,1 Yi Zhang,2 Jianjun Wang,3 Xiong Cai,1 Junzhang Chen,1 Xiaobo Min,1 Yunjie Xu,1 Qi Qin,1 Chidan Wan1 1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Engineering Research Center of Tumor-Targeted Biochemotherapy, Wuhan, 430030, People’s Republic of China; 3Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Qi Qin; Chidan Wan, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Email qinqi8441@163.com; wcdwhxhgdwk@163.comBackground: Hepatocellular Carcinoma (HCC) poses significant challenges due to limited effective treatments and high recurrence rates. Immunotherapy, a promising approach, faces obstacles in HCC patients due to T-cell exhaustion and immunosuppression within the tumor microenvironment.Methods: Using doxorubicin-loaded tumor-derived microparticles (Dox-TMPs), the mice with H22 ascites model and subcutaneous tumors model were treated. Following the treatment, mice were re-challenged with H22 cells to compare the therapeutic effects and recurrence among different groups of mice, alongside examining the changes in the proportions of immune cells within the tumor microenvironment. Furthermore, Dox-TMPs were combined with anti-PD-1 to further validate their anti-tumor efficacy. In vitro studies using various liver cancer cell lines were conducted to verify the tumor-killing effects of Dox-TMPs. Additionally, CD8+ T cells from the abdominal cavity of tumor-free mice were co-cultured with H22 cells to confirm their specific tumor-killing abilities.Results: Dox-TMPs demonstrate effective anti-tumor effects both in vitro and in vivo. In vivo, their effectiveness primarily involves enhancing CD8+ T cell infiltration, alleviating T cell immunosuppression, and improving the immune microenvironment to combat tumors. When used in combination with anti-PD-1, their anti-tumor effects are further enhanced. Moreover, some mice treated with Dox-TMPs developed anti-tumor immunity, displaying a self-specific T-cell immune response upon re-challenged with tumor cells. This suggests that Dox-TMPs also have the potential to act as a long-term immune response against tumor recurrence, indicating their capability as a tumor vaccine.Conclusion: Dox-TMPs exhibit a dual role in liver cancer by regulating T cells within the tumor microenvironment, functioning both as an anti-tumor agent and a potential tumor vaccine. Keywords: liver cancer, drug-loaded microparticles, tumor immune microenvironment, tumor vaccine

Yan Chen,1 Dansheng Le,1 Jiaxi Xu,2 Piaopiao Jin,3 Yuhan Zhang,4 Zhengluan Liao1 1Center for Rehabilitation Medicine, Department of Psychiatry, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Psychiatry, Yiwu Central Hospital, Jin Hu, Zhejiang, People’s Republic of China; 4The Second Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhengluan Liao, Center for Rehabilitation Medicine, Department of Psychiatry, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, People’s Republic of China, Tel/Fax +86-571-87312143, Email liaozhengluan@163.comPurpose: There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD.Methods: This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines.Results: Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs.Conclusion: This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD.Keywords: late-life depression, gut microbiota, inflammation, inflammatory cytokines

Yueliang Chen,1,&ast; Yun Han,2,3,&ast; Feng Guo,1 Zhenwei Yu2,3 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Guo; Zhenwei Yu, Email 3408003@zju.edu.cn; yzw_srrsh@zju.edu.cnAbstract: Imipenem is a broad-spectrum antibiotic that has been used in treating severe infections and exhibits a time-dependent PK/PD profile. Its dose should be adjusted based on renal function. However, there is little experience with imipenem dosing in obese adolescent patients with augmented renal clearance (ARC) and history of schizophrenia. This case reported successful dosing of imipenem in an obese adolescent patient with ARC based on therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD). A 15-year-old male adolescent patient with history of schizophrenia was diagnosed with ventilator-associated pneumonia due to carbapenem-susceptible Klebsiella pneumoniae and received imipenem treatment (0.5 g every 8 hours with a 1-hour infusion). However, the exposure of imipenem was suboptimal due to ARC, and there is no available model for MIPD in this patient. Thus, we utilized prediction error to find a population pharmacokinetic model that fit this patient and ran Maximum a posteriori Bayesian estimation and Monte Carlo simulation based on screened models to predict changes in drug concentrations. The dose of imipenem was adjusted to 0.5 g every 6 hours with a 2-hour infusion, and subsequent TDM revealed that dosing adjustment was accurate and successful. Finally, the patient’s status of infection improved. This study will be beneficial to imipenem dosing in similar cases in the future, thereby improving the safety and effectiveness of imipenem or other antibiotics.Keywords: case report, imipenem, therapeutic drug monitoring, population pharmacokinetic

Meng Li, Xue Li, Yong Wu, Tianyu Zhang, Mengya Li, Ying Chen Department of Anesthesiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Ying Chen, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 6 East Zhenhua Road, Lianyungang, Jiangsu, People’s Republic of China, Email yingchen20825@163.comObjective: To investigate the correlation between the amount of sufentanil used during anesthesia and intraoperative hemodynamic fluctuation and postoperative recovery in patients undergoing cardiopulmonary bypass (CPB).Materials and Methods: A retrospective analysis was performed on 454 patients undergoing elective heart surgery under CPB. Patients were divided into two groups according to the amount of sufentanil used during anesthesia: Group L (induced sufentanil 0.4– 0.6 ug /kg, maintained sufentanil 0.01– 0.02 ug/kg/min, n = 223) and Group H (induced sufentanil 4– 6 ug/kg, maintained sufentanil 0.02– 0.03 ug/kg/min, n = 231). Propensity score matching (PSM) was used at a 1:1 nearest-neighbor ratio to compare the two groups. Intraoperative use of vasoactive drugs, spontaneous heart rebound, secondary endotracheal intubation, postoperative mechanical ventilation time, the length of stay (LOS) in ICU, postoperative LOS in hospital, postoperative in-hospital mortality were analyzed.Results: After matching, a total of 144 patients were included (72 patients in Group L, and 72 patients in Group H). Multivariate logistic regression analysis showed that the dosage of sufentanil during anesthesia was significantly correlated with the utilization rate of intraoperative vasoactive drugs (P < 0.001) and the success rate of spontaneous heart rebound (p = 0.001). The utilization rate of vasoactive drugs decreased significantly in Group H (OR, 0.062; 95% CI, 0.019– 0.200) compared to that of Group L. The success rate of spontaneous heart rebound (OR, 0.187; 95% CI, 0.071– 0.491) was higher in Group H. There were no differences on postoperative recovery outcomes between the two groups.Conclusion: On the basis of our data, the use of high-dose sufentanil is beneficial to keep the cardiovascular response of patients in a stable state, but there is no significant effect on the quality of early postoperative recovery.Keywords: sufentanil, extracorporeal circulation, cardiac anesthesia

Zhendong Zhang,1,&ast; Yonghuan Chen,2,3,&ast; Lei Zhang3,4 1School of Physical Education, Zhengzhou Sias University, Zhengzhou, People’s Republic of China; 2Department of Marine Sports, Pukyong National University, Busan, South Korea; 3School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Sports Science, Jeonbuk National University, Jeonju-si, South Korea&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Email zhanglei@zzu.edu.cnPurpose: To explore the relations among personality traits, sports commitment, and exercise behavior of Chinese college students. To test whether sports commitment plays an intermediary role in the process of personality traits affecting exercise behavior. To explore the factors that affect Chinese college students’ exercise behavior from the psychological level, to promote college students to actively participate in physical exercise.Methods: A questionnaire survey was conducted on 1200 students from 6 universities using the “Personality Trait Scale”, “Sports Commitment Scale” and “Exercise Behavior Scale”. SPSS was used to analyze the differences between genders and urban and rural areas; and correlation analysis was conducted on the personality traits, sports commitment, and exercise behaviors of college students. Finally, AMOS was used to establish a structural equation model to test the mediating role of sports commitment.Results: There are significant differences between different genders in each factor of personality traits (P< 0.05); there is no significant difference between different genders in the participation opportunities of sports commitment (P=0.734), and there are significant differences in other factors. There were significant differences in each factor of exercise behavior (P< 0.05). There were no significant differences in personality traits, sports commitment, and exercise behavior between urban and rural students (P> 0.05). There was a significant correlation among personality traits, sports commitment, and exercise behavior (P < 0.01). The direct effect of personality traits on exercise behavior was not significant (P > 0.05), but there was only the mediating effect of sports commitment.Conclusion: There is a significant correlation among Chinese college students’ personality traits, sports commitment, and exercise behavior. Sports commitment plays an intermediary role between personality traits and sports commitment. Improving the level of sports commitment can encourage Chinese college students to participate in physical exercise.Keywords: personality traits, sports commitment, exercise behavior, AMOS

Fardeen Bhimani,1,&ast; Sophie Lin,1,&ast; Maureen McEvoy,1,2 Arianna Cavalli,2 Liane Obaid,2 Yu Chen,1 Anjuli Gupta,1,2 Jessica Pastoriza,1,2 Areej Shihabi,1 Sheldon Feldman1,2 1Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA; 2Albert Einstein College of Medicine, Bronx, New York, USA&ast;These authors contributed equally to this workCorrespondence: Sheldon Feldman, Department of Surgery, Division of Breast Surgery, Montefiore Medical Center, 1250 Waters Place, 7th Floor, Hutch Tower 1, Bronx, NY, USA, Email sfeldman@montefiore.orgBackground: Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population.Methods: A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate.Results: A total of 98 patients’ data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases.Conclusion: Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.Keywords: nipple-ward, breast cancer, re-excision, nipple-ward positive breast cancer, Shave trial, positive margins

Wenhui Guo,1,&ast; Xiang Lian,2,&ast; Hong Li,2 Lushun Jiang,1 Yingsha Chen,3 Ping Shen,1 Wei Yu1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University; Xiangshan First People’s Hospital Medical and Health Group; Ningbo Fourth Hospital, Ningbo, People’s Republic of China; 3Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Shen; Wei Yu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel/Fax +86 571 87236421, Email shenping123451@126.com; wyu@zju.edu.cnObjective: To evaluate the characteristics of immunocytes and cytokines associated with bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: Patients with BSIs K. pneumoniae (BSIs-Kpn) were enrolled in our hospital between 2015 and 2022. Whole blood and serum samples were collected on the first day after diagnosis. Immunocytes and cytokines profiles were assessed using multicolor flow cytometry and multiplex immunoassays, respectively. The test cytokines included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A.Results: A total of 313 patients had BSIs-Kpn, including 145 with CRKP, 43 with extended-spectrum β-lactamases (ESBL) producing Kpn (ESBL-Kpn) and 125 with non-CRKP or non-ESBL-Kpn (susceptible Kpn, S-Kpn). Absolute number of leukomonocyte (CD45+) in CRKP, ESBL-Kpn and S-Kpn were 280.0 (138.0– 523.0) cells/μL, 354.5 (150.3– 737.3) cells/μL, and 637.0 (245.0– 996.5) cells/μL, respectively. Compared with S-Kpn group, the absolute numbers of leukomonocyte (including T lymphocytes, B lymphocytes and natural killer cells) in patients with CRKP were significantly lower than that in patients with S-Kpn (P

Jingsong Luo,1,2 Yuxin Chen,2 Yanmin Tao,1 Yaxin Xu,3 Kexin Yu,2 Ranran Liu,2 Yuchen Jiang,2 Cichong Cai,2 Yiyang Mao,2 Jingyi Li,2 Ziyi Yang,2 Tingting Deng1 1School of Nursing, The Chengdu University of Traditional Chinese Medicine, Sichuan, 610000, People’s Republic of China; 2Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3School of Nursing, Tongji University, Shanghai, 200000, People’s Republic of ChinaCorrespondence: Tingting Deng, School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email dengtingting999@163.comBackground: There is substantial evidence from previous studies that abnormalities in sleep parameters associated with depression are demonstrated in almost all stages of sleep architecture. Patients with symptoms of sleep-wake disorders have a much higher risk of developing major depressive disorders (MDD) compared to those without.Objective: The aim of the present study is to establish and compare the performance of different machine learning models based on sleep-wake disorder symptoms data and to select the optimal model to interpret the importance of sleep-wake disorder symptoms to predict MDD occurrence in adolescents.Methods: We derived data for this work from 2020 to 2021 Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide Phase I Study from National Sleep Research Resource. Using demographic and sleep-wake disorder symptoms data as predictors and the occurrence of MDD measured base on the center for epidemiologic studies depression scale as an outcome, the following six machine learning predictive models were developed: eXtreme Gradient Boosting model (XGBoost), Light Gradient Boosting mode, AdaBoost, Gaussian Naïve Bayes, Complement Naïve Bayes, and multilayer perceptron. The models’ performance was assessed using the AUC and other metrics, and the final model’s predictor importance ranking was explained.Results: XGBoost is the optimal predictive model in comprehensive performance with the AUC of 0.804 in the test set. All sleep-wake disorder symptoms were significantly positively correlated with the occurrence of adolescent MDD. The insomnia severity was the most important predictor compared with the other predictors in this study.Conclusion: This machine learning predictive model based on sleep-wake disorder symptoms can help to raise the awareness of risk of symptoms between sleep-wake disorders and MDD in adolescents and improve primary care and prevention.Keywords: adolescent major depressive disorder, sleep-wake disorders symptom, insomnia, obstruct sleep apnea, machine learning prediction model, xgboost

Xiaobo Li,1,2 Chen Yu,1 Xuewei Liu,3 Yejia Chen,1 Yutian Wang,1 Hongbin Liang,1 ShiFeng Qiu,1 Li Lei,1 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Cardiology, Xiangdong Hospital, Hunan Normal University, Liling, Hunan, People’s Republic of China; 3The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Dongguan, Guangdong, People’s Republic of ChinaCorrespondence: Jiancheng Xiu, Tel +8613903064940, Email xiujch@163.comObjective: To evaluate the prognostic value of the systemic immune-inflammatory index (SII) for predicting in-hospital major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) and establish a relevant nomogram.Methods: This study included 954 AMI patients. We examined three inflammatory factors (SII, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR)) to see which one predicts in-hospital MACEs better. The predictors were subsequently screened using bidirectional stepwise regression method, and a MACE nomogram was constructed via logistic regression analysis. The predictive value of the model was evaluated using the area under the curve (AUC), sensitivity and specificity. In addition, the clinical utility of the nomogram was evaluated using decision curve analysis. We also compared the nomogram with the Global Registry of Acute Coronary Events (GRACE) scoring system.Results: 334 (35.0%) patients had MACEs. The SII (AUC =0.684) had a greater predictive value for in-hospital MACEs in AMI patients than the PLR (AUC =0.597, P< 0.001) or NLR (AUC=0.654, P=0.01). The area under the curve (AUC) of the SII-based multivariable model for predicting MACEs, which was based on the SII, Killip classification, left ventricular ejection fraction, age, urea nitrogen (BUN) concentration and electrocardiogram-based diagnosis, was 0.862 (95% CI: 0.833– 0.891). Decision curve and calibration curve analysis revealed that SII-based multivariable model demonstrated a good fit and calibration and provided positive net benefits than the model without SII. The predictive value of the SII-based multivariable model was greater than that of the GRACE scoring system (P< 0.001).Conclusion: SII is a promising, reliable biomarker for identifying AMI patients at high risk of in-hospital MACEs, and SII-based multivariable model may serve as a quick and easy tool to identify these patients.Keywords: systemic immune-inflammatory index, major adverse cardiovascular events, inflammation, acute myocardial infarction

Donghao Wang,1,&ast; Yating Chen,1,&ast; Yutong Ding,1,&ast; Yongkang Tang,1,&ast; Xiaofen Su,1,&ast; Shiwei Li,1 Haojie Zhang,1,2 Yanyan Zhou,1 Zhiyang Zhuang,1 Qiming Gan,1 Jingcun Wang,1 Yuting Zhang,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China, Tel +86-13600460056, Email nfzhanggird@163.comBackground: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP).Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points.Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively.Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.Keywords: obstructive sleep apnea, metabolic syndrome, cardiometabolic index, lipid accumulation products, screening model

Wenying Yi,1,2 Haibo Wu,1,2 Weibin Fu,1,2 Huimei Feng,1,2 Jie Huang,1,2 Haijing Li,1,2 Zhen Song,1,2 Yuwei Chen,1,2 Yingjun Zheng,1,2 Shenglin She1,2 1Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shenglin She, Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou MedicalUniversity, No. 36 Mingxin Road, Liwan District, Guangzhou, People’s Republic of China, Tel +86-13825154669, Fax +86-20-82068107, Email shenglinshe@gzhmu.edu.cnBackground: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China.Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University.Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients.Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.Keywords: schizophrenia, NAFLD, non-obese, obese, risk factors, China

Xiuqing Yuan,1,&ast; Tiantian Xin,1,&ast; Huanhuan Yu,1 Jian Huang,2 Yaohan Xu,1 Caixin Ou,1 Yongfeng Chen1 1Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Dermatology, Guangdong College of Clinical Dermatology, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongfeng Chen, Dermatology Hospital of Southern Medical University, No. 2, LuJing Road, Guangzhou, Guangdong Province, 510091, People’s Republic of China, Tel +86 13802920269, Email gdcyf@163.comPurpose: Guselkumab is a highly effective biologic agent for treating psoriasis. This study aimed to explore potential transcription factors involved in psoriasis pathogenesis and response to guselkumab treatment, aiming to provide new therapeutic strategies for psoriasis.Patients and Methods: We analyzed gene expression and single-cell RNA-seq data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) that upregulated in psoriasis and downregulated after guselkumab treatment were subjected to enrichment analyses. Single-cell regulatory network inference and clustering (SENIC) and regulon module analyses identified different regulon activities between the lesion and non-lesion skin of psoriasis. Cell-cell communication analysis revealed interactions among specific cell clusters. Transcription factor (TF) regulons were identified from the guselkumab-specific regulon network. Gene set enrichment analysis (GSEA) confirmed the IRF7 regulon in the validation cohort. Finally, the expression level of IRF7 was identified in plaque psoriasis before and after 12 weeks of guselkumab therapy by immunohistochemical experiment.Results: 799 DEGs were downregulated after guselkumab treatment. Enrichment analyses highlighted the interleukin-17 (IL-17) pathway in this gene set. The M2 module exhibited the primary difference in regulon activity. Strong cell-cell interactions were observed between keratinocytes and immune cells. IRF7 regulon had significant roles in psoriasis and treatment response, as validated by GSEA analysis using the IL-17 signaling pathway as a reference. The immunohistochemical analysis unveiled substantial differences in the expression levels of IRF7 in psoriatic skin samples before and after 12 weeks of guselkumab treatment.Conclusion: IRF7 may be the key player in psoriasis pathogenesis and the therapeutic process involving guselkumab. Targeting IRF7 might offer new therapeutic strategies for psoriasis.Keywords: guselkumab, plaque psoriasis, IL-23/IL-17 signaling pathway, SENIC analysis, TF regulon

Yiyang Li,1,&ast; Jiali Chen,1,&ast; Xingping Quan,1 Ying Chen,2 Yan Han,1 Jinfen Chen,1 Li Yang,1 Youhua Xu,3 Xu Shen,4 Ruibing Wang,1,5 Yonghua Zhao1,5 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, People’s Republic of China; 4Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghua Zhao, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China, Tel +853-88224877, Fax +853-28841358, Email yonghuazhao@um.edu.moBackground: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB integrity post-stroke; however, the definite mechanisms remain ambiguous. In the present study, we investigated the curative effects and the mechanisms of EVs derived from bone marrow mesenchymal stem cells and brain endothelial cells (BMSC-EVs and BEC-EVs) on BBB integrity after acute IS.Methods: EVs were isolated from BMSCs and BECs, and we investigated the therapeutic effect in vitro oxygen-glucose deprivation (OGD) insulted BECs model and in vivo rat middle cerebral artery occlusion (MCAo) model. The cell monolayer leakage, tight junction expression, and metalloproteinase (MMP) activity were evaluated, and rat brain infarct volume and neurological function were also analyzed.Results: The administration of two kinds of EVs not only enhanced ZO-1 and Occludin expressions but also reduced the permeability and the activity of MMP-2/9 in OGD-insulted BECs. The amelioration of the cerebral infarction, BBB leakage, neurological function deficits, and the increasing ZO-1 and Occludin levels, as well as MMP activity inhibition was observed in MCAo rats. Additionally, the increased levels of Caveolin-1, CD147, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor A (VEGFA) in isolated brain microvessels were downregulated after EVs treatment. In vitro, the employment of Caveolin-1 and CD147 siRNA partly suppressed the expressions of VEGFR2, VEGFA and MMP-2/9 activity and reduced the leakage of OGD insulted BECs and enhanced ZO-1 and Occludin expressions.Conclusion: Our study firstly demonstrates that BEC and BMSC-EVs administrations maintain BBB integrity via the suppression of Caveolin-1/CD147/VEGFR2/MMP pathway after IS, and the efficacy of BMSC-EVs is superior to that of BEC-EVs. Keywords: extracellular vesicles, ischemic stroke, Caveolin-1, CD147, matrix metalloproteinase, VEGFR2, blood-brain barrier

Yinfeng Chen,&ast; Xiaying Wang,&ast; Jie Min, Jie Zheng, Xuanli Tang, Xiaoling Zhu, Dongrong Yu, De Jin Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongrong Yu; De Jin, Department of Nephrology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of China, Email yudr68@163.com; 826901274@qq.comPurpose: This study investigated the mechanism of TSF in treating DN through network pharmacology, molecular docking, and experimental validation.Methods: To identify critical active ingredients, targets, and DN genes in TSF, multiple databases were utilized for screening purposes. The drug-compound-target network was constructed using Cytoscape 3.9.1 software for network topological analysis. The protein interaction relationship was analyzed using the String database platform. Metascape database conducted enrichment analysis on the key targets using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The renoprotective effect was evaluated using a mouse model of diabetic nephropathy (db/db mice) that occurred spontaneously. Validation of the associated targets and pathways was performed using Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemical methods (IHC).Results: The network analysis showed that the TSF pathway network targeted 24 important targets and 149 significant pathways. TSF might have an impact by focusing on essential objectives such as TP53, PTEN, AKT1, BCL2, BCL2L1, PINK-1, PARKIN, LC3B, and NFE2L2, along with various growth-inducing routes. Our findings demonstrated that TSF effectively repaired the structure of mitochondria in db/db mice. TSF greatly enhanced the mRNA levels of PINK-1. WB and IHC findings indicated that TSF had a notable impact on activating the PINK-1/PARKIN signaling pathway in db/db mice, significantly increasing LC3 and NRF2 expression.Conclusion: Our results indicate that TSF effectively addresses DN by activating the PINK-1/PARKIN signaling pathway and enhancing Mitochondrion structure in experimental diabetic nephropathy.Keywords: tangshen formula, diabetes nephropathy, network pharmacology, mitophagy, PINK1/Parkin pathway

Yiming Chen,1,2 Jian Liu,1,2 Chengzhi Cong,1 Yang Li,1 Yuedi Hu1 1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230038, People’s Republic of China; 2Anhui Key Laboratory of Application and Development of Internal medicine of Modern Chinese Medicine, Hefei, Anhui, 230038, People’s Republic of ChinaCorrespondence: Jian Liu, Email liujianahzy@126.comObjective: This study aimed to evaluate the effect of traditional Chinese medicine (TCM) on endpoint events in patients with gouty arthritis (GA).Methods and Materials: A total of 2091 hospitalized GA patients were followed up by telephone, and propensity score matching (PSM) was used to reduce potential bias in the study design. Cox proportional risk model and Kaplan-Meier survival curve were utilized to analyze the impact and time effect of factors on the readmission of GA patients. The differences of laboratory indexes before and after treatment between the low and high exposure groups were compared, and the types and frequencies of medicines in all patients were counted. Association rule analysis was performed to investigate the association between TCM and test indexes or endpoint events.Results: After 1:1 PSM, 187 patients were enrolled in the TCM group and 187 patients in the non-TCM group. The incidence of readmission, new tophus, and all-cause death was lower in the TCM group than that in the non-TCM group (P < 0.05). Cox proportional risk regression analysis showed that TCM, NSAIDs and uric acid lowering drug were independent protective factors for GA readmission. The protective effect was enhanced by the prolongation of TCM treatment and the drug combinations. Kaplan-Meier survival curves indicated a significantly lower readmission rate in the high exposure group than in the low exposure group (P < 0.01). Compared with before treatment, NLR, hs-CRP, UA, TC and other laboratory indexes of the low and high exposure groups were improved after treatment (P < 0.01); The improvement of TG and TC in the high exposure group was more significant than the low exposure group (P < 0.01). The analysis of medicines used by all patients identified the top 20 Chinese herbal medicines and the top 2 Chinese patent medicines. The core drugs identified through association rule analysis that can improve test index and reduce the incidence of endpoint events include Yiyiren, Danshen, and HQC, among others. The network diagram of association rule analysis intuitively shows the relationship between core drugs and “improvement of indicators” and “the absence of endpoint events”.Conclusion: TCM is associated with a reduced incidence of endpoint events in patients with GA.Keywords: gouty arthritis, cohort study, traditional Chinese medicine, Chinese patent medicine, neutrophil to lymphocyte ratio

Chenqi Chang,1 Heng Liu,2 Xiaotong Li,2 Dandan Song,1 Yue Liu,1 Chang Lu,1 Yu Zhen,1 Ying Chen,1 Jinguo Xu,1 Weidong Li,1 Xiaobin Jia,3 Zhipeng Chen,1 Rui Chen1 1School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, 671003, People’s Republic of China; 3School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of ChinaCorrespondence: Rui Chen; Zhipeng Chen, Email chenrui@njucm.edu.cn; czpcpu2000@hotmail.comIntroduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties.Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo.Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage.Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option. Keywords: berberine, polydopamine, ROS-responsive, adhesion retention, ulcerative colitis

Yu Chen,1 Ru Gao,1 Honghui Liu,1 Maoyu Ye,1 Ling Chu,2 Tiansheng Wang1 1Department of Otolaryngology-Head and Neck Surgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Pathology, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Tiansheng Wang, Department of Otolaryngology-Head and Neck Surgery, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha, People’s Republic of China, Email 600923@csu.edu.cnBackground: Individuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology.Methods: We recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated.Results: We identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P< 0.05), and serum MRC1 (AUC=0.742, P< 0.001) and MMP2 (AUC=0.766, P< 0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P< 0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P< 0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils.Conclusion: Circulating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.Keywords: chronic rhinosinusitis with nasal polyps, endotype, eosinophilic, proteomics

Yeping Chen,1,&ast; Daofu Zeng,1,&ast; Guizheng Wei,1,&ast; Zhidong Liao,1,2 Rongyuan Liang,1 Xiajie Huang,1,2 William W Lu,3 Yan Chen1,2 1Department of Bone and Joint Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Orthopedics and Traumatology, the University of Hong Kong, Hong Kong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen, Department of Bone and Joint Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Tel +86-18077790338, Email cy003@connect.hku.hkAbstract: Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. Its global impact is noteworthy, causing significant economic losses and property damage. Despite extensive research, the underlying pathogenesis of OA remain an area of ongoing investigation. It has recently been discovered that the OA progression is significantly influenced by pyroptosis. Pyroptosis is a complex process that involves three pathways culminating in the assembly of Gasdermin-D (GSDMD)-N-terminal (GSDMD-NT) into pores through aggregation on the plasma membrane. The aggregation of GSDMD-NT proteins stimulates the release of inflammatory mediators, such as Interleukin-1β (IL-1β), Interleukin-18 (IL-18), and Matrix Metallopeptidase 13 (MMP13), ultimately leading to cellular lysis. The pyroptosis process in specific cells, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributs factor to the development of OA. Currently, the specific cells that undergo pyroptosis first are not yet fully understood, and it remains unknown whether pyroptosis in one cell can trigger the same process in other cells. Therefore, targeting pyroptosis could potentially offer a novel treatment approach for OA patients. We present a comprehensive analysis of the molecular mechanisms and key features of pyroptosis. We also outline the current research progress on various aspects, including synovial tissue, articular cartilage, extracellular matrix (ECM), and subchondral bone, with a focus on pyroptosis. The aim is to provide theoretical references for the effective management of OA.Keywords: pyroptosis, osteoarthritis, caspases-1/4/5/11, GSDMD, synovium, chondrocytes

Yanbei Duo,1 Shuoning Song,1 Xiaolin Qiao,2 Yuemei Zhang,3 Jiyu Xu,4 Jing Zhang,5 Zhenyao Peng,6 Yan Chen,2 Xiaorui Nie,2 Qiujin Sun,7 Xianchun Yang,7 Ailing Wang,8 Wei Sun,4 Yong Fu,1 Yingyue Dong,1 Zechun Lu,8 Tao Yuan,1,&ast; Weigang Zhao1,&ast; 1Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 3Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 6Department of Dean’s Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 7Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 8National Center for Women and Children’s Health, China CDC, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Yuan; Weigang Zhao, Email t75y@sina.com; xiehezhaoweigang@163.comObjective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6– 12 weeks of gestation) to the second trimester (24– 28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM.Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM.Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy.Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.Keywords: hematological parameters, gestational diabetes mellitus, inflammation, insulin resistance, prospective study

Chengying Hong,1 Yihan Xiong,2 Jinquan Xia,3 Wei Huang,4 Andi Xia,1 Shunyao Xu,1 Yuting Chen,1 Zhikun Xu,1 Huaisheng Chen,1 Zhongwei Zhang5 1Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Neurology Department, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 3Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 4Department of Clinical Microbiology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Huaisheng Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China, Email sunshinic@hotmail.com Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email 716461751@qq.comObjective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality.Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model.Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort.Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.Keywords: sepsis, mortality, LASSO regression, predictive model, ICU

Yang Chen, Xiaoen Bian, Junnan Wang, Fang Yan, Jing Gao, Tao Sun Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Tao Sun, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Email suntaosdph@163.comPurpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data.Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks.Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%.Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.Keywords: loxoprofen sodium hydrogel patch, real-world study, chronic inflammatory pain, non-steroidal anti-inflammatory drugs

Qiang Fu,1 Na Han,1 Na Li,2 Ling Gui,3 Chen Shi,4 Peipei Rong,5 Fan Zeng,1 He Rao,6 Yuan Chen1 On behalf of Cancer Rehabilitation and Palliative Treatment Professional Committee of Hubei Anti Cancer Association1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 3Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 4Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 6Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaCorrespondence: Qiang Fu; Yuan Chen, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei, 430030, People’s Republic of China, Email fqiang2016@163.com; chenyuan008@163.comAbstract: Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the “Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch” (from now on referred to as the “Guidelines”) in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the “Guide”. Finally, all experts of the preparation team certify and finalize the draft. This “Guide” prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.Keywords: fentanyl transdermal patch, reasonable application, medication guidelines

Fangju Lin,1 Weihua Jia,1 Xuemei Li,2 Ying Chen,1 Min Wan1 1Department of Neurology, Beijing Shijingshan Hospital, Shijingshan Teaching Hospital of Capital Medical University, Beijing, 100043, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031, People’s Republic of ChinaCorrespondence: Weihua Jia; Xuemei Li, Email jiawh_sjsh@163.com; lixuemei8806@163.comPurpose: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. This study aims to explore the cognitive profiles stratified by education using MoCA in PD patients with FOG.Patients and Methods: PD patients with FOG (FOG+, n = 52) and without FOG (FOG-, n = 71) were included in our study. MoCA items were categorized into five subsections (attention/working memory, executive function, episodic memory, language, and visuospatial function) referring to previously published criteria. Cognitive assessments were compared based on five subsections between groups stratified by three education levels (0– 6 years, 7– 12 years, and > 12 years). The association of cognitive measurements with FOG were analyzed using binary logistic regression models with adjustment for variables.Results: The total scores and subscores of each subsection of MoCA were similar between two groups of each education level. Further detailed analysis showed that a composite measure labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition), were lower significantly in FOG+ group compared with FOG- group in patients with education year ≤ 6 years. The significant association of Attention-C with FOG held true when controlling for disease duration, but not for H-Y stage, MDS-UPDRS III, HAMA, and HAMD.Conclusion: Overall, our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which will need to be validated in future studies.Plain Language Summary: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. To the best of our knowledge, our study is the first to investigate the cognitive profiles using MoCA stratified by education in Chinese PD patients with FOG. We proposed a novel composite measure derived from MoCA labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition). We found a significant association of Attention-C with FOG existed in PD patients with education year ≤ 6 years when controlling for disease duration, but disappeared for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. It may be attributed to a large extent to the relatively small size of our study population. Our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which need to be further explored and validated in expanded studies with different international populations. Thus, the present study could provide critical implications for ordinary clinical practice where comprehensive neuropsychological batteries are not easily accessible to clinicians.Keywords: Parkinson’s disease, freezing of gait, Montreal Cognitive Assessment, attention, working memory, executive function

Yongjun Huang,1,&ast; Yong Chen,2,&ast; Guoyun Cheng,1,&ast; Wenqiang Li,3 Hongan Zhang,1,4 Chaoqun Yu,1 Jia Fang,1 Jieyi Zuo,1 Ying Li,1 Lei Xu,1 Dawei Sun1 1Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 2Department of Orthopedics, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, People’s Hospital, Qingyuan, 511518, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 4The Second Clinical School of Medicine, Southern Medical University, Guangzhou, 510260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xu; Dawei Sun, Department of Orthopedics, Guangdong Second Provincial General Hospital, 11th Floor, Building 3, No. 466, Xingang Middle Road, Guangzhou, Guangdong Province, 510317, People’s Republic of China, Email orthoxl@163.com; sundw@gd2h.org.cnBackground: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public.Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings.Results: The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days).Conclusion: Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair. Keywords: TA/Cu2+ nanoparticles, carboxymethyl chitosan, wound dressing, antioxidant activity

Tao Huang,1,&ast; Yongling Lv,2,&ast; Wei Wang,1 Yunyao Chen,1 Lixin Fan,1 Zhaowei Teng,3 Xianfeng Zhou,2,4 Hexiao Shen,2 Guang Fu1 1Gastrointestinal Surgery, Wuhan Puren Hospital, Wuhan, People’s Republic of China; 2Maintainbiotech. Ltd. (Wuhan), Wuhan, People’s Republic of China; 3Central Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4School of Life Sciences and Health Engineering, Hubei University of Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hexiao Shen; Guang Fu, Email shenhxmyt@163.com; fuguang71@163.comAbstract: Adverse skin reactions caused by the COVID-19 vaccine have attracted considerable attention. As we all know, the development mechanism of some skin diseases is related to the gut and skin microbiome. A 78-year-old male patient who received the COVID-19 vaccine developed generalized eczema with multiple dense black patches over the body, a widespread rash, erosion, and scabs on his limbs, as well as facial edema. The patient experienced recurrent flare-ups after conventional treatment, but then recovered well without recurrence after undergoing three fecal microbial transplantation (FMT) treatments. This rare case is reported for the first time in this study. This report demonstrates the possible potential of FMT in targeting refractory skin diseases, such as eczema, as well as diseases associated with gut microbiota disturbance after vaccination.Keywords: FMT, eczema, COVID-19 vaccine

Yunhao Yang,1,2 Fang Pang,1– 3 Min Zhou,1,2 Xiao Guo,1,2 Yan Yang,1,2 Wei Qiu,1,2 Cai Liao,1,2 Yang Chen,1,2 Chenglin Tang1,2 1College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3Institute of Sports Biology, Shaanxi Normal University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Chenglin Tang, Email tangchenglin@cqmu.edu.cnBackground: Electroacupuncture (EA) is used to treat inflammatory bowel disease (IBD). Nevertheless, the precise mechanisms by which this approach safeguards against obesity-induced intestinal barrier damage has not been fully understood.Objective: This study aimed to assess whether EA could ameliorate intestinal barrier damage that had been reversed in a mouse model of obesity induced by a high-fat diet (HFD) and whether this repair is correlated with ferroptosis and gut microbiota enhancement.Methods: To assess the potential of EA to prevent obesity and restore the intestinal barrier, we divided in C57BL/6J mice into two groups; one was fed with HFD and another one with a normal diet. Samples of stool, blood, fat, and intestinal epithelium were then evaluated, along with body weight.Results: Following EA, we observed a significant reduction in body weight, fat accumulation, and serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels; an increase was seen in high-density lipoprotein cholesterol (HDL-C) levels. EA also activated the Nrf2 signaling pathway; upregulated the expression of GPX4, FTH1, and SLC7A11; and downregulated the expression of TFR1. In addition, the administration of EA resulted in a notable modification of the gut microbiota composition, characterized by a decrease in the Firmicutes to Bacteroidetes ratio.Conclusion: EA had beneficial effects on weight loss and showed potential ability to repair the intestinal barrier by activating the Nrf2 signaling pathway, inhibiting intestinal inflammation and ferroptosis, and regulating the intestinal microbiota to treat IBD caused by HFD-induced obesity. Keywords: ferroptosis, electrostimulation, acupuncture, Chinese medicine, obesity, intestinal epithelium

Yongjian Chen,1 Jingyun Li,2 Zhixing Zhu,3 Guorong Lyu1,2 1Department of Ultrasound, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Quanzhou Medical College, Quanzhou, Fujian, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of ChinaCorrespondence: Guorong Lyu, Department of Ultrasound, the Second Affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Licheng District, Quanzhou, Fujian, 362000, People’s Republic of China, Tel +86-595-22525702, Email lgr_feus@sina.comPurpose: To evaluate the degree of lung hyperinflation (LH) in patients with stable chronic obstructive pulmonary disease (COPD) by lung ultrasound score (LUS) and assess its value.Patients and Methods: We conducted a study of 149 patients with stable COPD and 100 healthy controls recruited by the Second Affiliated Hospital of Fujian Medical University. The pleural sliding displacement (PSD) was measured, the sliding of the pleura in different areas was observed, and LUS was calculated from both of them. The diaphragm excursion (DE), residual capacity (RV), total lung capacity (TLC), inspiratory capacity (IC) and functional residual capacity (FRC) were measured. We described the correlation between ultrasound indicators and pulmonary function indicators reflecting LH. Multiple linear regression analysis was used. The ROC curves of LUS and DE were drawn to evaluate their diagnostic efficacy, and De Long method was used for comparison.Results: (1) The LUS of patients with stable COPD were positively correlated with RV, TLC, RV/TLC and FRC and negatively correlated with IC and IC/TLC (r1=0.72, r2=0.41, r3=0.72, r4=0.70, r5=− 0.56, r6=− 0.65, P < 0.001). The correlation was stronger than that between DE at maximal deep inspiration and the corresponding pulmonary function indices (r1=− 0.41, r2=− 0.26, r3=− 0.40, r4=− 0.43, r5=0.30, r6=0.37, P < 0.001). (2) Multiple linear regression analysis showed that LUS were significantly correlated with IC/TLC and RV/TLC. (3) With IC/TLC< 25% and RV/TLC> 60% as the diagnostic criterion of severe LH, the areas under the ROC curves of LUS and DE at maximal deep inspiration for diagnosing severe LH were 0.914 and 0.385, 0.845 and 0.543, respectively (P < 0.001).Conclusion: The lung ultrasound score is an important parameter for evaluating LH. LUS is better than DE at maximal deep inspiration for diagnosing severe LH and is expected to become an effective auxiliary tool for evaluating LH.Keywords: chronic obstructive pulmonary disease, lung hyperinflation, ultrasound, pleural sliding displacement, pulmonary function

Yi Yao,1,&ast; Juan Li,2,&ast; Wenwu Sun,1,&ast; Chaoping Ma,2,&ast; Ning Ning,1 Jiaoyan Li,1 Tongtian Ni,1 Menglu Gui,1 Ying Chen,1 Bing Zhao,1 Jiyuan Zhang,2 Jiyue Zhu,3 Chengjin Gao,2 Huiqiu Sheng,1 Enqiang Mao1 1Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiu Sheng, Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China, Tel +86-15801971839, Email shenghq803@163.com Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +86-18221088783, Email gaochengjin@xinhuamed.com.cnPurpose: Both nonthyroidal illness syndrome (NTIS) and disseminated intravascular coagulation (DIC) are commonly occurred in sepsis. The objective of this study is to evaluate the association between NTIS and DIC, as well as their impacts on the mortality in adults with sepsis.Patients and methods: A total of 1219 septic patients in two Chinese academic centers from October 2012 and October 2022 were enrolled in analysis. We conduct logistic regression models to analyze the independent risk factors for DIC. Modified Poisson regression models are used to estimate the relative risk (RR) of NTIS on the 28 days mortality in septic patients with DIC. Correlation analysis between thyroid function parameters and coagulation parameters is performed with Pearson coefficient be reported.Results: DIC is diagnosed on 388 (31.8%) of all the 1219 enrolled septic patients within 72 hours after admission. In multivariate logistic regression models, NTIS (OR 3.19; CI 2.31– 4.46; p< 0.001) is a statistically significant independent risk factor for DIC after adjustment for potential confounders. Twenty-eight days mortality is significantly higher in DIC patients complicated with NTIS compared with the other DIC patients (23.2% vs 14.0%, p=0.024). This result is also robust in different modified Poisson regression models (Model 1: RR 1.46; CI 1.25– 1.70; p< 0.001; Model 2: RR 1.35; CI 1.14– 1.60; p< 0.001; Model 3: RR 1.18; CI 1.02– 1.37; p=0.026). Correlation analysis reveals that the thyroid function parameters of FT3, FT4 and TSH only have weak correlations with coagulation parameters of platelet count, fibrinogen, FDP, D-dimers, PT, APTT and INR in sepsis.Conclusion: NTIS is an independent risk factor for DIC in adults with sepsis. DIC patients complicated with NTIS have significantly higher severity and higher rate of mortality.Keywords: sepsis, low T3 syndrome, nonthyroidal illness syndrome, thyroid function, disseminated intravascular coagulation

Rehua Wang,1,2,&ast; Yongjun Lin,3,&ast; Mao Chen,4 Wei Wang,5 Yongli Chen,6 Xiaoxia Qiu,7 Xing Miao1,2 1Department of Cardiology, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 2Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3Department of General Medicine, the First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 4Department of Scientific Research, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 5Department of Psychiatry, Fuzhou Neuro-Psychiatric Hospital Affiliated to Fujian Medical University, Fuzhou, 350008, People’s Republic of China; 6Department of Cardiology, Fujian Provincial Hospital South Branch, Fuzhou, 350028, People’s Republic of China; 7Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Miao, Department of Cardiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, No. 134 East Street, Gulou District, Fuzhou, 350001, People’s Republic of China, Tel +86 13763810443, Email miaoxingph@outlook.comPurpose: Temperature changes unfavorably impact on cardiovascular disease. However, the association between temperature changes and coronary artery disease (CAD) is not well documented. This study aimed to explore the association between daily mean temperature and daily CAD hospital admissions on the southeast coast of China (Fuzhou City).Methods: A total of 1883 CAD patients who underwent percutaneous coronary intervention between 2017 and 2019 were obtained. The severity of CAD was evaluated by the Gensini score. Distributed lag non-linear model (DLNM) combined with a quasi-Poisson regression model was used to examine the delayed effect between daily mean temperature and daily CAD hospital admissions. Stratified analyses were performed by Gensini score and severity of lesions. The relative risk (RR) with a 95% confidence interval (CI) was used to assess the relationship.Results: Extreme cold (8°C) (RR=0.49, 95% CI: 0.25– 0.99) and moderate cold (10°C) (RR=0.56, 95% CI: 0.31– 0.99) daily mean temperature with a lag of 0– 20 days were correlated with lower risk of daily CAD hospital admissions. Moderate heat (30°C) (RR=1.80, 95% CI: 1.01– 3.20) and extreme heat (32°C) (RR=2.02, 95% CI: 1.01– 4.04) daily mean temperature with a lag of 0– 20 days related to a higher risk of daily CAD hospital admissions. Similar results were observed for daily mean temperature with a lag of 0– 25 days. Stratified analysis showed the lagged effect of daily mean temperature (lag 0, 0– 5, 0– 15, 0– 20, and 0– 25 days) on the daily CAD hospital admissions was observed only in patients with a Gensini score ≤ 39 (tertile 1).Conclusion: Cold temperatures may have a protective effect on daily CAD hospital admissions in the Fuzhou area, whereas hot temperatures can have an adverse effect.Keywords: temperature, coronary artery disease, gensini score, daily admissions, lag effect