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Shuanggang Chen,1,2,&ast; Han Qi,1,2,&ast; Hongtong Tan,1,2,&ast; Fei Cao,1,2 Lin Xie,1,2 Tao Huang,1,2 Ying Wu,3 Chunyong Wen,1,2 Yujia Wang,1,2 Lujun Shen,1,2 Weijun Fan1,2 1Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Interventional Therapy, Shenzhen second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weijun Fan, Email fanwj@sysucc.org.cn; Lujun Shen, Email shenlj@sysucc.org.cnBackground: Salvage liver transplantation is promising for hepatocellular carcinoma(HCC) recurrence post-ablation but is significantly affected by recurrence beyond Milan Criteria (RBM).Materials and Methods: A retrospective cohort study of potentially transplantable HCC patients undergoing ablation between 2007 and 2017 assessed median time to recurrence beyond Milan Criteria(TRBM) via Kaplan-Meier curves and predictive capacity of recurrence and RBM for overall survival(OS) via Receiver Operating Characteristic Curves, and identified independent risk factors for TRBM and RBM via Cox and binary logistic regression models.Results: We enrolled 191 potentially transplantable patients with early-stage HBV-related HCC ≤ 3 cm who underwent ablation. During a median follow-up of 7.64 years, HCC recurrence occurred in 126 patients(65.9%), with RBM 86 patients(45.0%). The median TRBM was 10.54 years. Cumulative survival rates without RBM at 3, 5, 8, 10, and 13 years were 77.3%, 65.9%, 56.5%, 51.0%, and 37.6%, respectively. Multivariable analysis identified older age, C-reactive protein(CRP)≥ 1.81 mg/L, and platelet(PLT)≤ 80× 109/L as independent risk factors for TRBM. Also, cirrhosis, CRP≥ 1.81 mg/L and PLT≤ 80× 109/L were identified as independent risk factors of the occurrence of RBM. Elevated Platelet-CRP Score(PCS), integrating CRP and PLT, correlated significantly with an increased incidence of RBM and a more aggressive phenotype, characterized by vascular invasion or metastatic dissemination (P< 0.05). Notably, RBM was a superior predictive indicator for OS compared to recurrence (P< 0.05).Conclusion: When using ablation as a bridge to liver transplantation for solitary HBV-related early HCC (≤ 3 cm), it is crucial first to identify key preoperative features, including high CRP, low PLT, cirrhosis, and older age. Keywords: hepatocellular carcinoma, hepatitis B virus, ablation techniques, transplantable liver transplantation, recurrence beyond the Milan criteria

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

Yunfeng Wu,1 Yuxi Liu,2 Han Wu,1 Mengying Tong,1 Linyao Du,1 Shuangsong Ren,1 Ying Che1 1Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Liaoning, Dalian, People’s Republic of China; 2Department of Ultrasound, Shandong Second Medical University Affiliated Hospital, Shan Dong, Weifang, People’s Republic of ChinaCorrespondence: Ying Che, Email yche1964@163.comAbstract: Breast cancer is one of the most common types of cancer in women worldwide and is a leading cause of cancer deaths among women. As a result, various treatments have been developed to combat this disease. Breast cancer treatment varies based on its stage and type of pathology. Among the therapeutic options, ultrasound has been employed to assist in the treatment of breast cancer, including radiation therapy, chemotherapy, targeted immunotherapy, hormonal therapy, and, more recently, radiofrequency ablation for early-stage and inoperable patients. One notable advancement is ultrasound-targeted microbubble destruction (UTMD), which is gradually becoming a highly effective and non-invasive anti-tumor modality. This technique can enhance chemical, genetic, immune, and anti-vascular therapies through its physical and biological effects. Specifically, UTMD improves drug transfer efficiency and destroys tumor neovascularization while reducing toxic side effects on the body during tumor treatment. Given these developments, the application of ultrasound-assisted therapy to breast cancer has gained significant attention from research scholars. In this review, we will discuss the development of various therapeutic modalities for breast cancer and, importantly, highlight the application of ultrasound microbubble-targeted disruption techniques in breast cancer treatment.Keywords: ultrasound-targeted microbubble destruction, breast cancer, microbubble, chemotherapy, TME, radiofrequency ablation

Liting Zhong,1,2,&ast; Weiwei Peng,1,2,&ast; Jingyuan Sun,3 Yongyi Luo,3 Hailong Sheng,4 Yi Wu,5 Tonggang Zhou,5 Chaoming Zhou,1,2 Chuanhui Cao1,3 1Department of Oncology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, People’s Republic of China; 2Department of Oncology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 3Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Interventional Radiology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanhui Cao, Department of Oncology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, No. 16 Meiguan Avenue, Ganzhou, Jiangxi, People’s Republic of China, Email huichuancao@163.comPurpose: The optimal timing for combining radiotherapy with immunotherapy in patients with hepatocellular carcinoma (HCC) remains uncertain and affects treatment efficacy and patient outcomes. This study aimed to evaluate and compare the efficacy and treatment-related adverse events (TRAEs) of synchronously administered radiotherapy and programmed cell death protein (PD)-1 inhibitors and sequential administration in patients with HCC.Patients and Methods: We retrospectively enrolled 67 patients with HCC who were undergoing liver radiotherapy and PD-1 inhibitor therapy at two medical centers between July 2017 and April 2023. Additionally, we created an experimental tumor model using 6-week-old female mice to validate our findings.Results: In the concurrent group, the median overall survival was indefinite; however, it was 13 months in the sequential group (95% confidence interval [CI] 6.7– 19.3 months, P=0.010). The median progression-free survival was significantly longer in the concurrent group (12 months, 95% CI 9.5– 14.5 months) than in the sequential group (7 months, 95% CI 1.3– 12.7 months; P=0.043). Grade 3/4 TRAEs occurred in 30.4% (concurrent) and 28.6% (sequential) of patients without any treatment-related deaths. In the mouse model, synchronous treatment significantly inhibited tumor growth compared to sequential treatment (293.4± 45.18 mm3 versus 602.7± 41.68 mm3; P=0.001). Flow cytometry revealed an increased Tregs/CD3+ T cell ratio and a decreased CD8+/Treg cell ratio post-radiotherapy, suggesting an immunosuppressive tumor microenvironment.Conclusion: Synchronous treatment demonstrated superior efficacy in treating HCC compared to sequential treatment, with manageable adverse events. The rapid increase in Tregs after radiotherapy may contribute to the reduced efficacy of sequential radiotherapy plus PD-1 inhibitors.Keywords: immunotherapy, treatment efficacy, adverse events, tumor microenvironment

Leran Wang,1 Lei Liu,2 Huilan Luo,3– 5 Yiling Wu,3– 5 Lingyan Zhu3– 5 1Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang City, People’s Republic of China; 2Department of Endocrinology, Lu’an Hospital of Anhui Medical University, Lu’an City, Anhui Province, People’s Republic of China; 3Department of Endocrinology and Metabolism, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, People’s Republic of China; 4Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, the First Affiliated Hospital of Nanchang University, Nanchang City, People’s Republic of China; 5Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang City, People’s Republic of ChinaCorrespondence: Lingyan Zhu, Jiangxi Branch of National Clinical Research Center for Metabolic Disease, No. 17, Yongwaizheng Street, Nanchang City, Jiangxi Province, People’s Republic of China, Tel +86-13870690788, Email zly982387@126.comBackground/Objective: Considering the uncertain relationship between high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) with diabetic retinopathy (DR),this study investigates the link between Uric Acid to High-Density Lipoprotein Cholesterol (UHR) and DR in T2DM patients, evaluating its potential for DR diagnosis and early prediction.Study Design and Data Collection: This retrospective study analyzed 1450 type 2 diabetes patients, divided into NDR and DR groups by retinal exams. We gathered demographic and clinical data, calculated UHR, and explored its correlation with DR development.Outcomes: Individuals diagnosed with diabetic retinopathy (DR) exhibited a markedly elevated uric acid to high-density lipoprotein cholesterol (UHR) ratio when contrasted with those without DR (NDR), achieving statistical significance with a P-value below 0.001. The Mantel-Haenszel chi-square test for linear association validated a pronounced positive correlation between the UHR ratio and the incidence of DR (P< 0.001). Binary logistic regression analysis revealed that age, glycated hemoglobin (HbA1c), uric acid (UA), high-density lipoprotein cholesterol (HDL-C), and the UHR ratio were all independent risk factors for the development of DR in patients with type 2 diabetes. Furthermore, the receiver operating characteristic (ROC) curve analysis indicated that the UHR ratio was the most precise predictor for diagnosing DR, with an area under the ROC curve (AUC) of 78.4%, a sensitivity of 87%, and a specificity of 60.6%.Conclusion: Our research has found that the UHR ratio is an independent risk factor for diabetic retinopathy (DR) in patients with type 2 diabetes and can serve as a readily available indicator that takes into account both metabolic status and inflammatory status for the early detection of DR.Keywords: uric acid to high-density lipoprotein cholesterol ratio, UHR, Type 2 diabetes mellitus, diabetic retinopathy

Junxing Pan,1 Junqiao Guo,2 Yangjie Wu,3 Xiaoyun Zhao4 1Department of Students’ Affair, Huaibei Normal University, Huaibei, People’s Republic of China; 2School of Educational Science, Anhui Normal University, Wuhu, People’s Republic of China; 3Department of Education, Bozhou University, Bozhou, People’s Republic of China; 4School of Education, Huaibei Normal University, Huaibei, People’s Republic of ChinaCorrespondence: Xiaoyun Zhao, Email zhaoxiaoyun1980@163.comBackground: Negative emotions (depression and anxiety) are highly correlated with mobile phone addiction among college students, but the underlying mechanisms between variables need further exploration. The aim of this study is to further elucidate the relationship between negative emotions and mobile phone addiction among college students, with negative coping styles as the mediating variable and gender as the moderating variable.Methods: A survey was conducted on 509 college students from two universities in Anhui Province, China, covering topics such as mobile phone addiction, depression, anxiety, and negative coping styles. SPSS software was used to analyze the relationship between variables.Results: Depression, anxiety, negative coping styles, and mobile phone addiction are all significantly positively correlated. Negative coping styles mediate the relationship between depression, anxiety, and mobile phone addiction among college students. Gender regulates the relationship between depression/anxiety and mobile phone addiction. Specifically, the impact of negative emotions (depression and anxiety) on mobile phone addiction is greater in the male group than in the female group.Conclusion: This study further reveals the psychological mechanisms behind the relationship between negative emotions (depression and anxiety) and mobile phone addiction. Negative coping styles are the mediating factor in this relationship, while gender is the moderating factor in this relationship.Keywords: mobile phone addiction, depression, anxiety, negative coping styles, college students, gender

Siman Li,1 Binding Wang,1 Jiayao Deng,2 Haiyan Li,2 Yong Wu,3 Yu Fang,2 Bohua Yan,2 Yu Chen2 1School of Clinical Medicine, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China; 2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Chengdu Zhongxiang Pharmaceutical Technology Co., Ltd., Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Bohua Yan; Yu Chen, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email yanbohuagcp@163.com; 735405661@qq.comObjective: Chronic pain strongly affects the quality of life of patients with liver cancer pain. Safe and effective management of cancer-related pain is a worldwide challenge. Traditional Chinese medicine (TCM) has rich clinical experience in the treatment of cancer pain. The Fuzhengxiaoliu patch (FZXLP) is a compound TCM with the effects of detoxification and pain relief and has shown great efficacy in the treatment of patients with liver cancer, but high-quality clinical research that provides research-based evidence is lacking. We designed a randomized, double-blind, placebo-controlled trial to explore and evaluate the efficacy of FZXLP for the treatment of liver cancer pain.Methods: This is a prospective, randomized, double-blind, placebo-controlled trial. The trial will enrol 72 participants with primary liver cancer with cancer pain (damp-heat stagnation and toxin and blood stasis syndrome). The primary objective is to measure the reduction in pain using FZXLP in combination with tegafur, gimeracil and oteracil potassium capsule (S-1) compared to the placebo group with S-1. Pain will be measured by the number of opioids used, Chinese versions of the numerical rating scale (NRS), pain relief rate and number of breakthrough cases of cancer pain (BTcP). The secondary objectives include response evaluation criteria in solid tumors (RECIST), tumor markers, TCM syndrome scores, weight, functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire scores, and self-rating anxiety scale scores. Adverse events (AEs) will be recorded throughout the study.Discussion: This study integrated TCM with clinical research to assess the efficacy and safety of the addition of FZXLP in the treatment of primary liver cancer pain.Trial registration: Chinese clinical trial registry, ChiCTR2300076951, Registered on October 25, 2023. https://www.chictr.org.cn/showproj.html?proj=209608.Keywords: primary liver cancer, traditional Chinese medicine, Chinese herb, cancer pain management, randomized controlled trial

Dong Zhang,1,2 Zeming Zhu,3 Zhangyou He,4 Siwei Duan,3 Qincheng Yi,4 Min Qiu,3 Xingzhen Dai,3 Guang Su,4 Kexin Li,1,2 Lin Xu,1,2 Donghou Liu,1,2 Yabin Wu,1,2 Yong Gao,3 Ruliu Li,3 Shaoju Guo1,2 1Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 2Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China; 4Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of ChinaCorrespondence: Ruliu Li, Science and Technology Innovation Center,Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Baiyun District, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Tel +86-020-39357088, Email lrl@gzucm.edu.cn Shaoju Guo, Gastroenterology Department, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Shenzhen City, Guangdong Province, 518000, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.Methods: A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg− 1) and high-dose (10 g·kg− 1), and mesalazine (50 mg·kg− 1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.Results: Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.Conclusion: Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways. Keywords: ulcerative colitis, enema therapy, neutrophil extracellular traps, Chinese medicine, inflammation

Ruo Zhang, Yang Jiao, Yuchao Wu, Lijing Yan, Chunhong Zhang, Jing Xu On behalf of the China National Diabetic Chronic Complications Study GroupDepartment of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Yang Jiao; Jing Xu, Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi Province, 710004, People’s Republic of China, Tel +86 15029930210; +86 18092746638, Fax +862986320305, Email jyjoan@126.com; xujingjdefy85@163.comPurpose: This study aimed to explore the association of globulin and albumin-to-globulin ratio (AGR) with diabetic kidney disease (DKD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods: This study used data from the China National Diabetic Chronic Complications Study in Shaanxi Province. From April to May 2019, T2DM patients at disease surveillance sites in Shaanxi Province were investigated using a stratified multi-stage sampling method. The participants completed questionnaire surveys, anthropometric and blood pressure measurements, laboratory tests, and fundus photograph examinations. Multivariate Logistic regression and restricted cubic spline model were used to analyze the association of globulin and AGR with DKD and DR, and subgroup analysis was performed according to age, sex, and diabetes duration to test the stability of the results.Results: A total of 1494 T2DM patients were enrolled in this study, including 495 patients with DKD (33.1%) and 341 patients with DR (22.8%). After adjusting for all covariates, globulin and AGR were linearly associated with DKD. For every 1g/L increase in globulin level, the risk of DKD increased by 7% (OR=1.07, 95% CI=1.04, 1.10). For every 1 unit increase in AGR, the risk of DKD was reduced by 55% (OR=0.45, 95% CI=0.28, 0.72). Subgroup analysis showed that the association between globulin and DKD was consistent across all subgroups, and the association between AGR and DKD was consistent across subgroups of age and diabetes duration; however, only in males, higher AGR was associated with a reduced risk of DKD. No association was found between globulin and AGR with DR.Conclusion: Globulin is an independent risk factor and AGR is an independent protective factor for DKD. Screening for DKD should be performed in T2DM patients with high globulin and low AGR levels, especially in men.Keywords: globulin, albumin-to-globulin ratio, diabetic kidney disease, diabetic retinopathy

Yuanhong Wu,1 Huijing Xu,2 Yuxin Wang,1 Xiaohui Wang,3 Shanyu Wu1 1College of Nursing, Yanbian University, Yanji, People’s Republic of China; 2College of Nursing, Seoul National University, Seoul, South Korea; 3Department of Nursing, Binzhou People’s Hospital, Binzhou, People’s Republic of ChinaCorrespondence: Shanyu Wu, Email wusy@ybu.edu.cnAim: To investigate the characteristics of psychological insulin resistance and dyadic coping in elderly diabetic patients and their spouses, and their association with insulin medication adherence.Design: Observational, cross-sectional study.Methods: A convenience sampling method selected 300 elderly diabetic patient-spouse pairs from a community. Data were collected using general information questionnaires, the My Views on Insulin questionnaire, Dyadic Coping questionnaire, and ARMS refill and medication adherence questionnaire. Latent Profile Analysis (LPA) was used to categorize the “psychological-coping” patterns of psychological insulin resistance and dyadic coping among these pairs. Multiple linear regression analysis identified factors influencing insulin medication adherence.Results: Four latent classes were identified: patients and spouses with low resistance-high coping (30.3%), patients with low resistance-moderate coping and spouses with high resistance-low coping (16.3%), patients with high resistance-moderate coping and spouses with moderate resistance-high coping (33.7%), patients and spouses with high resistance-low coping (19.7%). Multiple linear regression analysis showed that the number of chronic diseases a patient has, the use of oral hypoglycemic agents, family per capita monthly income, and latent classes of psychological insulin resistance and dyadic coping significantly affected insulin medication adherence (P< 0.05).Conclusion: It is crucial to consider the psychological insulin resistance and dyadic coping of both patients and their spouses, include both in health plans, and develop comprehensive intervention strategies that address the couple as a unit.Implications for the Profession and/or Patient Care: This study informs healthcare professionals by raising awareness of the different “psychological-coping” characteristics between elderly diabetic patients and their spouses, with insulin medication adherence and reducing the likelihood of readmission.Keywords: diabetes, psychological insulin resistance, dyadic coping, medication compliance, latent profile analysis

Shi Yin,1,&ast; Xiyan Zhao,2,&ast; Tian Li,3,&ast; Xingxuan Li,1 Zongjun Xie,1 Hao Tang,1 Yi Wang,1 Zhiwei Jia,1 Tianlin Wen,1 Yaohong Wu4 1Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Outpatient Department of the Ministry of Foreign Affairs, Beijing, People’s Republic of China; 4Department of Spine Surgery, Ganzhou People’s Hospital, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiwei Jia; Yaohong Wu, Email jiazhiweivip@163.com; wuyaohong1986@126.comPurpose: The debate over the effectiveness of platelet-rich plasma (PRP) versus hyaluronic acid (HA) in treating hip osteoarthritis (HOA) continues. This cross-sectional analysis of overlapping systematic reviews aims to evaluate the efficacy of intra-articular PRP compared to HA for HOA treatment. The goal is to guide decision-makers in selecting the most reliable systematic reviews and to provide treatment recommendations based on the best available evidence.Methods: We conducted comprehensive searches of PubMed, EMBASE, and Cochrane Library databases to identify systematic reviews comparing intra-articular PRP and HA for HOA treatment. The methodological quality of these reviews was assessed, and relevant data were extracted. The Jadad algorithm was applied to determine which reviews provided the most robust evidence.Results: Five systematic reviews were included, all categorized as Level-II evidence. The Assessment of Multiple Systematic Reviews scores ranged from 4 to 9, with a median score of 8. A high-quality systematic review was chosen according to the Jadad algorithm. It is suggested that there were no significant differences observed in the improvement of any short-term outcome scores (mean follow-up of 12.2 months for PRP, 11.9 months for HA), including the Western Ontario and McMaster Universities Osteoarthritis Index, the Visual Analog Scale for pain, and the Harris Hip Score, from pre-injection to post-injection between the groups.Conclusion: There is inconsistency among the conclusions of the overlapping systematic reviews comparing intra-articular PRP and HA for HOA treatment. The best evidence indicates that PRP and HA injections yield similar short-term clinical benefits for patients with HOA. Further studies with larger sample sizes and longer follow-up periods are needed to provide more definitive conclusions.Keywords: platelet-rich plasma, hyaluronic acid, Hip osteoarthritis, systematic review

Qiaohui Ying,1,2,* Mingwei Wang,3,* Zichen Zhao,1,2 Yongwei Wu,1,2 Changyun Sun,1,2 Xinyi Huang,1,2 Xin Zhang,1,2 Jie Guo1,2 1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, People’s Republic of China; 3Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Guo, Department of Orthodontics, School and Hospital of Stomatology, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13583104999, Fax +86 53188382923, Email kqgj@sdu.edu.cnPurpose: Sleep apnea (SA), associated with absent neural output, is characterised by recurrent episodes of hypoxemia and repeated arousals during sleep, resulting in decreased sleep quality and various health complications. Mitochondrial DNA copy number (mtDNA-CN), an easily accessible biomarker in blood, reflects mitochondrial function. However, the causal relationship between mtDNA-CN and SA remains unclear. This study aimed to investigate the causality between mtDNA-CN and SA while identifying potential mediating brain imaging phenotypes (BIPs).Methods: Two-sample bidirectional Mendelian randomisation (MR) analysis was performed to estimate the causal relationship between mtDNA-CN and SA, with further validation using Bayesian framework-based MR analysis. A two-step approach was employed to evaluate causal relationships between BIPs, mtDNA-CN and SA, utilising the “product of coefficients” method to assess the mediating effects of BIPs. Multiple testing errors were corrected using the Benjamini–Hochberg method.Results: Genetically predicted mtDNA-CN had a negative causal effect on SA (OR = 0.859, 95% CI = 0.785– 0.939, P = 3.20× 10− 4), whereas SA did not have a causal effect on mtDNA-CN (OR = 1.0056, 95% CI = 0.9954– 1.0159, P = 0.2825). Among 3935 BIPs, two features related to white matter microstructure served as partial mediators: the second eigenvalue from diffusion MRI data analysed by tract-based spatial statistics in the right posterior thalamic radiation, with a mediation proportion of 11.37% (P = 0.0450), and fractional anisotropy in the right sagittal stratum, with a mediation proportion of 12.79% (P = 0.0323).Conclusion: This study demonstrated a causal relationship between mtDNA-CN and SA, with specific brain white matter microstructure phenotypes potentially acting as mediators. These findings highlight the potential of mtDNA-CN as a biomarker for SA and underscore its relevance in guiding future therapeutic strategies targeting mitochondrial health and brain white matter microstructure.Keywords: mitochondrion, sleep disorder, brain structure, magnetic resonance imaging, causal relationship

Kai Zhang,1 Dandi Ma,1 Yunxiao Wu,2 Zhifei Xu1 1Clinical Department of National Clinical Research Center for Respiratory Diseases, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Zhifei Xu, Clinical Department of National Clinical Research Center for Respiratory Diseases, Beijing Children’s Hospital, Beijing, 100045, People’s Republic of China, Email zhifeixu@aliyun.comPurpose: Chronic intermittent hypoxia (CIH) is considered one of the main pathophysiological mechanisms of obstructive sleep apnea (OSA). CIH can further lead to cognitive dysfunction by inducing processes such as neuroinflammation and oxidative stress. The hippocampus is primarily associated with cognitive functions such as learning and memory. This study aimed to explore the effects of CIH on cognitive function and hippocampal neurons in mice and to reveal its potential molecular mechanisms.Methods: SPF-grade C57BL/6J mice (n=36) were selected as subjects and divided into control, mild CIH, and severe CIH groups (12 mice per group). Cognitive function was assessed using the Morris water maze test, and hippocampal neuron numbers and morphological changes were observed using HE staining and Nissl staining. Additionally, differential genes and pathways were revealed through RNA sequencing (RNA-seq) and bioinformatics analysis. We examined oxidative stress-related biochemical markers in the hippocampal tissue and used Western Blot to verify changes in the expression of potential key genes. Statistical analyses were performed using ANOVA and post hoc tests to ensure robust comparisons between groups.Results: CIH mice exhibited significant cognitive impairment, including decreased learning and memory abilities. The severe CIH group had a longer escape latency compared to the mild CIH group (p < 0.001) and the control group (p < 0.01), while the mild CIH group took longer than the control group (p < 0.01). In the probe test, the severe CIH group showed a significant decrease in platform crossings (p < 0.01) and target quadrant dwell time (p < 0.05), while the mild CIH group exhibited a reduction in target quadrant dwell time (p < 0.05). Abnormal hippocampal neuron morphology was observed, with a significant reduction in hippocampal neurons (p < 0.05). RNA-seq analysis revealed numerous differentially expressed genes, mainly enriched in biological processes such as inflammation and oxidative stress, as well as multiple signaling pathways. Specifically, downregulated LepR, SIRT1, and Nrf2 genes were found to exacerbate oxidative stress and neuroinflammation, impairing neuronal integrity and cognitive function. Further validation showed increased oxidative stress levels in hippocampal tissue and downregulation of key gene expression. Western blot analysis confirmed significantly reduced expression of LepR (p < 0.01), SIRT1 (p < 0.001), and Nrf2 (p < 0.001) in the severe CIH group.Conclusion: While oxidative stress and inflammation are well-established mechanisms in CIH-induced cognitive impairment, our study provides novel insights by identifying the specific roles of LepR, SIRT1, and Nrf2 in this process. The downregulation of these key genes suggests potential new targets for therapeutic intervention. Importantly, the differential expression patterns observed in varying degrees of hypoxia severity highlight the potential for tailored therapeutic strategies that modulate these pathways in response to the intensity of hypoxic exposure. These findings offer unique opportunities for developing targeted therapies aimed at mitigating CIH-related cognitive decline and neural damage. However, a key limitation of this study is the exclusive use of animal models, which may not fully replicate human pathophysiology. Further studies are needed to validate these findings in clinical settings and to explore the regulatory relationships between the key genes involved.Keywords: obstructive sleep apnea, chronic intermittent hypoxia, cognitive impairment, hippocampal neurons, RNA sequencing, oxidative stress, inflammation

Yunxiao Wu,1,2 Changming Wang,3 Yingchao Jiang,4 Ya Zhang,5 Li Zheng,2 Xiao-lin Ning,1,6– 8 Zhifei Xu5 1School of Instrumentation Science and Optoelectronic Engineering, Beihang University, Beijing, 100191, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 3Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4College of Psychology and Mental Health, North China University of Science and Technology, Tangshan, 063210, People’s Republic of China; 5Clinical Department of National Clinical Research Center for Respiratory Diseases, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 6Key Laboratory of Ultra-Weak Magnetic Field Measurement Technology, Ministry of Education, School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, 100191, People’s Republic of China; 7Institute of Large-Scale Scientific Facility and Centre for Zero Magnetic Field Science, Beihang University, Hangzhou, 310051, People’s Republic of China; 8National Institute of Extremely-Weak Magnetic Field Infrastructure, Hangzhou, 3100051, People’s Republic of ChinaCorrespondence: Xiao-lin Ning, Beihang University, 37 Xueyuan Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +8613691352196, Email ningxiaolin@buaa.edu.cn Zhifei Xu, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56 Nanlishi Road, Xicheng, Beijing, 100045, People’s Republic of China, Tel +8613521660077, Email zhifeixu@aliyun.comObjective: To investigate how attention is affected in children with obstructive sleep apnea (OSA) using the attention network test (ANT) combined with event-related potential (ERP) and time-frequency analysis.Methods: Eighty-seven children aged 6– 11 years with symptoms of snoring or mouth breathing during sleep were recruited from the Sleep Center of Beijing Children’s Hospital from May to July, 2023. All participants completed the Mini-mental State Examination and Attention Deficit Hyperactivity Disorder rating scale. We acquired 32-lead electroencephalography (EEG) data while participants performed the ANT, followed by Polysomnography.Results: Of the 87 children, 21 had no OSA, 49 had mild OSA, and 17 had moderate to severe (MS) OSA. Each group had similar questionnaire scores, similar response time and accuracy for the different ANT conditions. There are alterations in the processing of three separate components of the attentional network in children with OSA. The amplitude of the N3 component at the FZ electrode in the MS OSA group was lower than that of the non-OSA and mild OSA groups (all P< 0.05). In the executi control network phase, the energy of alpha band was higher in the MS OSA group than in the mild OSA group (Z=− 2.624, P=0.026). The mean amplitude of the N3 component at the FZ electrode was correlated with the obstructive apnea-hypopnea index (OAHI) (r=0.232, P=0.038).Conclusion: Attention impairment was observed as a reduced N3 in the frontal area in the MS OSA group, which was correlated with the OAHI. However, questionnaire and behavioral performance did not differ significantly between groups. These findings suggest that the N3 amplitude is a sensitive neuroelectrophysiological marker of OSA-related cognitive impairment.Keywords: OSA, child, attention, event-related potential, time-frequency

Yaxin Guo,1,&ast; Jun Liao,1,&ast; Shunian Li,1 Yiyan Shang,2 Yunxia Wang,2 Qingxia Wu,3 Yaping Wu,1 Meiyun Wang,1 Fengshan Yan,1 Hongna Tan1 1Department of Radiology, People’s Hospital of Zhengzhou University & Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Radiology, People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 3Beijing United Imaging Research Institute of Intelligent Imaging & United Imaging Intelligence (Beijing) Co., Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongna Tan; Fengshan Yan, Department of Radiology, People’s Hospital of Zhengzhou University & Henan Provincial People’s Hospital, Weiwu Road, Zhengzhou City, 450003, People’s Republic of China, Tel +86-13526766042 ; +86-18637134815, Email natan2000@126.com; mountyan857@163.comBackground: Histological grade is an acknowledged prognostic factor for breast cancer, essential for determining clinical treatment strategies and prognosis assessment. Our study aims to establish intra- and peritumoral radiomics models using T2WI and DWI MR sequences for predicting the histological grade of breast cancer.Methods: 700 breast cancer cases who had MRI scans before surgery were included. The intratumoral region (ITR) of interest was manually delineated, while the peritumoral region (PTR-3 mm) was automatically obtained by expanding the ITR by 3 mm. Radiomics features were extracted using the intra- and peritumoral images from T2WI and DWI sequences on breast MRI. Then, the key features with the strongest predictivity of histological grade were selected. Finally, 9 predictive radiomics models were established based on T2WI-ITR, T2WI-3mmPTR, DWI-ITR, DWI-3mmPTR, T2WI-ITR + 3mmPTR, DWI-ITR + 3mmPTR, (T2WI + DWI)-ITR, (T2WI + DWI)-3mmPTR and (T2WI + DWI)-ITR + 3mmPTR.Results: The (T2WI + DWI)-ITR + 3mmPTR contained 13 DWI features which included a shape feature, a texture feature, and 11 filtered features, as well as 10 T2WI features, all of which were filtered features. Among the 9 models, the combined models showed better performance than the single models in both the training and test sets, especially for the (T2WI + DWI)-ITR + 3mmPTR radiomics model. The (T2WI + DWI)-ITR + 3mmPTR radiomics model achieved a sensitivity, specificity, accuracy, and AUC of 80.4%, 72.4%, 75.0%, and 0.860 in the training set, and 68.9%, 70.5%, 70.0%, and 0.781 in the test set. Decision curve analysis (DCA) showed that the (T2WI + DWI)-ITR + 3mmPTR model had the greatest net clinical benefit compared to the other models.Conclusion: The intra- and peritumoral radiomics methodologies using T2WI and DWI MR sequences could be utilized to assess histological grade for breast cancer, particularly with the (T2WI + DWI)-ITR + 3mmPTR radiomics model demonstrating significant potential for clinical application.Keywords: breast cancer, histological grade, MRI, T2WI, DWI, radiomics

Yun Wu,1 Huixin Shi,1 Wei Li,1 Yijun An,1 Yuhan Shao,1 Xia Rao,1 Nicholas R Waterfield,2 Wei Wang,3 Guowei Yang1 1Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Warwick Medical School, Warwick University, Coventry, UK; 3Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yun Wu; Guowei Yang, Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10-63139853 ; +86-10-63139130, Email wuyun@ccmu.edu.com; yangguowei@hotmail.comPurpose: Pneumocystis jirovecii pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on P. jirovecii drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of P. jirovecii in non-HIV patients in China, providing a reference for drug usage.Methods: We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including P. jirovecii infection (n = 14) and P. jirovecii colonization (n = 31). This analysis also considered clinical characteristics, P. jirovecii burden, treatment response, and prognosis.Results: Compared to the P. jirovecii colonization, P. jirovecii infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, P< 0.05) with higher P. jirovecii burden (P< 0.05) and worse prognosis (P< 0.05). Additionally, patients with P. jirovecii infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.Conclusion: Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.Keywords: Pneumocystis jirovecii pneumonia, mutation, drug resistance, prognosis, non-HIV

Xiangyong Li,1 Zeyang Zhou,1 Chenxi Zhou,1 Mengya Xiong,2 Chungen Xing,1 Yong Wu1 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People’s Republic of China; 2Operating Room, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yong Wu; Chungen Xing, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People’s Republic of China, Email wuyong6302@163.com; xingcg@suda.edu.cnPurpose: Preoperative albumin to alkaline phosphatase ratio (AAPR) and inflammatory burden index (IBI) are prognostic indicators for a multitude of cancers, and our study focuses on evaluating the prognostic significance of the AAPR and the IBI on rectal cancer (RC) patients to provide a more accurate guideline for patient prognosis.Patients and Methods: This study enrolled patients who underwent laparoscopic rectal cancer surgery from January 2016 to January 2021. We utilized three machine learning approaches to select variables most relevant to prognosis in the training cohort. Finally, based on the screened variables, a nomogram was established to predict RC patients’ overall survival (OS). The improvement in predictive ability and clinical benefit was assessed through the concordance index (C-index), receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA).Results: A total of 356 patients were enrolled and they were randomly divided into a training cohort (60%, n=214) and a validation cohort (40%, n=143). Overall survival (OS) was worse for patients in either the low AAPR or the high AAPR group, whereas patients in the low AAPR with both high IBI group had the lowest OS (P< 0.001). Finally, five variables were obtained after screening the best variables by three machine learning, and the nomogram was constructed. In both the development and validation cohorts, the C-index values exceeded 0.85, indicating that the predictive model has a strong predictive performance in terms of overall survival. The calibration curves and the decision curve analysis (DCA) showed that the nomogram demonstrated a superior benefit.Conclusion: Preoperative AAPR and IBI can serve as effective indicators for predicting the OS of RC patients. We have developed a nomogram for predicting the OS of patients who underwent laparoscopic rectal cancer surgery.Keywords: albumin to alkaline phosphatase ratio, inflammatory burden index, rectal cancer, overall survival, prediction nomogram

Qiuping Ye, Yang Hu, Qijing Xing, Yun Wu, Ye Zhang Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Ye Zhang, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, People’s Republic of China, Tel +86-551-63869485, Email zhangye_hassan@sina.comPurpose: The routine perioperative use of opioids has recently been questioned due to opioid-related side effects, which can be potentially harmful in geriatric patients. This study aimed to evaluate the effects of opioid-free anesthesia in geriatric patients undergoing hip surgery.Patients and Methods: A total of 121 patients, aged 60 years or older, undergoing elective hip surgery were randomized to receive either opioid-free anesthesia with dexmedetomidine and esketamine (OFA group) or balanced anesthesia with opioids (CON group). All patients received a preoperative fascia iliaca block and postoperative patient-controlled analgesia using tramadol. The primary outcome was the incidence of a composite of anesthetic-related complications (nausea and vomiting, hypoxemia, ileus, urinary retention and delirium) within 48 hours postoperatively. The hemodynamics, postoperative pain and quality of life were also assessed.Results: The incidence of composite adverse events was significantly reduced in the OFA group compared with the CON group (35.0% vs 62.3%, estimated difference: 27.3%, 95% confidence interval: 10.2%– 44.4%, P = 0.003). Notably, patients in the OFA group experienced less postoperative nausea and vomiting (P = 0.040), and hypoxemia (P = 0.025) compared with those in the CON group. However, the incidences of postoperative ileus, urinary retention and delirium were comparable between the two groups. Also, patients in the OFA group had less pain in motion at 24 h postoperatively, as well as less risks of intraoperative hypotension and bradycardia (P < 0.05). No significant differences in the postoperative quality of life were observed between the two groups.Conclusion: Opioid-free anesthesia with dexmedetomidine and esketamine reduced postoperative anesthetic-related complications and provided improved hemodynamic stability in geriatric patients undergoing hip surgery.Keywords: nonopioid, dexmedetomidine, esketamine, geriatric, hip injuries

Jianhua Wu,1,2 Yisha Wu,1 Peng Jin,3 Xiaoxue Zi,3 Yuzhu Wan,1 Kaiyue Sun,1,4 Li Shi,1,3 Deyun Wang5 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Binzhou People’s Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Li Shi, Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 0531 83086278, Fax +86 0531 83086279, Email shili126@sina.com Kaiyue Sun, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250022, People’s Republic of China, Tel +86 0531 83086277, Fax +86 0531 83086279, Email 18354159626@163.comBackground: Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules in eukaryotes, involved in many essential biological processes. However, their role in allergic rhinitis (AR) has not been extensively studied.Methods: The expression levels of hsa_circRNA_100791 were measured using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from AR patients. The biological function of hsa_circRNA_100791 in AR was investigated through RNA-seq and a series of in vitro experiments. Western blotting, luciferase reporter assays, and rescue experiments were conducted to elucidate the molecular mechanisms underlying hsa_circRNA_100791. Additionally, a mouse model was used to assess the functional role of hsa_circRNA_100791 in vivo.Results: Upregulation of hsa_circRNA_100791 was observed in both PBMCs and nasal mucosa of AR patients. In vitro, increased expression of hsa_circRNA_100791 promoted the production of pro-inflammatory mediators (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-18, IL-33, TNF-α, and NF-κB) and inhibited IL-2 and IFN-γ. Conversely, knockdown of hsa_circRNA_100791 both in vitro and in vivo alleviated AR symptoms, reduced pro-inflammatory mediators, and enhanced IL-2 and IFN-γ levels. Mechanistically, we found hsa_circRNA_100791 contributing to the pathological processes of AR, which upregulate TRIM13 via sponging miR-487b-5p.Conclusion: Our study demonstrated that hsa_circRNA_100791 mitigates the inhibitory effect of miR-487b-5p on Trim13 by directly binding to miR-487b-5p. This interaction regulates the expression of inflammatory factors and facilitates AR. Thus, hsa_circRNA_100791 could be a promising new therapeutic target for AR.Keywords: allergic rhinitis, hsa_circ_100791, miR-487b-5p, Trim13, diagnosis, inflammation, NF-κB

Shiyu Li, Yang Zhou, Yini Wen, Yali Wu, Fan Liu, Yan Ding Department of Pediatric Immunology, Wuhan Children’s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, People’s Republic of ChinaCorrespondence: Yan Ding; Fan Liu, Department of Pediatric Immunology, Wuhan Children’s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, People’s Republic of China, Email dingyanmx@163.com; 2548948461@qq.comBackground: Intravenous immunoglobulin (IVIG) resistance may be an increased risk of coronary artery lesions which is the serious complication of Kawasaki disease (KD). Early and accurate identification of IVIG-resistant patients has an important clinical value.Objective: To establish a new predicting model by detecting the pyroptosis markers with other clinical indicators.Methods: A total of 144 children with KD who were hospitalized in Wuhan Children’s Hospital from January 2022 to December 2022 were enrolled in this prospective study, among whom 120 had IVIG-sensitive KD and 24 had IVIG-resistant KD. NLRP3, ASC, CASP1, and GSDMD were quantified in peripheral blood cells of all children by using Real-time Quantitative Polymerase Chain Reaction (QRT-PCR) assay. The enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of cytokines like IL-1β and IL-18. Logistic regression analysis was performed to identify independent risk factors for resistance to IVIG in children with KD. These meaningful variables were assigned values based on odds ratios and became components of the new risk assessment model. The prediction efficiency of this model was tested and evaluated based on the receiver operating characteristic (ROC) curves.Results: 1. IVIG-resistant KD group had significantly lower mRNA expression of CASP1 than IVIG-sensitive KD group (P< 0.05). 2. IVIG-resistant KD group had significantly higher level of serum procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) and lower level of serum natrium (Na) than the IVIG-sensitive KD group (P< 0.05). 3. The assessment model had a sensitivity of 91.7% and a specificity of 69.2% in the prediction of IVIG-resistant KD (P< 0.001).Conclusion: Combined examination by CASP1 and above laboratory indexes has clinical practical value for the diagnosis of IVIG-resistant KD.Keywords: Kawasaki disease, resistance to intravenous immunoglobulin, CASP1, child

Duo Zhang,1,&ast; Yuan You,2,&ast; Lin Cai,3,4 Wenjing Zhang,5 Kai Zhang,6– 8 Yibo Wu9 1College of Media and International Culture, Zhejiang University, Hangzhou, 310000, People’s Republic of China; 2Social Genetic and Developmental Psychiatry Centre, King’s College London, London, SE5 8AF, UK; 3School of Chinese National Community, Southwest Minzu University, Chengdu, 610041, People’s Republic of China; 4School of Marxism, Sichuan Institute of Industrial Technology, Deyang, 618500, People’s Republic of China; 5Shandong Provincial Health Promotion and Education Center (Shandong Traditional Chinese Medicine Promotion and Communication Center), Jinan City, Shandong Province, 250002, People’s Republic of China; 6Department of Geriatric Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 7Department of Gastroenterology, Dongying People’s Hospital, Dongying, Shandong, 257091, People’s Republic of China; 8Ruiyang Pharmaceutical Company Limited Postdoctoral Research Workstation, Zibo, Shandong, 256100, People’s Republic of China; 9School of Public Health, Peking University, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibo Wu, School of Public Health, Peking University, Beijing, 100191, People’s Republic of China, Email bjmuwuyibo@outlook.com Kai Zhang, Department of Geriatric Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China, Email zhangkaizhijia1987@163.comIntroduction: Problematic internet use (PIU) is a significant issue during adolescence. It is recognized as a condition for further study in the DSM-5 and may also be a consequence of underlying psychopathologies, as suggested by previous studies. Poor family communication is an important predictor of adolescent PIU. However, it remains unclear how family communication impacts adolescent PIU from the perspective of underlying psychopathologies. This study tested the chain mediating effect of loneliness and depression as well as the moderating effect of developmental stage in this chain mediation model to uncover the mechanisms underlying this association.Methods: This cross-sectional study recruited a total of 1,377 participants (53% male) from 23 provinces across China, all aged 12 to 17. Family communication was assessed using the FCS-10, which measures aspects such as openness, emotional expression, and problem-solving abilities within family interactions. PIU was assessed using the PIUQ-SF-6, loneliness was measured by the T-ILS, and depression was assessed using the PHQ-9. The chain mediating effects were tested using bias-corrected percentile bootstrap (sample = 5000).Results: The results indicated that (a) poor family communication was positively associated with adolescent PIU; (b) loneliness and depression mediated the link between family communication and adolescent PIU; (c) loneliness and depression sequentially mediated the link between family communication and adolescent PIU; (d) the developmental stage of adolescence (early vs late) moderated the relationship between depression and PIU in the chain mediation model.Conclusion: This study reveals that depression, as a potential underlying psychopathology, may precede PIU. It also establishes a link between family communication and PIU, showing that loneliness resulting from poor family communication contributes to the development of depression in adolescents. The connection between depression and PIU is particularly pronounced in late adolescence. These findings highlight the importance of addressing underlying psychopathologies when screening and treating adolescent PIU.Keywords: adolescent, family communication, problematic internet use, loneliness, depression

Yaping Shen,1,2,&ast; Yijiu Wu,3,&ast; Hai Zhuang,4 Zhumei Chen,5 Qiong Zhang,5 Peixin Li,5 Jing Wang,3 Zhi Huang,1 Qingfan Zeng3,5 1Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 2Department of Interventional Radiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 3College of Anesthesiology, Guizhou Medical University, Guiyang, 550002, People’s Republic of China; 4Department of Infectious, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 5Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi Huang, Department of interventional radiology, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550002, People’s Republic of China, Email huangzhi@gmc.edu.cn Qingfan Zeng, Department of Anesthesiology, The Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China, Email 445483296@qq.comBackground: Isoflurane, as an anesthetic drug, has a neurotoxic effect on the developing brain tissue. Compound 21 (C21) has been reported to be neuroprotective and ameliorate stroke effects. However, the mechanism by which C21 protects against nerve damage remains unclear.Methods: Animal and cellular models of brain injury were constructed using isoflurane (ISO) in neonatal SD rats and primary rat neuronal cells (PRNCs). After treatment with C21, the ultrastructure and morphology of the hippocampus in the model rats were assessed using the transmission electron microscope and H&E staining. Methylation or apoptosis-related genes or proteins were examined using immunohistochemistry, RT-qPCR, and Western blot. The levels of inflammatory factors were monitored using the ELISA kits. m6A modification was analyzed by Dot blot and MeRIP-qPCR. Cell proliferation and apoptosis were also tested using Edu and TUNEL staining.Results: C21 suppresses apoptosis and inflammation and improves hippocampal morphology in ISO-induced neonatal rats. Mechanistically, C21 upregulates m6A modification, PPAR-a, BCL-2, and METTL3 in ISO-induced neonatal rats and ISO-treated PRNCs. C21 promotes cell proliferation, enhances BCL-2 m6A modification, and reduces inflammation by upregulating METTL3 by upregulating METTL3 in ISO-treated PRNCs.Conclusion: These findings suggest that C21 enhances neuronal cell survival and morphology and up-regulates methylation and Bc1-2 levels, potentially offering a therapeutic strategy for neuroprotection in clinical settings, particularly in cases of neurotoxic exposure. The mechanism may be related to the upregulation of METTL3. Keywords: compound 21, isoflurane, METTL3, anesthesia, neuron

Jingkai Di,1,2,&ast; Liying Song,2,3,&ast; Yaru Liu,2,4,&ast; Zhibo Zhang,1,2 Yawen Wu,2 Tingting Chen,2,5 Chuan Xiang1 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Medical University, Taiyuan, People’s Republic of China; 3The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4The Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5The Fifth Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Xiang, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 15903410351, Email chuanxiang@sxmu.edu.cnPurpose: Despite the association between peripheral blood inflammatory biomarkers and a range of inflammatory diseases, the role of these biomarkers in osteoarthritis (OA) progression remains unclear. Additionally, whether alterations in these inflammatory markers impact the prognosis of OA patients remains an understudied area. The aim of our study was to investigate the specific associations between peripheral blood inflammatory markers and OA progression and OA-related mortality.Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 through 2018. The primary outcomes were all-cause mortality, cardiac mortality, and renal disease mortality, with information on the corresponding mortality rates for each participant obtained through association with the National Death Index (NDI). Multivariate logistic regression models were used to examine the relationship between peripheral blood lymphocyte counts and OA, and restricted cubic spline (RCS) analysis was utilized to assess whether there was a nonlinear relationship with OA and mortality of OA patients. Interaction and stratified analyses were employed to explore the association between peripheral blood leukocyte counts and OA.Results: This study included 1077 OA patients and 21,612 non-OA participants. In model 3 fully adjusted for covariates, eosinophil-to-lymphocyte ratio (ELR) and eosinophil (EOS) were positive risk factors promoting the development of OA (OR = 3.26, 95% CI: 1.49– 7.14; OR = 1.79, 95% CI: 1.12– 2.88). In stratified models for age, sex, BMI, smoking status, and alcohol consumption, the associations of ELR and EOS with OA were significantly different. RCS curves showed a J-shaped relationship between ELR and EOS and all-cause mortality in patients with OA. ELR was also found to significantly up-regulate cardiac mortality and renal mortality in patients with OA (OR = 3.92, 95% CI: 1.68– 9.14; OR = 22.55, 95% CI: 6.55– 77.70), while EOS was only significantly positively correlation (OR = 3.68, 95% CI: 1.94– 7.01).Conclusion: A significant relationship was found between ELR, EOS and OA. In addition, ELR and EOS were identified as potential predictors of mortality from different causes in patients with OA.Keywords: eosinophil to lymphocyte ratio, osteoarthritis, eosinophil, all-cause mortality

Cui Xie,1 Yang Xiang,1 You Wu,1 Youen Zhang1,2 1Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Arteriosclerosis Cardiovascular Disease Clinical Medical Research Center of Hubei Province, Shiyan, Hubei, 442000, People’s Republic of ChinaCorrespondence: Youen Zhang, Email zye112@hotmail.comAbstract: We present a patient of a 46-year-old female patient was admitted to our hospital due to chest tightness and shortness of breath that lasted for over a month. Echocardiography revealed left-ventricle diameter (anteroposterior) of 54 mm, electrocardiogram showed sinus bradycardia, and QRS duration of 90 ms. The patient experienced no chest tightness or shortness of breath, and there was a marked improvement in exercise tolerance and quality of life after cardiac contractility modulation implantation.Keywords: heart failure, cardiac contractility modulation, dilated cardiomyopathy, ventricular remodeling

Qingqing Zhang,1,2,&ast; Jing Zheng,1,&ast; Guoyu Wang,1,3 Suyun Jiang,1 Peng Gao,1 Si Sun,1 Xiangwei Ding,3 Yucheng Wu3 1Department of Pan-Vascular Management Center, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucheng Wu; Xiangwei Ding, Email 2567181759@qq.com; dingxw1208@126.comObjective: To determine the prevalence of Cardiovascular-Kidney-Metabolic (CKM) Syndrome and identify risk factors, including occupational factors, lifestyle factors and clinical measurements, and female-specific risk enhancers among healthcare workers in China.Methods: A cross-sectional study was conducted among healthcare workers at Taizhou People’s Hospital between April and May 2024. We collected data through surveys and laboratory results. Univariate and multivariate logistic regression analyses were performed to identify predictors of CKM syndrome and female-specific risk enhancers.Results: A total of 1110 participants were recruited (197 male; 913 female; mean age 34.8± 7.9). Almost 90% of male healthcare workers and 60% of female healthcare workers met the criteria for CKM syndrome (stage 1 or higher). Additionally, most male CKM syndrome patients were in stages 2– 3 (53.81%), while most female CKM syndrome patients were in stage 1 (35.82%). Multivariate logistic regression analysis revealed that, compared to those with over 20 years of work duration, a work duration of less than 10 years was a protective factor for CKM Syndrome. Additionally, more than 8 hours of sedentary time was identified as a risk factor compared to less than 2 hours (OR = 1.376, 95% CI 1.027– 1.844, P < 0.05). Receiver operating characteristic analysis showed that body mass index (BMI) was superior to fasting plasma glucose, glycated hemoglobin, triglycerides, and the triglyceride glucose product index in predicting CKM Syndrome, with area under the curve values of 0.884 vs 0.638, 0.708, 0.745, and 0.761, respectively (P < 0.05 for all). BMI was identified as an independent risk factor for female-specific risk enhancers.Conclusion: CKM syndrome is prevalent among healthcare workers in Chinese tertiary hospitals, with males generally presenting at more advanced stages than females. BMI is a key predictor of CKM syndrome and female-specific risk enhancers.Keywords: cardiovascular-kidney-metabolic syndrome, BMI, healthcare workers, triglyceride glucose product index

Nan Lin,1,&ast; Dang Li,1,2,&ast; Si Lin,1 Yilang Ke,1 Jianping Lu,3 Yinrong Wu,1 Tianwen Huang,1,3 Huashan Hong1 1Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Clinical Research Center for Senile Vascular Aging and Brain Aging, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Nursing Department, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huashan Hong, Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Clinical Research Center for Senile Vascular Aging and Brain Aging, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86 591 8621 8525, Fax +86 591 8621 8545, Email 15959159898@163.comPurpose: The prevalence of osteoporosis in elderly individuals is high, and osteoporosis is strongly associated with chronic inflammation. The monocyte-to-high-density lipoprotein ratio (MHR) is acknowledged as a marker for assessing systemic inflammation and oxidative stress, and changes in the MHR are associated with many chronic disease prevalent among the elderly population. This study investigated the relationships between the MHR and the incidence of osteoporosis in older adults, along with its predictive value.Patients and Methods: Data from 563 participants aged ≥ 70 years were retrospectively analysed. The haematological parameters were evaluated via established methodologies, utilizing fasting blood samples collected from the participants. The absolute monocyte count was used to calculate the MHR (MHR=monocyte/HDL-C). BMD was measured by dual-energy X-ray absorptiometry. The results were evaluated via comparative statistical analyses, Spearman correlation, logistic regression analyses, and receiver operating characteristic (ROC) curve analysis.Results: The differences in the MHR were statistically significant among the osteoporosis groups (p < 0.001). Spearman correlation analysis revealed a positive correlation between the MHR and BMD. Furthermore, stratifying the sample into four groups on the basis of quartiles of MHR (M1, M2, M3, and M4) revealed a decreased risk of osteoporosis in the highest quartile compared with the lowest quartile (p < 0.001). Multiple logistic regression analysis revealed that BMI and the MHR were independent risk factors for osteoporosis. The area under the ROC curve and the cut-off value of the MHR were 0.710 and 0.308(109/mmol), with specificity and sensitivity of 0.599 and 0.735, respectively (95% CI: 0.668~0.752, p < 0.0001).Conclusion: A low MHR was associated with a greater risk of senile osteoporosis. In clinical practice, the MHR has shown predictive value for senile osteoporosis, contributing to early intervention and treatment of this disease.Keywords: senile osteoporosis, monocyte-to-high-density lipoprotein ratio, bone mineral density, inflammation, senescence

Si Wang,1,2,&ast; Lin Zhang,1,2,&ast; Yigao Wu,3 Jun Ma1,2 1Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 2Department of Psychiatry, Wuhan Hospital for Psychotherapy, Wuhan, People’s Republic of China; 3Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ma, Department of Psychiatry, Wuhan Mental Health Center, No.89, Gongnongbing Road, Wuhan, Hubei, People’s Republic of China, Email majun0313@wo.cn Yigao Wu, Department of Medical Psychology, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, People’s Republic of China, Email wuyigao2000@126.com.Background: Major depressive disorder (MDD) and metabolic syndrome (MetS) are both major health threats nowadays, and the relationship between them is complex and close. The purpose of this paper is to compare differences in the prevalence and risk factors of MetS in first hospitalized patients with MDD with and without antidepressant exposure.Methods: A total of 636 first hospitalized MDD patients (study group) with antidepressant exposure and 345 drug-naïve patients (control group) were included in this study. Their socio-demographic data, routine biochemical indices, and psychological symptom assessment were collected.Results: There was no difference in the prevalence of MetS between the study group and the control group (F = 2.49, p = 0.115). Factors affecting MetS and its severity differed between the two groups, in the study group, the identified risk factors for MetS were onset age (B = 0.05, p < 0.001, OR = 1.05, 95% CI = 1.02– 1.08), TSH level (B = 0.42, p < 0.001, OR = 1.53, 95% CI = 1.39– 1.68). Meanwhile, in the control group, the identified risk factors for MetS were more extensive and they were, onset age (B = 0.11, p < 0.001, OR = 1.12, 95% CI = 1.07– 1.16), suicidal behavior (B = 1.54, p = 0.007, OR = 4.65, 95% CI = 1.51– 14.33), HAMD scores (B = 0.23, p = 0.008, OR = 1.26, 95% CI = 1.06– 1.49) and TSH levels (B = 0.33, p < 0.001, OR = 1.39, 95% CI = 1.17– 1.65). The number of risk factors identified was lower in the study group.Conclusion: Antidepressant use was associated with greater MetS severity but did not affect overall prevalence. Antidepressants appear to modify MetS risk factors, highlighting the need to differentiate these effects from those in drug-naïve patients when developing MetS interventions for the MDD population.Keywords: major depressive disorder, metabolic syndrome, antidepressant-exposed, drug-naïve, risk factor

Fangyuan Lai,1,&ast; Xiuqiong Huang,2,&ast; Jiao Peng,3 Nannan He,4 Zhongqiang Cao,1 Yuhui Wu,4 Wei Li,5 Zebin Chen,1 Xuejuan Li1 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pharmacy, The First People’s Hospital of Zhaoqing, Zhaoqing, People’s Republic of China; 3Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 5Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuejuan Li, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China, Email xuejuanli@126.comObjective: The first-line treatment for severe Pneumocystis carinii pneumonia (PCP) is trimethoprim-sulfamethoxazole (TMP/SMZ). Here, we report a case involving 6-month-old child with a PCP infection, highlighting the role of clinical pharmacists in providing individualized pharmaceutical care and guidance through the process of therapeutic drug monitoring (TDM).Methods: The clinical pharmacist monitored the concentration of TMP/SMZ in the serum, urine and sputum of a 6-month-old child with PCP infection. To improve the serum levels of TMP/SMZ, the dose of TMP/SMZ was increased, while infusions of other medications were reduced to decrease the rate of drug excretion. Additionally, the patient received other supportive medications to enhance clinical therapeutic efficacy.Results: Clinical pharmacists observed that, despite administration of a sufficient dose of TMP/SMZ, plasma concentration of TMP/SMZ remained below the therapeutic window, while urine concentrations were extremely high. This phenomenon was attributed to Augmented Renal Clearance (ARC), often seen in critically ill patients and associated with increased renal clearance. Throughout treatment, the concentrations of SMZ remained below the minimum effective concentration, while the concentrations of TMP fell within the effective target range. However, sufficient therapeutic effects were ultimately achieved and observed in the patient, likely due to improved drug distribution in lung tissue (sputum) and the patient’s recovering immune functions. Finally, thanks to individualized pharmaceutical care from clinical pharmacists and the combined efforts of clinicians, the patient was discharged after 58 days of hospitalization.Conclusion: Throughout treatment, the clinical pharmacist played a vital role in optimizing the treatment plan based on the serum, urine and sputum concentrations of TMP/SMZ and providing pharmaceutical care to ensure a safe, rational and effective medications in children. Individualized dose adjustments, particularly high-dose TMP/SMZ guided by TDM, can significantly enhance the management of PCP in pediatric patients and support clinical pharmacists in delivering individualized pharmaceutical care.Keywords: Pneumocystis carinii pneumonia, trimethoprim/sulfamethoxazole, therapeutic drug monitoring, plasma drug concentration

Jie Wang,1 Yuanbo Wu,2 Meng Mao,3 Hailong Bing,1 Liwei Sun,1 Wei Xu,1 Wangli Tian,1 Zhengyuan Xia,4,5 Xiaogao Jin,1,6 Qinjun Chu1 1Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Anesthesiology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 3Center for Advanced Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 5Department of Anesthesiology, The University of Hong Kong, Hong Kong; 6Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of ChinaCorrespondence: Xiaogao Jin; Qinjun Chu, Email jinxiaoagao@zzu.edu.cn; jimmynetchu@163.comPurpose: We aim to detect the effects of sivelestat on renal ischemia-reperfusion associated with AKI and also explore the underlying mechanism.Materials and Methods: Mice, aged between 8 and 12 weeks, were randomly allocated among four distinct groups, respectively normal saline sham group(C), normal saline surgery group(I), sivelestat (50 mg/kg) sham group(S), sivelestat (50 mg/kg) surgery group(SI) (n=6, each group). In the surgical groups, the renal pedicles of mice were clamped with non-traumatic micro-aneurysm clamps, resulting in ischemia of the kidneys for 45 minutes. This was followed by a period of reperfusion lasting 24 hours. Sham group mice underwent the identical surgery produced without clamping renal pedicles. Mice blood was obtained from eyeballs, and Serum creatinine and blood urea nitrogen levels were measured. After a 24-hour period of reperfusion, the mice were euthanized, and their kidneys were gathered for various analyses, including Western Blot (WB) analysis, RT-PCR, immunofluorescence (IF), hematoxylin and eosin (H&E) staining, and Tunel assay.Results: Pretreatments with sivelestat decreased renal Neutrophil elastase (NE), serum creatinine, and blood urea nitrogen levels after renal ischemia-reperfusion. Sivelestat also reduced histological damage and cell apoptosis in kidneys following ischemia-reperfusion injury (IRI). In addition, the sivelestat administration diminished the levels of mRNA expression of interleukin 6 (IL-6), Macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α in the kidneys during IRI. The kidney tissues of the SI group had significantly mitigated TLR4, Myd88, and NF-κB p-p65 protein expression levels compared to the I group (all P< 0.05).Conclusion: We demonstrated a previously unidentified mechanism that sivelestat effectively attenuates AKI-induced renal dysfunction, possibly through suppressing the TLR4/Myd88/ NF-κB pathway.Keywords: neutrophil elastase, ischemia reperfusion injury, renal dysfunction, inflammation

Shuping Song,1,&ast; Jieqiong Liu,2,3,&ast; Wei Su,1 Haitao Yu,4 Binbin Feng,1 Yinshan Wu,1 Feng Guo,1 Zhenwei Yu2 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 4Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 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.cnBackground: Tigecycline is considered one of the last resorts for treating infections caused by multidrug-resistant bacteria. Continuous renal replacement therapy (CRRT) is widely used in critically ill patients, especially those with acute kidney injury or severe infections. However, pharmacokinetic data for tigecycline in patients receiving CRRT are limited.Methods: This was a single-center prospective clinical study with intensive sampling that included critically ill patients who received tigecycline and CRRT. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis, visual predictive checks, and numerical predictive checks. Pharmacokinetic/pharmacodynamic target attainment and cumulative fraction of response analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT.Results: In total, 21 patients with 167 concentrations were included. A two-compartment model adequately described the tigecycline concentration–time points, but no covariates were found to adequately explain the viability in the pharmacokinetic parameters of tigecycline. The typical values of CL, Q, V1 and V2 were 4.42 L/h, 34.8 L/h, 30.9 L and 98.7 L, respectively. For most infections, the standard regimen of 50 mg/12 h was deemed appropriate, expect for skin and soft skin tissue infections and community-acquired pneumonia caused by Acinetobacter baumannii and Klebsiella pneumoniae, which required a dosage regimen of 100 mg/12 h or higher.Conclusion: A tigecycline PPK model describing critically ill patients undergoing CRRT was successfully developed. The optimized dosage regimens for various infections are recommended.Keywords: tigecycline, population pharmacokinetics, critically ill, continuous renal replacement therapy

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

Mingmin Guo,1,2 Yi Wu,2,3 Maijiao Peng,1,2 Nenqun Xiao,1,2 Zhijun Lei,1,2 Zhoujin Tan2,3 1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha, People’s Republic of China; 3School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Zhijun Lei, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email lzj-707@163.com Zhoujin Tan, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email tanzhjin@sohu.comBackground: Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP’s therapeutic effects, providing experimental evidence for its mechanism of action.Methods: A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with Folium sennae. After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured.Results: SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.05), and a significant negative correlation with Prevotellaceae UCG− 001, Rikenella (p< 0.05), Acinetobacter (p< 0.05), Parasutterella (p< 0.05), and Lacticaseibacillus (p< 0.05). TNF-α levels showed a significant negative correlation with Lacticaseibacillus (p< 0.05), Prevotellaceae UCG− 001 (p< 0.01), Parasutterella (p< 0.05), and Candidatus Saccharimonas (p< 0.05). IL-6 levels exhibited a significant negative correlation with Rikenella (p< 0.05), Acinetobacter (p< 0.05), Prevotellaceae UCG− 001 (p< 0.05), Lacticaseibacillus (p< 0.01), and Parasutterella (p< 0.05), and a significant positive correlation with Faecalibaculum (p< 0.05), Chryseobacterium (p< 0.01), and A2. Serum TMAO levels showed a significant positive correlation with Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.01), and hepatic TMAO levels exhibited a significant positive correlation with Chryseobacterium (p< 0.05).Conclusion: SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.Keywords: Diarrhea, Kidney-Yang Deficiency Syndrome, Sishen Pill, CutC, Cecal microbiota, TMAO, Inflammation

Peng Gao,1 Yanshuo Wu,1 Xinhui Wu,1 Jing Bai,2 Kangkang Shen,1 Yanling Yin1 1Department of Critical Care Medicine, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Yanling Yin, Department of Critical Care Medicine,Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang City, Hebei Province, 050000, People’s Republic of China, Tel +86-13833467312, Email 47400548@hebmu.edu.cnObjective: To explore the effect of the Integrated Management Model of Doctor-Nurse-Pharmacist Collaboration on the Safety of Intravenous Therapy in Critically Ill Patients.Methods: 1587 patients who were hospitalized in the Intensive Care Department of the Fourth Hospital of Hebei Medical University in China from January 2021 to December 2022 were selected. 768 patients before the implementation of the integrated medical, nursing, and drug management model were selected as the control group, and 819 patients who implemented the integrated medical, nursing, and drug management model were selected as the observation group.Results: Compared with the control group, the incidence of drug compatibility contraindications in the observation group decreased from 3.5% to 1.5% (χ2=6.957 P=0.008), the central venous catheter (CVC) blockage rate decreased from 2.5% to 1.0% (χ2=5.249 P=0.022), the daily incidence of catheter related bloodstream infections decreased from (1.84 ± 2.17) to (0.91 ± 1.19)(t=6.988 P=0.015), and the incidence of peripheral venous treatment related complications decreased from 10.3% to 2.9% (χ2=16.663 P=0.000). Among them, the incidence of phlebitis decreased from 5% to 1.6% (χ2=4.817 P=0.028). The incidence of drug exudation decreased from 3.4% to 0.8% (χ 2=0.031 P=0.019). The incidence of extravasation has decreased from 2.5% to 0.4% (χ2=0.044 P=0.027). The differences were statistically significant (P< 0.05).Conclusion: The Integrated Management Model of Doctor-Nurse-Pharmacist Collaboration significantly reduced the incidence of catheter-related bloodstream infections (CRBSI), drug incompatibility, and other intravenous therapy-related complications, thereby enhancing the safety of intravenous therapy in critically ill patients.Keywords: severe patients, integration of doctor-nurse-pharmacist, intravenous treatment safety, complication

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

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

Linjun Tang, Yong Xu, Liangwei Wang, Jingjing Pan, Yong Wu Department of Neurosurgery, The Second People’s Hospital of Wuhu, Wuhu, People’s Republic of ChinaCorrespondence: Yong Wu, Department of Neurosurgery, The Second People’s Hospital of Wuhu, 6 Du Chun Road, Wuhu, Anhui, 241000, People’s Republic of China, Tel +86-17775461605, Email wuyong760617@163.comBackground: This study explores risk determinants for participants’ lower extremities deep vein thrombosis (DVT) in the perioperative phase after spontaneous intracerebral hemorrhage (SICH), thereby informing more effective clinical prevention and treatment strategies.Methods: During the period spanning October 2021 to March 2024, clinical data from 96 participants who received surgical treatment for spontaneous cerebral hemorrhage was analyzed in a retrospective study. Participants were classified into DVT and negative-DVT groups within the first week post-surgery. We used univariate logistic regression and multivariate logistic regression analyses to assess the impact of various clinical variables on DVT. A nomogram model was constructed to forecast the occurrence of early DVT following SICH surgery. The model’s performance was assessed and validated using receiver operating characteristic (ROC) curves and bootstrap resampling.Results: Among the 96 participants, 46 developed DVT. Significant differences were noted in age, D-dimer levels, fibrinogen degradation products, Caprini scores, and total surgical bleeding volume between the groups. Multivariate analysis revealed that Caprini score (the values of OR, 95% CI, and P are 1.962, 1.124– 3.424, and 0.018, respectively) and total surgical bleeding volume (the values of OR, 95% CI, and P are 1.010, 1.002– 1.018, and 0.017, respectively) were risk variables contributing to DVT occurrence. The area under the receiver operating characteristic curve was 0.918 (95% CI, 0.821– 0.988). The calibration curve showed good prediction accuracy.Conclusion: The Caprini score and total surgical bleeding volume are meaningful self-reliant risk variables contributing to DVT occurrence in postoperative participants with SICH. We have created a straightforward and efficient model to predict early DVT post-SICH surgery. This model serves as a valuable clinical tool for evaluating individual risk and enhancing decision-making processes.Keywords: spontaneous intracerebral hemorrhage, perioperative postoperative period, lower extremities deep vein thrombosis, caprini score, total surgical bleeding volume

Jinqi Ding,1,&ast; Yue Wu,1,&ast; Hanxiaoran Li,1 Shengsheng Wang,1 Jia Cai,2 Hong Cheng,3 Sugai Liang1 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Hangzhou City University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sugai Liang, Email liangsugai@zju.edu.cnPurpose: Network modeling has been suggested as an effective method to explore intricate relationships among antecedents, mediators, and symptoms. In this study, we aimed to investigate whether the severity of depressive symptoms in college students affects the multivariate relationships among anhedonia, smartphone addiction, and mediating factors.Methods: A survey was conducted among 1347 Chinese college students (587 female) to assess depressive symptoms, anhedonia, addictive behaviors, anxiety, and insomnia. The participants were categorized the non-depressive symptom (NDS) and depressive symptom (DS) groups based on a cut-off score of 5 on the 9-item Patient Health Questionnaire-9. Network analysis was performed to investigate the symptom-to-symptom influences of symptoms in these two groups.Results: The network of the DS group was more densely connected than that of the NDS group. Social anticipatory anhedonia was a central factor for DS, while withdraw/escape (one factor of smartphone addiction) was a central factor for NDS. The DS group exhibited greater strength between the PHQ9 score and social anticipatory anhedonia, as well as between the PHQ9 score and alcohol misuse score, compared to the NDS group. On the other hand, the NDS group had higher strength between anxiety and feeling lost, as well as between anxiety and withdraw/escape, compared to the DS group.Conclusion: The findings suggest that there is a close relationship between social anhedonia, smartphone addiction, and alcohol consumption in the DS group. Addressing on ameliorating social anhedonia and smartphone addiction may be effective in preventing and managing depression in college students.Keywords: depressive symptoms, anhedonia, smartphone addiction, network analysis, college students

Jiayue Zhou,1,2 Yingxiang Wu,1,2 Zhiyan Lu,1,2 Yan Wang1,2 1Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan Province, 671000, People’s Republic of China; 2National-Local Joint Engineering Research Center of Entomoceutics, Dali University, Dali, Yunnan Province, 671000, People’s Republic of ChinaCorrespondence: Yan Wang, Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan Province, 671000, People’s Republic of China, Tel +86 0872-2257401, Email jessica9428@sina.comPurpose: Rodgersia sambucifolia Hemsl (also known as Yantuo) is a traditional Chinese medicine commonly utilized as a medicinal herb with its rhizomes, mainly used to regulate the immune function of the human body. However, relatively few studies have investigated its active components and potential mechanisms of action in vivo.Methods: First, the chemical composition in vitro was identified and analyzed using the UPLC-Q-TOF MS/MS technique. Cyclophosphamide (CTX) was then administered intraperitoneally to rats to establish an immunosuppression model. Physiological and biochemical parameters, organ indices, and histopathological findings were evaluated for efficacy. Subsequently, potential biomarkers in rat serum were identified using multivariate statistical analysis and enriched and topologized using online platforms such as MetaboAnalyst and KEGG to reveal the critical metabolic pathways and their roles in the immunomodulatory network. Finally, the integrated analysis of components in vivo and in vitro, along with metabolic pathways, was performed using network pharmacology and molecular docking technology to elucidate the mechanisms of their roles in organismal immunity.Results: A total of 28 chemical components in vitro were identified, while pharmacodynamic experiments confirmed the immunomodulatory effects of Yantuo, especially in the high-dose administration group. Metabolomics analysis showed that 37 potential immune-related biomarkers were identified in positive and negative ion modes, involving 16 metabolic pathways such as arginine biosynthesis, pyrimidine metabolism, and riboflavin metabolism. The results of network pharmacology and molecular docking indicated that Yantuo may affect 7-O-galloyl-catechin, Cynaroside, Quercetin-7-O-beta-D-glucopyranoside, and 1.6-bis-O-galloyl-beta-D-glucose through interactions with the immune system, with significant pathways of action including galactose metabolism, glycolysis/gluconeogenesis, pyrimidine metabolism, and riboflavin metabolism.Conclusion: In our experiments, we confirmed the organismal modulatory effect of Yantuo on immunocompromised rats, clarified the key components, target proteins, and pathways of its possible action, and provided possibilities for follow-up studies. Keywords: immunosuppression, Yantuo, metabolomics, network pharmacology, molecular docking

Chong Zhang, Jianqing Xu, Ming Wang, Yue He, Yumei Wu Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yumei Wu, Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, 17 Qihelou St, Dongcheng District, Beijing, 100006, People’s Republic of China, Email wym597118@ccmu.edu.cnPurpose: The aim of this study was to explore the immune subtypes of endometrial cancer (EC) and its characteristics by immunogenes from the perspective of multidimensional genomics (multi-omics).Patients and Methods: Immune subtypes were carried out using an unsupervised non-negative matrix factorization clustering (NMF) method and their characteristics were analysed. Key genes were identified using random forest analysis. A predictive model for immune subtypes and their clinical prognosis were constructed. The relationship between immune subtypes and molecular subtypes was investigated.Results: Two immune subtypes C1 and C2 were available. C2 patients were younger, less graded, had significantly higher immune cell infiltration, immune checkpoint expression, tumor neoantigens, tumor mutation load than C1 (P< 005). S100A9, CD3D, CD3E, HLA-DRB1 and IL2RB were the key genes with significant survival outcomes. S100A9 expression was lower in C2 than C1, and IL2RB, HLA-DRB1, CD3E and CD3D expression was higher than C1 (P< 0.05). The predictive accuracy of five key genes for immune subtypes was good, with a Receiver operating characteristic of 0.941. The incidence of TP53abn type in C2 was significantly lower than that of C1, and the incidence of POLE type was significantly higher than that of C1 (P< 0.0001).Conclusion: EC can be divided into two immune subtypes based on immunogenes. Low expression of S100A9 and high expression of IL2RB, HLA-DRB1, CD3E, and CD3D suggest sensitivity to immunotherapy and a good prognosis.Keywords: endometrial cancer, immune subtype, immunotherapy, multidimensional genomic, tumor immune microenvironment

Jinyu Lai,1 Yijun Wu,2 Yong Xiang,1 Yun Wang3 1Department of Pain, Taihe Hospital, Hubei University of Medicine, Hubei, People’s Republic of China; 2Department of Radiology, Taihe Hospital, Hubei University of Medicine, Hubei, People’s Republic of China; 3Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yun Wang, Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Tel +86-10-13521611825, Email wangyun129@ccmu.edu.cn Yong Xiang, Department of Pain,Taihe Hospital, Hubei University of Medicine, Hubei, 442000, People’s Republic of China, Tel +86-719-13972451941, Email 411734468@qq.comPurpose: Currently, minimally invasive intervention surgery for cervical spondylotic radiculopathy mostly involves the use of cervical dorsal root ganglion (DRG) block or radiofrequency modulation therapy. Here, we proposed a novel transverse ultrasound-guided approach for puncturing the cervical dorsal root ganglion at the level of joint column for radiofrequency treatment.Patients and Methods: A retrospective analysis of the clinical data of 30 patients with cervical spondylotic radiculopathy admitted to the Pain Department of Taihe Hospital Affiliated with Hubei Medical University from January 2021 to March 2024 was performed. During surgery, motor electrical stimulation was used to induce movement in the nerve-innervated area, and the relationship between the puncture needle tip and the cervical DRG position was verified using a C-arm X-ray machine. The numerical rating scale (NRS) was used for preoperative and postoperative pain assessment, clinical treatment effectiveness was evaluated, surgical duration and the associated complications were also recorded.Results: Thirty patients exhibited clear cervical DRG images under ultrasound guidance, and the punctures were successful in all patients. Motor electrical stimulation induced movement in the corresponding nerve innervation area in the range of 0.3– 0.8 mv in all patients. No serious complications occurred during the procedure.Conclusion: The transverse ultrasound-guided approach for puncturing the cervical dorsal root ganglion at the level of joint column for radiofrequency treatment is effective, convenient, and safe.Keywords: ultrasound guidance, neck DRG, cervical spondylotic radiculopathy, pulse RF

Huabin Wang,1– 4 Rui Zhang,1,3,4 Jing Xu,1,3,4 Min Zhang,1,3,4 Xueyun Ren,1,3,4 Yuhui Wu5 1Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China; 2Postdoctoral Mobile Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Jining Key Laboratory for Prevention and Treatment of Severe Infection in Children, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 4Shandong Provincial Key Medical and Health Discipline of Pediatric Internal Medicine, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 5Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xueyun Ren; Yuhui Wu, Email renxueyun2006@163.com; wyuhoo@163.comObjective: Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR).Methods: A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated.Results: A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69– 18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy.Conclusion: The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.Keywords: pediatric sepsis, NLPR, prognosis, clinical prediction model

Donglin Jiang,1 Yangxue Wu,1 Ling Liu,1 Yajing Shen,1 Tiandong Li,1 Yin Lu,1 Peng Wang,2 Changqing Sun,2 Kaijuan Wang,2 Keyan Wang,3 Hua Ye1 1College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Hua Ye, College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86 186-3853-6001, Fax +86 371-67781018, Email yehua@zzu.edu.cnBackground: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021).Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI).Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors.Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.Keywords: Asia, gastrointestinal tumors, burden, trends

Shutong Ren,1,&ast; Siyu Chen,2,&ast; Jingru Huang,3 Rong Yu,1 Yunli Wu,4 Xian-E Peng1,4 1Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen, 361104, People’s Republic of China; 3Department of Clinical Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 4Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-E Peng; Yunli Wu, Email fmuxe@163.com; wuyunli422@163.comObjective: This study aimed to explore the association between serum uric acid (sUA) levels and metabolic-associated fatty liver disease (MAFLD) in Southeast China.Methods: We performed a cross-sectional study of 2605 subjects who underwent physical examination between 2015 and 2017 in Southeast China. To explore the association between sUA levels and the risk of MAFLD, we employed logistic regression, restricted cubic spline (RCS), subgroups and multiplicative interaction analysis.Results: Logistic regression analysis showed a positive association between sUA and MAFLD [aOR total population (95% CI)= 1.90 (1.49 ~ 2.42)], [aOR male (95% CI)= 2.01 (1.54 ~ 2.62)], [aOR female (95% CI)= 1.15 (0.62 ~ 2.11)], respectively. The RCS plot presented a significant nonlinear dose–response relationship between sUA levels and MAFLD risk, and the risk of MAFLD increased significantly when sUA> 5.56 mg/dL (Pnonlinear< 0.001). Subgroups analysis revealed that the positive association between sUA and MAFLD was consistent across strata of gender, age, BMI, drinking status, smoking status and tea drinking status. Significant associations between sUA and MAFLD were not only found in males but also existed in subjects whose age ≤ 60, BMI ≥ 24 kg/m2, drinkers, smokers and tea-drinkers. Adjusted ORs were estimated to be 2.01, 1.95, 2.11, 2.29, 2.64 and 2.20, respectively. Multiplicative interactions were not observed between gender, age, drinking status, smoking status, tea drinking status and sUA (all P interaction> 0.05).Conclusion: According to our study, sUA was positively associated with the risk of MAFLD. Additionally, the risk of MAFLD increased significantly when sUA levels exceeded 5.56 mg/dL. Our study may help clarify whether sUA plays a diagnostic role in MAFLD.Keywords: metabolic-associated fatty liver disease, serum uric acid, risk, cross-sectional study

You Jiang,1,2 Wenbo Li,1,2 Jun Zhang,1 Kun Liu,1 Yuee Wu,3 Zhengguang Wang1 1Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of General Surgery, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Electrocardiogram Diagnosis, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230060, People’s Republic of ChinaCorrespondence: Zhengguang Wang, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Email wangzhengguang@ahmu.edu.cnBackground: Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear.Methods: To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results.Results: The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy.Conclusion: Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.Keywords: NFS1, gastric cancer, prognostic biomarker, immune infiltration

Wenyu Zhang,1,&ast; Linquan Li,1,&ast; Yaguang Wu,1 Chengzhilin Li,1 Zi’ang Xu,1 Nianlei Zhang,1 Xinyu Wang,1 Yingchun Zhao,1 Tingjian Zu,1 Qingbin He,1 Jianwei Jiao,2 Runxiao Zheng1 1School of Clinical and Basic Medical Sciences, Medical Science and Technology Innovation Center, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China; 2State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runxiao Zheng, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China, Email zhengrunxiao@sdfmu.edu.cn Jianwei Jiao, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China, Email jwjiao@ioz.ac.cnIntroduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME).Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response.Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy. Keywords: metabolic immunotherapy, nanoparticles, reprograming, iron oxide, macrophages

Chunxia Yin,1,&ast; Taohua Lan,2,3,&ast; Yunshan Wu,4,5 Jing Cai,1 Haoxiang Li,1 Xiaolan Kuang,1 Lin Jiao,1 Xiaomin Ou,1 Hua Yang,2 Bo Liu,3– 5 Weihui Lu2,6,7 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihui Lu, Bo Liu, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Email weihui.lu@gzucm.edu.cn; doctliu@gzucm.edu.cnPurpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification.Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE−/− mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway.Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3β, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3β and NF-κB after MI in ApoE−/− mice.Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE−/− mice.Keywords: network pharmacology, molecular docking, Qushi Huatan decoction, coronary heart disease

Wei Qiang,1,&ast; Mengyi Li,1,2,&ast; Sucai Song,1,3 Ruiqing Dong,1 Tongxin Zhang,1 Xuna Kou,1 Yuan Wu,1 Zhaoxu Wang,1,4 Jiayue Liu,1 Juan Liu,1 Yi Wang,1 Xiaoyan Wu,1 Bingyin Shi,1 Hui Guo1 1Department of Endocrinology and Metabolism, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Endocrinology, Xi’an People’s Hospital, Xi’an, Shaanxi, 710100, People’s Republic of China; 3Department of Endocrinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Endocrinology, Luohe Central Hospital, Luohe, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Guo, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Street, Xi’an, People’s Republic of China, Tel +86-13709292996, Fax +86-029-85323974, Email 13709292996@139.comIntroduction: The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM.Methods: We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles.Results: The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings.Conclusion: The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation.Keywords: T2DM, insulin degludec, glucose variability, insulin initiation

Liying Sun, Xuhui Ye, Junping Yu, Linlin Wang, Yan Wu, Jing Cui, Lihua Dai Intensive Care Unit, Shidong Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Lihua Dai, Intensive Care Unit, Shidong Hospital, Yangpu District, Shanghai, 200438, People’s Republic of China, Tel +86 18917059757, Email gg790516@163.comPurpose: Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) is associated with the prognosis of patients with acute ischemic stroke (AIS); however, the relationship between LMR and early neurological deterioration (END) in AIS patients has not been elucidated.Patients and Methods: Patients were divided into two groups according to LMR by using receiver operating characteristic (ROC) curve analysis. Patients with END were confirmed as the National Institutes of Health Stroke Scale (NIHSS) increased ≥ 4 points between hospital days 0 and 5. Multivariate logistic regression analysis was used to analyze the factors independently related to END in patients with AIS.Results: In total, 202 patients diagnosed with AIS were enrolled in this retrospective study. Using ROC curve analysis, patients were divided into two groups according to LMR: low LMR group (LMR < 3.24, n = 95) and high LMR group (LMR ≥ 3.24, n = 107). The frequencies of END were significantly higher in the low LMR group compared to the high LMR group (41.05 vs.15.89%, p < 0.001). Multivariate logistic regression showed that age (OR = 1.03, 95% CI 1.01– 1.06, p = 0.04), infarct volume (OR = 1.01, 95% CI 1.00– 1.02, p = 0.001), neutrophil count (OR = 1.17, 95% CI 1.03– 1.33, p = 0.018), and LMR (OR = 2.49, 95% CI 1.01– 9.11, p = 0.018) were independently associated with END in AIS patients.Conclusion: A peripheral LMR levels at admission were significantly associated with END and LMR < 3.24 is an independent predictive factor of END in patients with AIS.Keywords: lymphocyte-to-monocyte ratio, acute ischemic stroke, early neurological deterioration, national institutes of health stroke scale

Yang Xu,1,&ast; Yue Wu,1,&ast; Jianhong Liu,2 Lili Xiao,1 Ying Zhang1 1Department of Gastroenterology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhang, Email zhangying750114@163.comBackground: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer.Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests.Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675– 0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744– 0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153– 0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172– 0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer.Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.Keywords: gastric cancer, CDX2, immunoreactivity, chemotherapy, prognostic marker

Junju Zou,1– 3,&ast; Qianbo Song,2,&ast; Pang Chui Shaw,4 Yongjun Wu,1,5 Zhong Zuo,2 Rong Yu1,3 1School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 4School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Yu, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email yurong8072@qq.com Zhong Zuo, School of Pharmacy, the Chinese University of Hong Kong, Hong Kong, SAR, 999077, People’s Republic of China, Email joanzuo@cuhk.edu.hkPurpose: Non-alcoholic fatty liver disease (NAFLD) represents a significant global health burden, exhibiting a strong correlation with insulin resistance, obesity, and type 2 diabetes (T2DM). Despite the severity of hepatic steatosis in T2DM patients, no specific drugs have been approved for clinical treatment of the disease. Tangerine peel is one kind of popular functional food and reported to possess hypoglycemic and lipid-lowering potential. In this study, we investigated the effects of Tangerine-peel-derived exosome-like nanovesicles (TNVs) on hepatic lipotoxicity associated with T2DM.Methods: The TNVs was prepared by differential centrifugation of the aqueous extract of Tangerine and chemical properties were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and LC-MS/MS. The hypoglycemic and lipid-lowering potential of TNVs were possessed by biochemical measurement, RT-PCR, 16S rRNA sequencing, GC/MS, UHPLC-MS/MS, in vivo small animal imaging assay and HE staining. Subsequently, effects of TNVs on lipid accumulation and glycolysis were investigated on 3T3-L1 and AML-12 cells.Results: TNVs significantly inhibited insulin resistance, reduced hepatic lipid accumulation, facilitate intestinal mucosal repair, rescued gut microbiota dysbiosis, regulated colonic SCFA and liver bile acid metabolism in db/db mice. Furthermore, TNVs restored the expression of key genes in glucose and lipid metabolism (ACC, AMPK, CD36, LXRα, PPAR-γ, SREBP-1) while activating the expression of genes related to glycolysis (G6Pase, GLUT2, PCK1, PEPCK) in db/db mice. Further cell-based mechanistic studies revealed that TNVs reduced lipid accumulation in 3T3-L1 and AML-12 cells via regulation of glucose and lipid metabolism-related genes (UCP1, FGFR4, PRDM16, PGC-1α, Tmem26, Cpt1, Cpt2 and PPAR-α).Conclusion: We for the first time demonstrated that TNVs could significantly improve glucose and lipid metabolism via activating the expression of genes related to fatty acid β-oxidation and glycolysis. Keywords: tangerine peel, plant-derived exosome-like nanoparticles, diabetes mellitus, metabolomics, gut microbiota, fat accumulation