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Qiao Xue,1 Jian Peng Pan,2 Da Qian,3 Jie Ji,4 Lai Yi Fei,1 Sheng Yao,1 Xing Tan,1 Wen Ge Fan1 1Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China; 2Department of Hand Surgery, Changshu No. 2 People’s Hospital, The Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu, 215500, People’s Republic of China; 3Department of Burn and Plastic Surgery-Hand Surgery, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China; 4Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of ChinaCorrespondence: Qiao Xue, Department of Dermatology, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People’s Hospital, No. 1 Shuyuan Street, Yushan Town, Changshu, Jiangsu, 215500, People’s Republic of China, Tel +86-13913657476, Email ahjk157@126.com Jian Peng Pan, Department of Hand Surgery, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, 68 South Haiyu Road, Yushan Town, Changshu, Jiangsu, 215500, People’s Republic of China, Tel +86-13814964481, Email 574161036@qq.comObjective: Rosacea is a common chronic inflammatory disorder primarily affecting the face. While inflammatory factors are known to play a pivotal role in its pathogenesis, their causal relationship with rosacea remains unclear. This study employed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal links between systemic inflammatory regulators and rosacea.Methods: Data on 41 cytokines and growth factors were analyzed from a genome-wide association study (GWAS) meta-analysis involving 8293 individuals and genetic data from the FinnGen database, comprising 1195 rosacea cases and 211,139 controls. The principal inverse variance weighting (IVW) method was used to assess causal relationships, with sensitivity analyses, including heterogeneity and horizontal pleiotropy assessments, conducted to ensure result robustness.Results: MR analysis revealed that decreased expression of Stem Cell Factor (SCF), Macrophage Inflammatory Protein-1β (MIP-1β), and Monocyte Chemotactic Protein-1 (MCP-1) was associated with increased rosacea risk (OR = 1.54, 95% CI = 1.05– 2.26, p = 0.026). Conversely, elevated expression levels of Stromal Cell-Derived Factor-1α (SDF-1α) and Hepatocyte Growth Factor (HGF) were linked to higher rosacea risk (OR = 1.61, 95% CI = 1.12– 2.31, p = 0.009). Reverse MR analyses showed no significant impact of rosacea on systemic inflammatory regulator expression.Conclusion: This study identified five inflammatory factors—SCF, SDF-1α, MCP-1, HGF, and MIP-1β—as having causal relationships with rosacea pathogenesis. Further research is required to elucidate their mechanistic roles in disease development.Keywords: rosacea, inflammation, risk, Mendelian randomization, MR, cytokine

Yang Yang,1 Yuanji Zhao,2 Huan Lei,1 Xiaohong Tan3 1College of Physical Education, Chengdu Sport University, Chengdu, Sichuan, 610041, People’s Republic of China; 2School of Physical Education, Wuhan Sports University, Wuhan, Hubei, 430079, People’s Republic of China; 3Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing University of Education, Chongqing, 400067, People’s Republic of ChinaCorrespondence: Yuanji Zhao, School of Physical Education, Wuhan Sports University, Wuhan, Hubei, 430079, People’s Republic of China, Email 2019029@whsu.edu.cnPurpose: When consumed in appropriate quantities, probiotics, which are live microorganisms, are good for health. In this study, a mouse model of antibiotic-induced dyskinesia was established using a sterile mixed antibiotic solution to investigate the preventive impact of Limosilactobacillus fermentum ZS09 (LFZS09) on this condition in mice.Methods: Following modeling, alterations in the serum and brain tissue of mice were assessed for motor measures such as running and swimming, malondialdehyde (MDA), superoxide dismutase, reduced glutathione, interleukin (IL-6, IL-10), and tumor necrosis factor (TNF)-α. The mouse cecum was used to evaluate the relative mRNA expression levels of the intestinal barrier genes, namely occludin-1, zona occludens-1 (ZO-1), and claudin-1. The relative mRNA expression levels of cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) genes in the mouse brain tissue were also evaluated.Results: Compared with the model group, LFZS09 considerably increased the swimming and running duration of mice, significantly decreased the levels of the inflammatory factors TNF-α and IL-6 and increased SOD expression in the mouse brain, and decreased MDA accumulation in the mouse brain and serum. Furthermore, LFZS09 upregulated occludin-1 gene expression in the cecal tissue to maintain the intestinal barrier, which in turn maintained the normal physiological function of the body. LFZS09 also enhanced the effect of BDNF and increased the expression of BDNF metabolic pathway-related genes, namely CREB, ERK1/2, and BDNF, in the mouse brain tissue. LFZS09 increased the number of Lactobacillus and Bifidobacterium in the gut of mice with motor dysregulation, and decreased the number of Enterococcus and Clostridium perfringens.Conclusion: The findings indicate that LFZS09 regulates antibiotic-induced motor impairment in mice, thereby offering a theoretical foundation for future studies and probiotic or parabiotics production aimed at augmenting motor function.Keywords: Limosilactobacillus fermentum, gut function, fatigue, antibiotic, mouse

Doyoung Kwak,1 Yuanjie Liang,2 Xu Shi,3 Xi Tan2 1Department of Electrical & Computer Engineering, Texas A&M University, College Station, TX, USA; 2Novo Nordisk Inc, Plainsboro, NJ, USA; 3Department of Biostatistics, University of Michigan, Ann Arbor, MI, USACorrespondence: Xi Tan, Email mxtz@novonordisk.comPurpose: Observational research provides valuable insights into treatments used in patient populations in real-world settings. However, confounding is likely to occur if there are differences in patient characteristics associated with both the exposure and outcome between the groups being evaluated. One approach to reduce confounding and facilitate unbiased comparisons is inverse probability of treatment weighting (IPTW) using propensity scores. Machine learning (ML) and entropy balancing can potentially be used in generating propensity scores for IPTW, but there is limited literature on this application. We aimed to assess the feasibility of applying these methods for reducing confounding in observational studies. These methods were assessed in a study comparing cardiovascular outcomes in adults with type 2 diabetes and established atherosclerotic cardiovascular disease taking once-weekly glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors.Methods: We applied advanced methods to generate the propensity scores compared to the original logistic regression method in terms of covariate balance. After calculating weights, a weighted Cox proportional hazards model was used to calculate the sample average treatment effect. Support Vector Classification, Support Vector Regression, XGBoost, and LightGBM were the ML models used. Entropy balancing was also performed on features identified in the original cardiovascular outcomes study.Results: Accuracy (range: 0.71 to 0.73), area under the curve (0.77 to 0.79), precision (0.53 to 0.60), recall (0.66 to 0.68), and F1 score (0.60 to 0.64) were similar between all of the advanced propensity score methods and traditional logistic regression. Among ML models, only XGBoost achieved balance in all measured baseline characteristics between the two treatment groups, closely approximating the performance of the original logistic regression. Entropy balancing weights provided the best performance among all models in balancing baseline characteristics, achieving near perfect balancing.Conclusion: Among the advanced methods examined, entropy balancing weights performed the best for optimizing balancing and can produce similar results compared to traditional logistic regression.Keywords: propensity score, machine learning, entropy balancing, type 2 diabetes, glucagon-like peptide-1 receptor agonists

Yijuan Feng,1,* Yan Wang,1,* Li Li,1,* Yan Yang,1 Xiaoqiu Tan,1– 3 Tangting Chen1,2 1Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tangting Chen; Xiaoqiu Tan, Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email ctt@swmu.edu.cn; tanxiaoqiu@swmu.edu.cnAbstract: Recanalization therapy can significantly improve the prognosis of patients with acute myocardial infarction (AMI). However, infarction or reperfusion-induced cardiomyocyte death, immune cell infiltration, fibroblast proliferation, and scarring formation lead to cardiac remodeling and gradually progress to heart failure or arrhythmia, resulting in a high mortality rate. Due to the inability of cardiomyocytes to regenerate, the healing of infarcted myocardium mainly relies on the formation of scars. Cardiac fibroblasts, as the main effector cells involved in repair and scar formation, play a crucial role in maintaining the structural integrity of the heart after MI. Recent studies have revealed that exosome-mediated intercellular communication plays a huge role in myocardial repair and signaling transduction after myocardial infarction (MI). Exosomes can regulate the biological behavior of fibroblasts by activating or inhibiting the intracellular signaling pathways through their contents, which are derived from cardiomyocytes, immune cells, endothelial cells, mesenchymal cells, and others. Understanding the interactions between fibroblasts and other cell types during cardiac remodeling will be the key to breakthrough therapies. This review examines the role of exosomes from different sources in the repair process after MI injury, especially the impacts on fibroblasts during myocardial remodeling, and explores the use of exosomes in the treatment of myocardial remodeling after MI.Keywords: exosomes, myocardial infarction, myocardial fibrosis, cardiac fibroblasts

Shiyu Hu,1,2,* Wenyu Chen,2,* Xiaoli Tan,2,* Ye Zhang,1,2 Jiaye Wang,1,2 Lifang Huang,3 Jianwen Duan4 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Health Management Center, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Hepatobiliary Surgery, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lifang Huang, Health Management Center, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314001, People’s Republic of China, Email jxhuanglifang@126.com Jianwen Duan, Department of Hepatobiliary Surgery, Quzhou People’s Hospital, No. 2, Zhongloudi, Quzhou, Zhejiang, 324000, People’s Republic of China, Email 695377686@qq.comPurpose: The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence.Patients and Methods: This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell’s concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation.Results: In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976– 0.980) for the training set and 0.977 (0.974– 0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all.Conclusion: We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.Keywords: metabolic syndrome, risk factors, nomogram, prediction

Jiaying Cai,1,* Xiyue Tan,2,* Qichao Hu,2,* Huafeng Pan,3 Maoyuan Zhao,4 Cui Guo,4 Jinhao Zeng,1,4,5 Xiao Ma,2 Yanling Zhao6 1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 5Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 6Department of Pharmacy, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinhao Zeng; Yanling Zhao, Email zengjinhao@cdutcm.edu.cn; zhaoyl2855@126.comAbstract: Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances and develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink and other databases to find the relevant literature in the last two decades. Using “gastric cancer”, “stomach cancers”, “flavonoid”, “bioflavonoid”, “ 2-Phenyl-Chromene” as keywords, were searched, then analyzed and summarized the mechanism of flavonoids in the treatment of GC. It was revealed that the anti-tumor mechanism of flavonoids involves inhibiting tumor growth, proliferation, invasion, and metastasis, as well as inducing cell death through various processes such as apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, combining flavonoids with other chemotherapeutic agents like 5-FU and platinum compounds can potentially reduce chemoresistance. Flavonoids have also demonstrated enhanced biological activity when used in combination with other natural products. Consequently, this review proposes innovative perspectives for the development of flavonoids as new anti-GC agents.Keywords: flavonoid, gastric cancer, apoptosis, angiogenesis

Chunxia Jiang,1– 4,&ast; Xiumei Ma,1– 4,&ast; Jiao Chen,2– 5,&ast; Yan Zeng,1– 4 Man Guo,2– 4 Xiaozhen Tan,2– 4 Yuping Wang,1,6 Peng Wang,1 Pijun Yan,2– 4 Yi Lei,1– 4 Yang Long,2– 4 Betty Yuen Kwan Law,1 Yong Xu1– 4 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Third’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 6Department of Breast, Thyroid and Vascular Surgery, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Betty Yuen Kwan Law, Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, People’s Republic of China, Email yklaw@must.edu.mo Yong Xu, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email xywyll@swmu.edu.cnPurpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA).Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P< 0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17– 99% and 0.36, and 24– 99% and 0.24 for the models in normal lactate and high lactate groups, respectively.Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.Keywords: serum lactate, diabetic kidney disease, nomograms, prediction model, risk factors

Jacob T Hall,1 Andrew M Moon,2,3 Michael Young,1 Xianming Tan,3,4 Rami Darawsheh,5 Flora Danquah,3 Joel E Tepper,1,3 Ted K Yanagihara1,3 1Department of Radiation Oncology, University of North Carolina Hospitals, Chapel Hill, NC, USA; 2Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; 3Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC, USA; 4Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; 5University of North Carolina School of Medicine, Chapel Hill, NC, USACorrespondence: Ted K Yanagihara, Department of Radiation Oncology, 101 Manning Drive CB &num;7512, Chapel Hill, NC, 27514, USA, Tel +1-984-974-0400, Email tky@email.unc.eduBackground: We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC).Methods: We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child–Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI.Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5– 388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥ 2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity.Conclusion: Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.Keywords: HCC, SBRT, reirradiation, multi-site, toxicity

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

Li Chen,1,2,&ast; Qiang Liu,2,&ast; Chunlei Tan,3,&ast; Tiangen Wu,4,&ast; Meng Wu,5 Xiaosheng Tan,5 Jinwen Liu,1 Jing Wang2 1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 4Department of Hepatobiliary&Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email wangjing@cicams.ac.cn Jinwen Liu, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email Liujinwen@tjh.tjmu.edu.cnObjective: The current study is conducted to investigate the potential prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in breast cancer patients with liver metastasis after surgery.Methods: This is a retrospective study of 178 breast cancer patients who developed liver metastasis after surgery. These patients were treated and followed up from 2000 to 2018 at our hospital. The aMAP risk score was estimated in accordance with the following formula: . The optimal cutoff value of the aMAP was evaluated via X-tile. Kaplan-Meier, Log-rank and Cox proportional hazards regression models were applied to determine the clinical influence of the aMAP score on the survival outcomes. The nomogram models were established by multivariate analyses. The calibration curves and decision curve analysis were applied to evaluate the estimated performance of the nomogram models.Results: A total of 178 breast cancer patients were divided into low aMAP score group (< 47.6) and high aMAP score group (≥ 47.6) via X-tile plots. The aMAP score was a potential prognostic factor in multivariate analysis. The median disease free survival (p=0.0013) and overall survival (p=0.0003) in low aMAP score group were longer than in high aMAP score group. The nomograms were constructed to predict the DFS with a C-index of 0.722 (95% CI, 0.673– 0.771), and the OS with a C-index of 0.708 (95% CI, 0.661– 0.755). The aMAP-based nomograms had good predictive performance.Conclusion: The aMAP score is a potential prognostic factor in breast cancer with liver metastasis after surgery. The aMAP score-based nomograms were conducive to discriminate patients at high risks of liver metastasis and develop adjuvant treatment and prevention strategies.Keywords: breast cancer, aMAP score, liver metastasis, albumin, prognosis

Ye Zhang,1 Xiaoli Tan,2 Shiyu Hu,3 Zhifang Cui,4 Wenyu Chen2 1Department of General Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Wenyu Chen, Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing City, Zhejiang Province, 314001, People’s Republic of China, Email 00135116@zjxu.edu.cnPurpose: Chronic obstructive pulmonary disease (COPD) concurrent with respiratory failure (RF) is devastating, and may result in death and disability. Systemic immune-inflammation index (SII) is a new prognostic biomarker linked to unfavorable outcomes of acute coronary syndrome, ischemic stroke, and heart failure. Nonetheless, its role in COPD is rarely investigated. Consequently, this study intends to assess the accuracy of SII in predicting the prognosis of COPD.Patients and Methods: The clinical information was retrospectively acquired from the Medical Information Mart for Intensive Care-IV database. The outcomes encompassed the incidence of RF and mortality. The relationship between different SII and outcomes was examined utilizing the Cox proportional-hazards model and restricted cubic splines. Kaplan-Meier analysis was employed for all-cause mortality.Results: The present study incorporated 1653 patients. During hospitalization, 697 patients (42.2%) developed RF, and 169 patients (10.2%) died. And 637 patients (38.5%) died during long-term follow-up. Higher SII increased the risk of RF (RF: HR: 1.19, 95% CI 1.12– 1.28, P< 0.001), in-hospital mortality (HR: 1.22, 95% CI 1.07– 1.39, P=0.003), and long-term follow-up mortality (HR: 1.12, 95% CI 1.05– 1.19, P< 0.001). Kaplan-Meier analysis suggested a significantly elevated risk of all-cause death (log-rank P< 0.001) in patients with higher SII, especially during the short-term follow-up period of 21 days.Conclusion: SII is closely linked to an elevated risk of RF and death in COPD patients. It appears to be a potential predictor of the prognosis of COPD patients, which is helpful for the risk stratification of this population. However, more prospective studies are warranted to consolidate our conclusion.Keywords: systemic immune-inflammation index, chronic obstructive pulmonary disease, respiratory failure, mortality, MIMIC-IV database

Xian Tan,1,2 Hebin Xie,3 Danling Wang1– 3 1Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China; 2Institute for Future Sciences, University of South China, Changsha, Hunan, People’s Republic of China; 3The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Danling Wang, Hengyang Medical School, University of South China, 28 West Changsheng Road, Hengyang, Hunan, 421001, People’s Republic of China, Email danlingwang@usc.edu.cnIntroduction: To reduce unhealthy lifestyles in China, it is critical to implement effective strategies. Counseling provided by physicians is important for assisting patients in improving their lifestyles, and general practitioners (GPs) are the main providers of lifestyle counseling to patients. However, few studies have focused on the lifestyle counseling practices by GPs in China, particularly in regard to nutrition and physical activity.Objective: The aims of this study are: (i) to examine the current practice of Chinese GPs in counseling patients regarding nutrition and physical activity; (ii) to understand the common barriers to such counseling by Chinese GPs; and (iii) to study the association between GPs’ personal lifestyle choices and their practices in lifestyle counseling.Methods: A cross-sectional, self-reported online questionnaire was conducted among GPs in Hunan province, China. A total of 198 GPs completed the questionnaire.Results: The majority of GPs provide nutrition and physical activity counseling to less than 40% of their patients, spending less than three minutes per counseling session. The main reported barriers to counseling on nutrition and physical activity are inadequate time and a lack of knowledge or experience. GPs primarily acquire knowledge through medical books and journals, followed by science popularization. Furthermore, GPs who maintain healthier lifestyle habits, possess a better understanding of lifestyle guidelines, conduct longer office visits, and exhibit higher self-efficacy are more likely to provide counseling to patients.Conclusion: This study highlights the need for improvement in nutrition and physical activity counseling among Chinese GPs. GPs’ personal nutrition and physical activity habits may measurably influence their counseling practice. We recommend that GPs themselves adopt healthier lifestyle habits to potentially improve their counseling practice. Moreover, proactive measures should be taken to assist GPs in overcoming barriers encountered with lifestyle counseling.Keywords: nutrition counseling, physical activity counseling, lifestyle counseling, general practitioner, China

Yihan Sun,1,2 Min Wang,1,2 Xi Tan,1,2 Huidi Zhang,3 Shuang Yang1,2 1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of China; 3Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Shuang Yang, Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of China, Tel +86 15945154368, Email dryangshuang@163.comPurpose: Acute Myocardial Infarction (AMI) is globally prevalent, with oxidative stress as a key contributor to its pathogenesis. This study aimed to explore oxidative stress-related genes as potential AMI biomarkers, elucidating their role in disease progression.Patients and Methods: Gene expression data from AMI samples in the Gene Expression Omnibus (GEO) database and oxidative stress-related genes (OSRGs) from the GeneCards database were extracted. Weighted Gene Co-expression Network Analysis (WGCNA) identified key module genes associated with AMI. Intersecting OSRGs, key module genes, and differentially expressed genes (DEGs) between AMI and normal samples led to the extraction of differentially expressed ORSGs (DE-ORSGs) related to AMI. Feature genes were mined using the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) algorithm, followed by potential diagnostic value assessment using receiver operating characteristic (ROC) curves. Gene Set Enrichment Analysis (GSEA) was executed on the identified key genes. Immune infiltration levels were explored using the CIBERSORT algorithm, and a Transcription Factor (TF) -mRNA regulatory network of key genes was created. The key genes were validated using qRT-PCR.Results: We authenticated three key genes (MMP9, TGFBR3, and S100A12) from 6 DE-ORSGs identified in AMI. GSEA revealed that these key genes were enriched in immune-related signaling pathways. Immune infiltration analysis identified three differential immune cell types (resting NK cells, Monocytes, and M0 Macrophages) between AMI and normal groups. Correlation analysis revealed positive associations of MMP9 with M0 Macrophages and S100A12 with Monocytes and M0 Macrophages, whereas TGFBR3 was negatively related to Monocytes. A TF-mRNA regulatory network was generated based on these key genes. qRT-PCR validation confirmed the differential expression of S100A12 and TGFBR3 between AMI and control samples.Conclusion: TGFBR3, and S100A12 were identified as potential oxidative stress-related biomarkers in AMI, providing new insights for AMI diagnosis and treatment.Graphical Abstract: Keywords: acute myocardial infarction, oxidative stress-related genes, immune infiltration, biomarker

Junzhuo Wang,1,&ast; Ying Tan,1,&ast; Yang Dai,2,3,&ast; Ke Hu,2 Xi Tan,1 Shaoli Jiang,4 Guannan Li,1 Xinlin Zhang,1 Lina Kang,1 Xiaojian Wang,4 Biao Xu1,2 1Department of Cardiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 4Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Xu, Department of Cardiology, the Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Email xubiao62@nju.edu.cn Xiaojian Wang, Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, People’s Republic of China, Email ias_xjwang@njtech.edu.cnPurpose: Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury.Methods: We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan’s Blue and Masson’s staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis.Results: The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced.Conclusion: We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.Graphical Abstract: Keywords: myocardial ischemia-reperfusion injury, extracellular vesicles, hydrogel, intranasal delivery, inflammation

Xuejun Tan,1 Yukun Xu,1 Sirui Zhou,1 Mingyue Pan,1 Yue Cao,1 Xiuping Cai,2 Qing Zhao,1,2,&ast; Kewei Zhao1,2,&ast; 1The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewei Zhao; Qing Zhao, Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, 261 Longxi Avenue, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Tel +86-13711355225 ; +86-18825144487, Email zkw2011@gzucm.edu.cn; zhaoqing900116@126.comAbstract: All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs.Keywords: plant, vesicle-like nanoparticles, inflammation, inflammatory diseases

Kuiliang Li,1 Xiaomei Ren,2 Lei Ren,3 Xuejiao Tan,1 Mengxue Zhao,2 Chang Liu,4 Xi Luo,1 Zhengzhi Feng,2 Qin Dai2 1Department of Medical English, School of Basic Medical Sciences, Army Medical University, Chongqing, People’s Republic of China; 2Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China; 3Department of Clinical Psychology, Air Force Medical University, Xi’an, People’s Republic of China; 4BrainPark, Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Clayton, VIC, AustraliaCorrespondence: Zhengzhi Feng, Department of Medical Psychology, Army Medical University, Chongqing, People’s Republic of China, Tel +86 023-68771480, Email fzz@tmmu.edu.cn Qin Dai, Department of Medical Psychology, Army Medical University, Chongqing, 400038, People’s Republic of China, Tel +86 16623460852, Email daiqin101@hotmail.comBackground: Previous studies have explored the relationship between negative life events and depression, but little is known about the bidirectional relationship between negative life events and depression, particularly in specific groups of medical cadets.Purpose: This study aimed to explore the relationship between negative life events and depressive symptoms among medical cadets during their four years of college.Methods: An analysis of 4-wave longitudinal data collected from 2015– 2018 was conducted using a cross-lagged panel network (CLPN) model to explore the complex causal relationship between negative life events and depressive symptoms in medical cadets (N=433).Results: We found differences in negative life events and depressive symptoms among medical cadets across four network models over four years of university. Nodes A-21, A-20, A-23 and A-24, and depressive symptoms D-6 showed greater lagged effect values.Conclusion: Our findings suggest that there is a lagged and mutually causal interaction between negative life events and depressive symptoms in medical cadets over 4 years of college, but that the predictability of negative life events is more important. However, more attention needs to be paid to the predictive role of depressive symptoms, especially those in early life which are often overlooked. Our study provides new insights into the relationship between negative life events and depressive symptoms in university students and helps to refine strategies for prevention and intervention of depression.Keywords: depression, negative life events, CLPN, longitude relationship, vicious circle, network analysis

Min Xu,1,&ast; Ting Liu,2,&ast; Menghua Ye,1 Xiaoxue Tan,1 Qiuhua Sun2 1The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuhua Sun, Zhejiang Chinese Medical University, The School of Nursing, 548 Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Email sunqiuhua@zcmu.edu.cnBackground: Aplastic anemia is characterized by anemia, hemorrhage and infection, and is accompanied by a variety of complications and psychological burden. Therefore, the quality of life of AA patients is not optimistic. Our team is committed to developing an assessment tool for the quality of life of AA patients, and adopting an iterative strategy of cognitive interview and expert consultation to solve the challenges encountered in item revision.Purpose: We aim to use the strategy of cognitive interview and expert consultation to inform revision of the QLS-AA into a user-friendly tool with unambiguous items and improve the content validity of the scale.Methods: We used an iterative strategy of cognitive interview and expert consultation. Two rounds of cognitive interview were conducted to identify problems with item comprehension, recall and other cognitive processes. As well as, a multi-disciplinary group of expert consultation was consulted to review the rationality of item revisions.Results: In the first round of cognitive interview, 16 participants responded to 107 items. Among them, the most common problems were “clarification” and “item duplication”. Based on the results of the first round of interview, an expert consultation was organized. A total of 16 amendments were put forward by the expert and 14 were adopted. In the second round of cognitive interviews, A total of 5 participants were included and 64 items were evaluated. Two items were suggested to be revised, and the remaining items were accurately understood and recognized by all participants.Couclusion: This study highlights the key issues to consider when incorporating patient perspectives into quality measurement. The revision of QLS-AA through the strategy of cognitive interview and expert consultation may provide valuable insights into the measurement of quality of life in aplastic patients.Trial Registration Number: ChiCTR2100047575.Keywords: cognitive interview, expert consultation, aplastic anemia, quality of life

Xin Tan,1,&ast; Shanling Liu,2,&ast; Li Huang,3 Ying Wu,2 Long Wen,4 Jiheng Liu,5 Yuling Tang,4 Xiaohui Liu6 1Department of Pediatric, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 2Department of Laboratory Medicine, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 3Department of Pharmacy, Zhuzhou Central Hospital, Zhuzhou, 412007, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 5Department of Hematology & Oncology, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China; 6Department of Pharmacy, The First Hospital of Changsha, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohui Liu, The First Hospital of Changsha, Department of Pharmacy, 311 Yingpan Road, Kaifu District, Changsha, 410005, People’s Republic of China, Tel +86 731 84667573, Fax +86 731 84667680, Email gcys2021@126.comPurpose: Long-acting inhalers are the mainstay maintenance therapy for stable chronic obstructive pulmonary disease (COPD) management. The aim of this study was to assess adherence to inhalers among adults with COPD in China and to develop strategies to improve adherence for the next step.Patients and Methods: A cross-sectional study was conducted among 246 adult patients with COPD using long-acting inhalers to explore different demographic characteristics, disease characteristics and medication regimens. Adherence to inhalers was assessed using the Medication Adherence Report Scale (MARS).Results: Among the 246 patients included in the present study, 93 (37.80%) had good adherence, while 153 (62.20%) had poor adherence. From the comparison of patients with good and poor adherence, we found that the course of disease and education background had a significant effect on adherence (p < 0.05). Among the LAMA therapy group, inhaled tiotropium bromide spray (Ingelheim am Rhein, Germany) with active release technology had better adherence than inhaled tiotropium bromide powder (Ingelheim am Rhein, Germany) (p < 0.05). Moreover, COPD patients with good adherence had better pulmonary function and fewer moderate or severe exacerbations in the past year (p < 0.05).Conclusion: The factors affecting the use of inhalers in patients with stable COPD are complicated. Medical staff should select appropriate inhalers according to the patient’s disease status and duration and provide medication education to improve adherence.Keywords: chronic obstructive pulmonary disease, inhalers, adherence, duration of illness

Xin Tan, Wenjie Liu, Ying Chang, Wanmin Wu, Lichun Yang, Jiewei Liu Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Jiewei Liu, Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-13834648535, Email Jieweiliu1967@sina.comPurpose: The safety and stability of implantable collamer lens (ICL) implantation are closely related to the vault. We aimed to assess clinical data from patients with similar anterior segment anatomy who received ICL of the same model placed in the same position and analyze common range and factors affecting the vault inter-eye difference.Patients and Methods: A prospective study was performed, including 162 eyes of 81 patients with a bilateral ICL (V4c) implantation. Subjects were evaluated before the surgery and 1 day, 1 week, and 1 month postoperatively, and they were divided into 4 groups based on the ICL size. Bivariate correlation and multiple linear regression (stepwise) analyzed associations between vault inter-eye differences and horizontal sulcus-to-sulcus diameter, anterior chamber depth, lens thickness, ICL size, spherical equivalent, and vault.Results: One month after surgery, mean vault inter-eye differences were 74.59 ± 55.59 μm. Nearly 70% of patients presented with vault inter-eye differences lower than 100 μm. The second eye vault variance of 69% was attributed to the first eye vault. Vault inter-eye differences were positively correlated with ICL spherical equivalent (regression equation: vault inter-eye differences (μm) = 139.415 + 6.295 × ICL spherical equivalent). Vaults after ICL implantation were similar in fellow eyes, with some considerable differences. The 95% confidence interval of the vault inter-eye difference was − 34.4 ~ 183.6 μm.Conclusion: In eyes with similar anterior segment anatomy, there is a 95% probability that the vault will vary from − 34.4 μm to − 183.6 μm when a similar ICL is implanted. These results can help surgeons to select an appropriate ICL size to achieve an ideal vault. The smaller the spherical equivalent, the larger the difference between the two vaults, which provides a reference for size in moderate myopia. ICL spherical equivalent affects and predicts vault inter-eye differences after ICL implantation.Keywords: implantable collamer lens, vault, inter-eye differences

Huan Zhang,1,2 Xiaojiao Tan,1 Zhen Zhang,1 Xuewei Yang,1 Lijie Wang,1 Meiqian Li,1 Dan Shi,1 Yao Li,1 Jianbo Li,1 Zhen Li,3 Xuelian Liao1,4 1Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Critical Care Medicine, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 3Clinical Research Unit, First Maternity and Infant Hospital of Shanghai, Shanghai, People’s Republic of China; 4Department of Critical Care Medicine, West China Tianfu Hospital of Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xuelian Liao, Department of Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou district, Chengdu, People’s Republic of China, Tel +8613541023033, Email liaoxuelian@scu.edu.cnPurpose: To assess the impact of targeted antibiotic therapy on clinical outcomes of patients with lower respiratory tract (LRT) infection with Corynebacterium striatum (C. striatum).Methods: A new propensity score-inverse probability of treatment weighting (IPTW) cohort study was conducted by using 10-year data. The study included LRT infection patients with respiratory secretions cultured positive for C. striatum simultaneously. The primary outcome was all-cause hospital mortality; the secondary outcomes included hospital stay, ICU stay and ventilation time. The safety outcomes were drug-related serum creatinine (Cr) increase and thrombocytopenia.Results: A total of 339 patients were included in the cohort, and 84 (24.78%) initiated vancomycin or linezolid therapy. In the new IPTW cohort, targeted antibiotic therapy did not improve all-cause hospital mortality (P=0.632), and the OR (95% CI) was 0.879 (0.519– 1.488). Moreover, targeted antibiotic therapy was not associated with hospital stay (P=0.415), ICU stay (P=0.945) or ventilation time (P=0.885). The side effects of drug-related higher serum Cr (P=0.044) and thrombocytopenic levels (P=0.038) cannot be ignored.Conclusion: Clinical benefits by vancomycin or linezolid targeted against LRT infection with C. striatum were limited and with drug-related side effects. A prospectively designed study is needed to further confirm the results.Keywords: Corynebacterium striatum, lower respiratory tract infection, vancomycin, linezolid, all-cause mortality

Junhui He,1,&ast; Dongbo Han,2,&ast; Chunlian Jia,2,&ast; Jiaxiu Xie,1 Fucui Zhu,2 Jie Wei,1 Dongmei Li,1 Dongmei Wei,1 Yi Li,1 Li Tang,3 Guining Wei,1,4 Jing Yan,4 Yuanming Tong,1 Lifang Yang,4,&ast; Xuecai Tan4,&ast; 1Department of Pharmacology, Key Laboratory of Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, 530022, People’s Republic of China; 4Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, 530008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuecai Tan; Lifang Yang, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning, 530008, People’s Republic of China, Tel +86 0771-5877473, Email gxunxctan@126.com; yanglf1990@163.comPurpose: To investigate the mechanisms of antidepressant action of active fraction of Polyrhachis vicina Rogers (AFPR) through network pharmacology, molecular docking and experimental validation.Methods: GC-MS was used to predict chemical compounds, corresponding databases were used to predict chemical compound targets and depression targets, Cytoscape software was used to construct and analyze the protein interaction network map, DAVID database was used to analyze gene ontology (GO) and KEGG signaling pathway, and AGFR software was used to perform molecular docking. Subsequently, the underlying action mechanisms of AFPR on depression predicted by network pharmacology analyses were experimentally validated in a CORT-induced depression model in vitro and in vivo.Results: A total of 52 potential targets of AFPR on antidepressant were obtained. GO is mainly related to chemical synaptic transmission, signal transduction and others. KEGG signaling pathways are mainly related to cAMP signaling pathway and C-type lectin receptor signaling pathway. The experiment results showed that AFPR significantly increased the expression of PRKACA, CREB and BDNF in mouse brain tissue and PC12 cells. Furthermore, after interfered of cAMP in PC12 cells, the decreased expression of PRKACA, CREB and BDNF was reversed by AFPR.Conclusion: AFPR may exert antidepressant effects through multiple components, targets and pathways. Furthermore, it could improve neuroplasticity via the cAMP signaling pathway to improve depression-like symptoms.Graphical Abstract: Keywords: PC12 cells, BDNF, corticosterone, CAMP signaling pathway, GC-MS

Ruojing Qian,1– 3,&ast; Zhaoyu Xu,4,&ast; Xingyu Hu,1– 3 Suru Liu,1– 3 Yao Mai,1– 3 Xinzhi Tan,1– 3 Xiaofan Su,1– 3 Mingyan Jiang,1– 3 Wei Tang,1– 3 Weidong Tian,1– 3 Li Xie1– 3 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Tian; Li Xie, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85502156 ; +86-28-85503499, Email drtwd@sina.com; samuel@163.comPurpose: A synergistic antibacterial system employing photocatalytic performance and low-temperature photothermal effect (LT-PTT) with the potential for infectious skin wound healing promotion was developed.Methods: Ag/Ag2O was synthesized with a two-step method, and its physicochemical properties were characterized. After its photocatalytic performance and photothermal effect were evaluated under 0.5 W/cm2 808 nm NIR laser irradiation, its antibacterial activities in both planktonic and biofilm forms were then studied in vitro targeting Staphylococcus Aureus (S. aureus), and the biocompatibility was tested with L-929 cell lines afterward. Finally, the animal model of dorsal skin wound infection was established on Sprague-Dawley rats and was used to assess infectious wound healing promotion of Ag/Ag2O in vivo.Results: Ag/Ag2O showed boosted photocatalytic performance and local temperature accumulation compared with Ag2O when exposed to 0.5 W/cm2 808 nm NIR irradiation, which therefore endowed Ag/Ag2O with the ability to kill pathogens rapidly and cleavage bacterial biofilm in vitro. Furthermore, after treatment with Ag/Ag2O and 0.5 W/cm2 808 nm NIR irradiation, infectious wounds of rats realized skin tissue regeneration from a histochemical level.Conclusion: By exhibiting excellent NIR-triggered photocatalytic sterilization ability enhanced by low-temperature photothermal effect, Ag/Ag2O was promising to be a novel, photo-responsive antibacterial agent.Keywords: semiconductor/metal hybrid, antibacterial agent, photo-responsive antibacterial activity, reactive oxygen species, infectious wound skin model

Yuan Ma, Jing Li, Xinyue Tan, Mengjiao Cai, Xiaozhi Zhang,&ast; Jinlu Ma&ast; Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinlu Ma; Xiaozhi Zhang, Email majinlu@xjtufh.edu.cn; zhangxiaozhi@xjtu.edu.cnBackground: Individual survival prediction is of vital importance to optimize the individualized treatment of metastatic cervical cancer (mCC) patients. The goal of this study was to identify the potential risk factors for the survival of mCC patients and construct a nomogram for their prognosis.Methods: Medical records of patients with newly diagnosed mCC at the First Affiliated Hospital of Xi’an Jiaotong University were reviewed retrospectively. Risk factors were identified using Cox proportional hazards analysis and Kaplan–Meier curves. Random forest was used to identify factors associated with therapy strategy. Nomogram and dynamic nomogram were established using ‘rms’ and “DynNom” R package.Results: A total of 98 patients with mCC were finally identified. In Cox analyses, multiple metastases and concurrent chemoradiotherapy (CCRT) were identified as independent predictors for overall survival (OS). We further explored the prognostic value of metastatic number and sites and therapy strategies for mCC patients by Kaplan–Meier curves. A dynamic nomogram including metastases number and sites (multiple metastases, liver and lymph node (LN) above diaphragm metastases) and chemoradiotherapy strategies (CCRT, postradiotherapy chemotherapy, and radiotherapy to metastatic sites) was constructed for predicting the prognosis of mCC patients. For newly diagnosed patients, we strongly recommended the combination of chemotherapy and definitive pelvic radiotherapy and, if possible, radiation to metastatic site, but CCRT should be implemented with caution. We constructed a dynamic nomogram indicating that patients with younger age, shorter symptom duration, and better laboratory test results are suitable for CCRT.Conclusion: Survival analyses showed that the metastatic number and sites and therapy strategies are associated with the prognosis of mCC patients. The CCRT and prognostic nomograms may help clinicians to make better clinical decisions and effectively predict the prognosis for newly diagnosed mCC patients.Keywords: metastatic cervical cancer, nomogram, multiple metastases, concurrent chemoradiotherapy, real world

Yanli Ren,1 Bin Chen,2 Jiaying Zhao,3 Xiaohua Tan,1 Xinyi Chen,2 Lin Zhou,2 Fei Wang,2 Ying Peng,2 Jianmin Jiang1,2 1School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Zhejiang Center for Disease Control and Prevention, Hangzhou, People’s Republic of China; 3School of Public Health, Xiamen University, Fujian, People’s Republic of ChinaCorrespondence: Ying Peng; Jianmin Jiang, Email ypeng@cdc.zj.cn; jmjiang@cdc.zj.cnObjective: To understand the trend of overall rifampicin resistance rates for tuberculosis in Zhejiang Province between 2015 and 2019.Methods: The basic demographic information of patients with tuberculosis who were screened for drug resistance in Zhejiang Province between January 1, 2015 and December 31, 2019 was collected through the national Tuberculosis Information Management System. The data were processed and analyzed using IBM SPSS 26.0 and GeoDa 1.14 software.Results: The total rifampicin resistance rate was 5.9% in 53,893 validated cases of drug resistance screening conducted in patients with pulmonary tuberculosis in Zhejiang Province during the study period. There was a decreasing trend in the rifampicin resistance rate in both initial and re-treated patients (P< 0.001), but the rifampicin resistance rate was higher in re-treated TB patients than in TB patients receiving their initial treatment (11.4% vs 4.2%). The rate of drug resistance steadily decreased in all prefectures, and there was a significant upward trend in the use of the Xpert MTB/RIF rapid assay. An increasing trend was also identified in the rate of rifampicin and ofloxacin co-resistance (P< 0.001).Conclusion: The overall rate of rifampin resistance in patients with tuberculosis in Zhejiang Province in the past five years has shown a decreasing trend, but the rate of resistance to ofloxacin was high. Resistance testing to fluoroquinolones should be carried out as early as possible in patients whose diagnosis results indicate rifampin resistance, and more effective second-line treatment plans should be developed based on the results of this testing.Keywords: rifampicin, drug-resistant tuberculosis, ofloxacin, trend analysis

Dafei Wei1 &ast;, Qi Wang2 &ast;, Shasha Liu,2 Xiaowu Tan,2 Lin Chen,2 Rongfang Tu,2 Qing Liu,2 Yuanhang Jia,2 Sha Liu2 1Department of Pediatrics, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sha Liu, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China, Email 2018020001@usc.edu.cnObjective: To explore the clinical effects of different forced expiratory volume in 1s (FEV1) reference equations on chronic obstructive pulmonary disease (COPD) airflow limitation (AFL) classification.Methods: We conducted a COPD screening program for residents over 40 years old from 2019 to 2021. All residents received the COPD screening questionnaire (COPD-SQ) and spirometry. Postbronchodilator FEV1/FVC (forced vital capacity) < 0.7 was used as the diagnostic criterion of COPD and two reference equations of FEV1 predicted values were used for AFL severity classification: the European Respiratory Society Global Lung Function Initiative reference equation in 2012 (GLI-2012) and the Guangzhou Institute of Respiratory Health reference equation in 2017 (GIRH-2017). Clinical characteristics of patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) 1– 4 grades classified by the two reference equations were compared.Results: Among 3524 participants, 659 subjects obtained a COPD-SQ score of 16 or more and 743 participants were found to have AFL. The COPD-SQ showed high sensitivity (59%) and specificity (91%) in primary COPD screening. Great differences in COPD severity classification were found when applying the two equations (p < 0.001). Compared with GIRH-2017, patients with AFL classified by GLI-2012 equations were significantly severer. The relationship between symptom scores, acute exacerbation (AE) history distributions and COPD severities classified by the two equations showed a consistent trend of positive but weak correlation. Group A, B, C and D existed in all GOLD 1 to 3 COPD patients, but in GOLD 4, only Groups B and D existed. However, no clear significant differences were found in symptoms, AE risk assessments, risk factors exposure and even the combined ABCD grouping under the two equations.Conclusion: There were significant differences in COPD AFL severity classification with GLI-2012 and GIRH-2017 FEV1 reference equations. But these severity estimation differences did not affect symptoms, AE risk assessments and ABCD grouping of patients at all GOLD grades.Keywords: COPD, airflow limitation, FEV1%pred, symptoms assessment, acute exacerbation

Min Yu,1,2,* Jiacheng Zhong,1,2,* Xueyong Bu,3,* Xinjuan Tan,1,2 Danting Zhan,1,2 Xiaoyi Hu,1 Yingying Gu,4 Jing Xu,5 Peize Zhang,6 Lingwei Wang1,2 1Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, 518055, China; 2Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518055, China; 3Department of Radiology, Shenzhen Longgang District Maternity & Child Healthcare Hospital, Shenzhen, 518172, China; 4Department of Pathology, Guangzhou Institute of Respiratory Health, Guangzhou, 510120, China; 5Department of Pathology, Shenzhen People’s Hospital, Shenzhen, 518055, China; 6Department of Pulmonary Medicine & Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, China*These authors contributed equally to this workCorrespondence: Lingwei Wang, Email limey1212@163.comCase Presentation: The patient was a middle-aged housewife who had been using the household spray for a long time, and the main symptoms were cough and sputum production. Chest CT showed lobar ground-glass opacities (GGOs) with small patchy consolidation in the right middle lobe (RML), specifically, lung tissue pathology showed a large number of foamy cells and scattered multinucleated giant cells. The patient received empirical anti-infective treatment, but no clinical improvement was observed. Laboratory tests, including smears and cultures of sputum, blood and bronchoalveolar lavage fluid (BALF), did not provide clear evidence for pathogenic microorganisms. Therefore, the presumptive diagnosis was exogenous LP (ExLP). After 28 days of prednisone treatment, her symptoms improved, but 2 months later, she presented with a worsening cough, and the GGOs had progressed into lobar consolidation. Transbronchial lung biopsy (TBLB) culture showed mycobacterium tuberculosis (MTB), and lung tissue pathology showed granulomatous inflammation. After anti-tuberculosis treatment, the consolidation in the right middle lobe was gradually absorbed, along with a considerable symptom improvement. The final diagnosis of the patient was MTB infection with an endogenous lipoid pneumonia (EnLP)-like presentation.Conclusion: The current case highlights that the MTB infection should be considered when pathology shows LP accompanied by scattered multinucleated giant cells.Keywords: mycobacterium infection, aetiology, pathological diagnosis

Xiaoqi Tan,1,&ast; Yuxin He,1,&ast; Yongliang Ou,2 Xia Xiong,1 Yongqiong Deng1 1Department of Dermatology STD, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Health Management Center, Luzhou People’s Hospital, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqiong Deng; Xia Xiong, Department of Dermatology STD, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan Province, People’s Republic of China, Email dengyongqiong1@126.com; xiongxia789@126.comPurpose: Taohong Siwu decoction (THSWD) is traditionally used to treat androgenic alopecia (AGA) in clinical practice of traditional Chinese medicine. This study used a network pharmacology approach to elucidate the molecular mechanism governing the effect of THSWD on AGA.Materials and Methods: The major active components and their corresponding targets of THSWD were screened. AGA-related targets were obtained by analyzing the differentially expressed genes between AGA patients and healthy individuals. The protein–protein interaction networks of putative targets of THSWD and AGA-related targets were visualized and merged to identify the candidate targets for THSWD against AGA. Gene ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for core targets were performed. Finally, the key effective components and core targets screened were verified by molecular docking.Results: In this study, 69 compounds and 202 compound targets of THSWD, as well as 1158 disease targets, were screened. Forty-five interactive targets were identified for constructing the “ingredient-targets” network. The functional annotations of target genes were found to be related to oxidative stress, reactive oxygen species, and hydrogen peroxide. Pathways involved in the treatment of AGA included apoptosis and PI3K-AKT signaling pathways. The luteolin, quercetin, kaempferol, baicalein, and beta-carotene were identified as the vital active compounds, and AKT1, TP53, JUN, CASP3 and MYC were considered as the core targets. Assessment of molecular docking revealed that these active compounds and targets had good-binding interactions.Conclusion: The results indicated that the effects of THSWD against AGA may be related to anti-inflammation and anti-oxidation properties of the compounds through the specific biological processes and the related pathways.Keywords: Taohong Siwu decoction, network pharmacology, mechanism prediction, androgenetic alopecia