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Qian Cheng,1 Yishu Tang,2 Jing Liu,1 FeiYang Liu,1,&ast; Xin Li1,&ast; 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: FeiYang Liu; Xin Li, Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China, Tel +86-731-88618814 (88618214) ; Tel +86-731-88618814 (88618214), Email 546917399@qq.com; lixiner1975@163.comObjective: The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections.Methods: Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed.Results: Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2– 4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients.Conclusion: CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Clinical Relevance Statement: Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Keywords: pneumonia, hematological malignancies, computed tomography, diagnostic value

XingYun Liu,1,&ast; JingDuo Zhao,2,&ast; FuRong Liu,1 ZhiZhong Xie,2 XiaoYong Lei,2 Zhe Wang,3 Zerui Yang,4 YuSheng Zhou,1,3 GuoTao Tang2 1The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 2Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, People’s Republic of China; 3The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4NMPA Key Laboratory for Technology Research and Evaluation of Pharmacovigilance, Guangdong Pharmaceutical University, Guangzhou, 510086, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YuSheng Zhou, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email yszhou08@126.com GuoTao Tang, Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, Hengyang, Hunan, 421001, People’s Republic of China, Email tgtzq@163.comBackground: Breast cancer treatment has been a global puzzle, and targeted strategies based on the hypoxic tumor microenvironment (TME) have attracted extensive attention. As a signature transcription factor overexpressed in hypoxia tumor, hypoxia-inducible factor-1 (HIF-1) contribute to cancer progression. Compound 7-(3-(2-chloro-1H-benzo[d]1midazole-1-yl) propoxy)-2-(3,4,5-trime-thoxyphenyl)-4H-chromen-4-one, synthesized and named FB15 in our earlier research, a potential inhibitor of HIF-1α signaling pathway, has been proved a promising drug candidate for many kinds of cancer chemotherapy. However, the poor solubility and undesirable pharmacokinetics of FB15 leads to limited treatment efficacy of tumor, which ultimately restricts its potential clinical applications. Carbonic anhydrase IX (CAIX), a tumor cell transmembrane protein, was overexpressed in hypoxia tumor site. Acetazolamide (AZA), a highly selective ligand targeting CAIX, can be utilized to delivery FB15 to hypoxia tumor site.Methods: In this study, we prepared and characterized FB15 loaded nano-mixed micelles with the AZA conjugated poloxamer 188 (AZA-P188) and D-a-Tocopherol Polyethylene 1000 Glycol Succinate (TPGS), denoted as, AZA-P188/TPGS@FB15. Its delivery efficiency in vitro and in vivo was assessed by in vitro drug release, cytotoxicity assay, cellular uptake, and in vivo pharmacokinetics and fluorescence imaging. Finally, therapeutic effect of AZA-P188/TPGS@FB15 was investigated using a preclinical breast cancer subcutaneous graft model in vivo.Results: In vitro studies revealed that AZA-P188/TPGS@FB15 could efficiently target breast cancer cells mediated by CAIX receptor, trigger FB15 release in response to acidic condition, and enhance cellular uptake and cytotoxicity against breast cancer cells. The pharmacokinetic studies showed that FB15-loaded AZA-functionalized micelles exhibited significantly increased AUC0-t over free FB15. In vivo imaging demonstrated that AZA-functionalized micelles significantly increased the drug distribution in the tumor site. In vivo experiments confirmed that AZA-P188/TPGS@FB15 exhibited superior inhibition of tumor growth in nude mice with good biosafety.Conclusion: AZA-P188/TPGS@FB15 hold promise as a potentially effective therapeutic way for breast cancer. Its targeted delivery system utilizing AZA as a carrier shows potential for improving the efficacy of FB15 in cancer therapy.Keywords: carbonic anhydrase IX-targeting, FB15, hypoxia inducible factor-1, nano-mixed micelles, pH-responsive

Haoran Li,1 Xi Chen,2 Hui Feng,1 Fangyi Liu,3 Jie Yu,1 Ping Liang1 1Department of Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Ultrasound, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 3Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jie Yu; Ping Liang, Department of Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email jiemi301@163.com; liangping301@126.comPurpose: The diagnosis of liver abscess (LA) caused by Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB) depends on ultrasonography, but it is difficult to distinguish the overlapping features. Valuable ultrasonic (US) features were extracted to distinguish GPB-LA and GNB-LA and establish the relevant prediction model.Materials and Methods: We retrospectively analyzed seven clinical features, three laboratory indicators and 11 US features of consecutive patients with LA from April 2013 to December 2023. Patients with LA were randomly divided into training group (n=262) and validation group (n=174) according to a ratio of 6:4. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve(AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group.Results: A total of 436 participants (median age: 55 years; range: 42– 68 years; 144 women) were evaluated, including 369 participants with GNB-LA and 67 with GPB-LA, respectively. A total of 11 predictors by LASSO regression analysis, which included gender, age, the liver background, internal gas bubble, echogenic debris, wall thickening, whether the inner wall is worm-eaten, temperature, diabetes mellitus, hepatobiliary surgery and neutrophil(NEUT). The performance of the Nomogram prediction model distinguished between GNB-LA and GPB-LA was 0.80, 95% confidence interval [CI] (0.73– 0.87). In the validation group, the AUC of GNB was 0.79, 95% CI (0.69– 0.89).Conclusion: A model for predicting the risk of GPB-LA was established to help diagnose pathogenic organism of LA earlier, which could help select sensitive antibiotics before the results of drug-sensitive culture available, thereby shorten the treatment time of patients.Keywords: liver abscess, Gram-positive bacteria, Gram-negative bacteria, ultrasonography features, prediction model

Tianqing Cao,1,&ast; Fei Liu,2,&ast; Yan Yao,2 Danghong Sun,2 Rong Wang,3 Junxia Cao,3 Jie Meng,2 Ling Zhang,4 Weiming Li1 1Shanghai Tenth People’s Hospital, Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Pulmonology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 4Department of Nursing, Changshu No.2 People’s Hospital/Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiming Li; Ling Zhang, Email 18917683469@189.cn; nancy120312@163.comObjective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI.Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC).Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy.Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.Keywords: myocardial infarction, frailty index, major adverse cardiac events, prognosis, cohort study

Xu Tian,1,&ast; Fangrong Liu,2,&ast; Feili Li,3 Yi Ren,4 Hongcai Shang5 1Chongqing Center for Evidence-Based Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 2Outpatient Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 4Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Ren, Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 6 of 7th Branch of Panxi Road, Jiangbei District, Chongqing, People’s Republic of China, Tel/Fax +86 023 67776180, Email cqszyyrenyi@163.com Hongcai Shang, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 of Haiyuncang, Dongcheng District, Beijing, People’s Republic of China, Tel/Fax +86 010 84013276, Email yxtx880919@163.comPurpose: While the benefits of exercises for chronic obstructive pulmonary disease (COPD) are well-established, the relative effectiveness of different exercise types for stable COPD remains unclear. This network meta-analysis aims to investigate the comparative effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in stable COPD.Methods: Electronic searches were performed in PubMed, Embase, and the Cochrane library to identify relevant randomized controlled trials (RCTs) investigating the effects of exercises on 6-minute walk test distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC), and St. George’s Respiratory Questionnaire (SGRQ) score. Two authors screened the retrieved articles, extracted relevant data, and assessed the risk of bias. Network meta-analysis was conducted using Stata 14.0.Results: This study included a total of 19 studies involving 951 patients with stable COPD. HIIT emerged as the most favorable exercise type for enhancing 6MWD, with a probability of 82.9%. RT exhibited the greatest efficacy in reducing SGRQ scores, with probability of 49.8%. Notably, ET demonstrated superiority in improving FEV1 and FVC, with probabilities of being most effective at 78.1% and 42.0%, respectively.Conclusion: This study suggests that HIIT may be a viable intervention for improving exercise capacity in stable COPD patients, compared to AE, RR, and ET. RT may hold promise for improving quality of life, and ET may demonstrate superiority in improving pulmonary function. However, variation in response likely depends on patient characteristics, program parameters, and delivery context. Future research should explore the synergistic effects of combining RT with ET/HIIT, focusing on patient subgroups, optimal dosing, and settings, as current guidelines indicate this combination may offer the most significant benefits.Keywords: COPD, exercise, pulmonary function, quality of life, network meta-analysis

Tianlong Li,&ast; Nana Hou,&ast; Lili Mao, Fangmei Liu, Zilong Ma, Li Wang, Xiyue Xu, Guanghui Yan, Yujia Han, Jinxian Wei Department of Gynecology, Zhengzhou First People’s Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinxian Wei, Email 13700887408@163.comBackground: Although there are many benign tumors in the ovarian adnexal area, the four most common types are still luteal cyst, ovarian mature cystic teratoma (OMCT), ovarian endometriosis, and benign epithelial tumors of the ovary.Purpose: This study aimed to examine the correlation between six tumor markers (CEA, AFP, CA125, CA19-9, SCC, HE4) in the differential diagnosis of female adnexal benign masses and assess their diagnostic value.Patients and Methods: In this study, 135 patients with adnexal benign masses were treated in Zhengzhou first people’s Hospital from January 2018 to January 2023. 135 patients were divided into four groups: luteal cyst (13.3%), OMCT (42.2%), ovarian endometriosis (23.7%) and benign epithelial tumors of the ovary (including mucinous cystadenoma and serous cystadenoma) in group D. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection.Results: The diameter of luteal cysts was significantly smaller than that of benign ovarian tumors (p < 0.001). ROC analysis showed that the combination of AFP, CA125, CA19-9, and SCC had a higher diagnostic rate for luteal cysts (AUC=0.871; sensitivity: 71.8%; specificity: 88.9). The SCC level in OMCT was significantly higher than in other benign ovarian tumors (p=0.007). ROC analysis indicated that the combination of AFP, HE4, and SCC had a higher diagnostic rate for OMCT (AUC=0.753; sensitivity: 65.4%; specificity: 75.4%). The CA125 level in ovarian endometriosis was significantly higher than in other accessory benign tumors (p < 0.001). ROC analysis demonstrated that the combination of AFP, CA125, and CA19-9 had a higher diagnostic rate for ovarian endometriosis (AUC=0.935; sensitivity: 76.7%; specificity: 96.9%). The tumor diameter of benign epithelial tumors of the ovary was significantly larger than that of other benign ovarian tumors (p < 0.001). ROC analysis revealed that the combination of CA125 and CA19-9 had a higher diagnostic rate for benign epithelial tumors of the ovary (AUC=0.792; sensitivity: 64.5%; specificity: 85.7%).Conclusion: The findings of this study demonstrate that the combined use of tumor markers (CEA, AFP, CA125, CA19-9, SCC, and HE4) has value in diagnosing benign ovarian tumors, including luteal cysts, OMCT, ovarian endometriosis, and benign epithelial tumors of the ovary. However, it is important to acknowledge the limitations of this study, which include its single-center nature and the small sample size. Despite these limitations, the results highlight the potential utility of these markers in clinical practice.Keywords: luteal cyst, OMCT, ovarian endometriosis, ovarian epithelial benign tumors, tumor markers

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Kang He,1,&ast; Jie Zang,2,&ast; Tingting Ren,1,&ast; Shaojie Feng,3 Mohan Liu,1 Xude Zhang,3 Wenchang Sun,2 Jinjin Chu,2 Donghua Xu,2 Fengxia Liu3 1Department of Clinical Medicine of Shandong Second Medical University, Weifang, People’s Republic of China; 2Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University/Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Allergy, Weifang People’s Hospital, Shandong Second Medical University, Weifang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghua Xu; Fengxia Liu, Email flower322@163.com; wf_lfx@163.comAbstract: Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.Keywords: atopic dermatitis, mesenchymal stem cells, Th2-associated immunity, extracellular vesicle

Gongjie Zhang,1 Xinlyu Huang,1 Hanlin Li,1 Huizi Gong,1 Yabin Zhou,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Yabin Zhou, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, No. 56 Nan Lishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10 59616884, Email chouyabin@163.com Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti Nan Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 18611369216, Email roseliufang@qq.comBackground: Hair loss is common in hypothyroidism patients. However, the link with alopecia areata (AA) and androgenetic alopecia (AGA) is unclear. Previous observational studies have presented completely opposite results. This study aims to causally link hypothyroidism with AA and AGA.Methods: A two-sample Mendelian Randomization (MR) study, utilizing data from FinnGen Consortium, investigated the causal link between hypothyroidism and AA and AGA. We employed Inverse Variance Weighted (IVW), MR-Egger, Weighted Median, Simple Mode, and Weighted Mode to assess the risk association.Results: The discovery samples included 13,429 hypothyroidism cases (94,436 controls), 767 alopecia areata cases (394,105 controls), and 220 androgenetic alopecia cases (219,249 controls). MR analysis showed a causal link between hypothyroidism and AA, with significant results from IVW (OR, 1.34; CI, 1.16– 1.56; P = 0.0001), MR-Egger (OR, 1.56; CI, 1.09– 2.23; P = 0.0240), and weighted median (OR, 1.34; CI, 1.06– 1.69; P = 0.0140). However, no clear causal relationship was found between genetically predicted hypothyroidism and AGA risk (p > 0.05).Conclusion: The results show hypothyroidism causally associated with AA onset, but not AGA. These findings address contentious issues in observational studies. Comprehensive thyroid function assessments are crucial for AA patients, emphasizing thorough clinical examinations’ importance.Keywords: hypothyroidism, alopecia areata, androgenetic alopecia, Mendelian randomization study, causality

Hao Kang,1,2,&ast; Fansu Meng,3,&ast; Fengjie Liu,4 Mengjie Xie,4 Haibiao Lai,3 Pengfei Li,5 Xingwang Zhang4 1Department of Medicinal Chemistry and Pharmaceutical Analysis, Anhui College of Traditional Chinese Medicine, Wuhu, People’s Republic of China; 2Wuhu Modern Technology Research and Development Center of Chinese Medicine and Functional Food, Wuhu, People’s Republic of China; 3Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, People’s Republic of China; 4Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 5Department of Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibiao Lai; Xingwang Zhang, Email lhb8829@163.com; zhangxw@jnu.edu.cnAbstract: Ferroptosis, a unique form of regulated cell death driven by iron-dependent lethal lipid peroxidation, is implicated in various stress-related diseases like neurodegeneration, vasculopathy, and metabolic disturbance. Stress-related diseases encompass widespread medical disorders that are influenced or exacerbated by stress. These stressors can manifest in various organ or tissue systems and have significant implications for human overall health. Understanding ferroptosis in these diseases offers insights for therapeutic strategies targeting relevant pathways. This review explores ferroptosis mechanisms, its role in pathophysiology, its connection to stress-related diseases, and the potential of ferroptosis-targeted nanomedicines in treating conditions. This monograph also delves into the engineering of ferroptosis-targeted nanomedicines for tackling stress-related diseases, including cancer, cardia-cerebrovascular, neurodegenerative, metabolic and inflammatory diseases. Anyhow, nanotherapy targeting ferroptosis holds promise by both promoting and suppressing ferroptosis for managing stress-related diseases.Keywords: ferroptosis, stress-related diseases, lipid peroxidation, nanoparticles, nanomedicine, targeted therapy

Tao Chen,1– 3,&ast; Yumeng Wei,1– 3,&ast; Suyu Yin,1– 3,&ast; Wen Li,1– 3 Yuxiang Wang,1– 3 Chao Pi,1– 3 Mingtang Zeng,3,4 Xiaodong Wang,5 Ligang Chen,6 Furong Liu,7 Shaozhi Fu,8 Ling Zhao2,3 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; Luzhou, Sichuan, 646000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China, Tel +86 830 2681630, Email zhaoling@swmu.edu.cnPurpose: The present study aimed to develop a lipid nanoplatform, denoted as “BAL-PTX-LN”, co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs.Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining.Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration.Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications. Keywords: baicalin derivative, paclitaxel, chemotherapy, lung cancer, lipid nano platform, combination therapy

Xinlyu Huang,1 Pengxiang Zhao,2 Gongjie Zhang,1 Xiangxi Su,1 Hanlin Li,1 Huizi Gong,1 Xuemei Ma,2 Fang Liu1 1Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2College of Chemistry and Life Science, Beijing University of Technology, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Venereology and Cosmetology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email roseliufang@qq.comPurpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration.Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines.Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration.Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation.Keywords: alopecia, hair regrowth, non-pharmacologic, gas therapy, regenerative cellular therapy, laser therapy, microneedle therapy

Luo-Gang Ding,1,&ast; Xiang Ji,2,&ast; Yue-Yue Liu,3,&ast; Min Shi,1 Jian-Da Li,1 Fei Liu,1 Yu-Yu Zhang,1 Jiang Yu,1 Jia-Qiang Wu1 1Shandong Key Laboratory of Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Shandong Microbial Engineering, College of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 3Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan, 250100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Qiang Wu; Jiang Yu, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China, Email yujiang_2213@163.com; wujiaqiang2000@sina.comBackground: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection.Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe.Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival.Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.Keywords: crystal porous materials, microenvironment-responsive, controlled release, fluorescence imaging, diagnosis and therapy

Benchi Cai,&ast; Qitong Wang,&ast; Lifan Zhong, Fang Liu, Xinyu Wang, Tao Chen Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Chen, Email chentao@hnyxy15.wecom.workBackground: Parkinson’s disease (PD) is the most prevalent movement disorder. Curcumin, a polyphenol with hydrophobic properties, has been proved against Parkinson. Our previous study suggested that curcumin’s effectiveness in treating Parkinson’s disease may be linked to the gut-brain axis, although the specific mechanism by which curcumin exerts neuroprotective effects in the brain remains unknown.Methods: The therapeutic efficacy of curcumin was evaluated using behavioral tests, immunofluorescence of tyrosine hydroxylase (TH). Network pharmacology and transcriptomics predicted the mechanisms of curcumin in PD. Activation of the phosphatidylinositol 3-kinase PI3K/AKT pathway was confirmed by quantitative polymerase chain reaction (qPCR) and immunofluorescence.Results: Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson’s disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway.Conclusion: In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson’s disease was revealed by our study.Keywords: Parkinson’s disease, curcumin, network pharmacology, transcriptomics, PI3K / AKT pathway

Li Zhang,1,&ast; Mupeng Li,1,&ast; Lianlian Fan,1 Fangfang Liu,1 Peiwen Zhang,1 Qian Huang,1 Gang Mai,1 Jianzhong Shentu1,2 1Phase 1 Clinical Trial Center, Deyang People′s Hospital, Deyang, Sichuan, People’s Republic of China; 2Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Shentu, Email stjz@zju.edu.cn Gang Mai, Email stdygcp@163.comPurpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions.Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method.Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80– 125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study.Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.Keywords: bioequivalence, estradiol valerate, postmenopausal, pharmacokinetics, safety

Xingyuan Li,1,2,&ast; Fenghao Yang,3,&ast; Nan Li,4,&ast; Yong Xu,5 Fang Liu1,2 1Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Kidney Research Institute, Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Psychiatry, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Liu, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comBackground: Diabetic kidney disease (DKD) patients require comprehensive disease education and mutual support to cope with various challenges. Social media platforms provide opportunities for DKD patients to access information and interact with peers. However, qualitative analysis of DKD patients’ real-world concerns and needs on social media is lacking.Methods: A qualitative study was conducted to analyze DKD patients’ posts on Facebook and Baidu DKD-specific forums from June 2013 to June 2023. Posts were retrieved, and the forum with the most DKD-related posts from each platform was selected using stratified random sampling. Thematic analysis was performed to identify common themes, which were categorized and quantified.Results: In total, 746 DKD-related posts were analyzed, generating 203 keyword categories with 954 tags. Three main themes emerged: Diagnosis and Comorbidities (50.2%), Treatment and Prevention (29.7%), and Lifestyle and Psychology (20.1%). Patients were most concerned about DKD diagnosis, staging, comorbidities, and interpreting diagnostic indicators. They also sought information on treatment advancements, medications, renal replacement therapies, and traditional Chinese medicine. Diet, exercise, work-life balance, family planning, and mental well-being were key lifestyle and psychological concerns.Conclusion: This study reveals DKD patients’ primary needs and concerns on social media, which can guide healthcare professionals in providing targeted education and support. Meeting patients’ needs through comprehensive education and counseling can improve treatment adherence and prognosis, though challenges remain in addressing all issues in real-world practice.Keywords: diabetic kidney disease, qualitative research, patient education, social media

Shengling Hu, Qi Yu, Fenfang Liu, Fengyun Gong Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of ChinaCorrespondence: Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China, Email 2020jy0008@hust.edu.cnBackground: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients.Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD.Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM.Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.Keywords: tuberculosis-associated obstructive pulmonary disease, systemic inflammatory response index, ratio inflammatory indicator, propensity score matching

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Siyu Fan,1,&ast; Yu Zhao,1,&ast; Shiyu Wang,1,&ast; Na Zhang,1,&ast; Zhi Li,1,&ast; Hongyuan Liu,1 Yaodi Wei,1 Yunhui Yu,1 Yifeng Gu,2 Qun Wei,3 Weijuan Ye,4 Ninghan Feng,5 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Surgical Oncology, Institute of Clinical Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Lishui Maternal and Child Health center, Lishui, Zhejiang, People’s Republic of China; 5Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ninghan Feng, Department of Urology, Jiangnan University Medical Center, Wuxi, Jiangsu, 214002, People’s Republic of China, Email n.feng@njmu.edu.cn Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnAim: This study aims to explore the psychological reactions of medical students during the pandemic.Design: A qualitative study.Methods: A purposive sampling technique was employed, and a qualitative approach was adopted. Semi-structured questionnaires were utilized, and online interviews were conducted. Forty medical students were selected as participants for the interviews. The interview data were analyzed using Colaizzi’s seven-step analysis method.Results: The study identified five themes related to the psychological reactions of medical students during the pandemic. Firstly, COVID-19’s influence on medical careers was characterized by increased interest and determination in pursuing medical professions, heightened admiration for frontline workers, reinforced commitment to a medical career due to the pandemic, and recognition of the significance of medical education. Secondly, challenges and concerns in medical career pursuit were identified, including negative sentiments towards medical careers during COVID-19 and hesitations and concerns about entering the medical field amidst the pandemic. Thirdly, the impact on mental well-being encompassed diverse anxieties expressed by participants regarding control, transmission, treatment, and intentional spreading of the virus. Participants experienced an emotional progression from calmness to fear and anxiety, with heightened anxiety when relatives or acquaintances contracted COVID-19. Academic delays also contributed to anxiety among medical students. Fourthly, changes in behaviors and mindset were observed, including altered behaviors and mindset in response to the pandemic, as well as increased attention to personal hygiene and disease prevention measures. Lastly, expectations of medical students from government, public, and parents were explored.Conclusion: Understanding the psychological reactions of medical students during public health emergencies is crucial for their well-being and professional development. The findings have implications for medical education and the development of strategies to enhance the psychological well-being of medical students during similar crises.Keywords: COVID-19, medical students, psychological reactions, pandemic, mental health

Hongyuan Liu,1,&ast; Yaodi Wei,1,&ast; Zhenyi Xu,2,&ast; Hao Lin,2,&ast; Yu Zhao,1 Shiyu Wang,1 Fengbao Gao,1 Ninghan Feng,2 Alan J Wolfe,3 Fengping Liu1 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Urology, Affiliated Wuxi No. 2 Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA&ast;These authors contributed equally to this workCorrespondence: Alan J Wolfe, Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA, Email awolfe@luc.edu Fengping Liu, Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China, Email liulaoshiyc@jiangnan.edu.cnPurpose: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.Patients and Methods: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.Results: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients’ decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients’ decisions to pursue fecal microbiota transplantation; (3) the patients’ perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.Conclusion: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.Registration: CHiCTR2100048970.Keywords: barriers, decision making, facilitators, fecal microbiota transplantation, qualitative study, recurrent urinary tract infections

Fengyao Liu,1,2,&ast; Haochen Wang,2,3,&ast; Bingqing Bai,2,4 Han Yin,5 Yuting Liu,2 Yu Wang,2 Quanjun Liu,2 Shuxia Wang,6 Huan Ma,3 Qingshan Geng1,2,5 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 5Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 6Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Ma, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, People’s Republic of China, Fax +8620-83827812, Email mahuandoctor@163.com Qingshan Geng, Department of Cardiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), 1080 Cuizhu Road, Luohu District, Shenzhen, Guangdong, Fax +0755-25533018, Email gengqsh@163.netPurpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200– 9.681), P = 0.021).Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.Keywords: obstructive sleep apnea, mental stress induced myocardial ischemia, angina with no obstructive coronary artery disease, myocardial perfusion imaging

Qian Xie,1,&ast; Chang Liu,1,&ast; Fen Liu,2 Xuehe Zhang,1 Zhiyang Zhang,1 Xin An,1 Yining Yang,3– 6 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, People’s Republic of China; 4Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, Urumqi, People’s Republic of China; 5State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, People’s Republic of China; 6Key Laboratory of Cardiovascular Disease Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: Metabolic Syndrome (MS) greatly increases the risk of heart disease and Heart Failure(HF). Insulin Resistance (IR) is considered to be the key to the pathophysiology of MS. The purpose of this study was to evaluate the predictive effect of different alternative indicators of IR on adverse cardiovascular events in patients with MS complicated with HF.Methods: Patients with HF who were diagnosed with MS in the heart center of the first affiliated Hospital of Xinjiang Medical University were selected continuously. The baseline data of the patients in the group were compared. The diagnostic value of alternative indexes of IR was evaluated by the working characteristic curve of subjects. The relationship between different alternative indicators of IR and survival rate was evaluated by survival curve. COX regression was used to analyze the effects of different alternative indicators of IR on the risk of end-point events.Results: The levels of TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR were significantly increased in patients with Major Adverse Cardiovascular Events (MACEs). Among the five alternative indexes of IR, METS-IR had the highest AUC (0.691, 95% CI:0.657– 0.752, P < 0.001) in predicting MACEs. No matter which alternative index of IR was used, the survival rate of MACEs in High group was significantly decreased. TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR can independently predict the occurrence of MACEs events, even if some confounding factors are adjusted.Conclusion: Our study shows that alternative indicators of IR, especially METS-IR, are independently associated with adverse cardiovascular events in patients with MS and HF.Keywords: insulin resistance indexes, metabolic syndrome, heart failure, predictive

Xiaojing Wu,1,2 Xiaosong Gai,1,2 Hongyang Kou,3 Lili Xu,1 Fangqing Liu,4 Hong Wang1 1School of Psychology, Northeast Normal University, Changchun, Jilin Province, People’s Republic of China; 2Research Center of Mental Health Education in Northeast Normal University, Key Research Institute of Humanities and Social Science in Universities in Jilin Province, Changchun, Jilin Province, People’s Republic of China; 3Northeast Asian Studies College, Jilin University, Changchun, Jilin Province, People’s Republic of China; 4Institute of Mental Health, NanJing Xiaozhuang University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xiaosong Gai, School of Psychology, Northeast Normal University, No. 5268, Renmin Street, Changchun, Jilin Province, People’s Republic of China, Email gaixs669@nenu.edu.cnPurpose: Life satisfaction can predict students’ school engagement and academic performance, and has shown significant regional differences among adolescents. The predictive effect of economic factors as regional characteristics on adolescent life satisfaction has been extensively examined; however, the regional educational factors that could predict adolescent life satisfaction remain unknown. This study aimed to identify provincial-level educational factors that can predict adolescent life satisfaction.Methods: The participants comprised 16,737 students, aged 11– 16 years (Mage = 13.82; SDage = 0.77; 8767 girls, 7970 boys), from 31 provinces in China. Students completed measures on socioeconomic status and life satisfaction. Multilevel modeling was adopted in data analysis.Results: Adolescent life satisfaction was positively correlated with family socioeconomic status, and negatively associated with age and academic ranking. Life satisfaction was lower for girls than boys. Some regional education development indicators could predict adolescent life satisfaction: ratio of students to teachers, ratio of students to teachers with master’s degrees, and multimedia classroom size negatively correlated with adolescent life satisfaction; meanwhile per capita sports field area positively correlated with adolescent life satisfaction. Per capita education expenditure, classroom area, laboratory area, computer room area, language lab area, gymnasium area, green space area, sports field area, computers per student, number of books, and value of equipment and instruments could not significantly predict life satisfaction in this study.Conclusion: The findings suggest that the life satisfaction of female adolescents, those in older age groups, with lower academic rankings and socioeconomic status, and those residing in regions with underdeveloped educational systems was relatively poor. These groups of adolescents should therefore be given special attention. To enhance their life satisfaction, some certain provinces should consider implementing measures such as increasing the number of teachers, reducing class sizes, and providing more opportunities for physical activity among junior middle school students.Keywords: provincial-level, junior middle school students, life satisfaction, education, ecological systems theory

Hongmei Yang,1,&ast; Zhongqi Liu,1,&ast; Fan Liu,1,2,&ast; Haixuan Wu,1 Xiaoyan Huang,1 Rong Huang,1 Phei Er Saw,3,4 Minghui Cao1,2 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Department of Anesthesiology, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Shanwei, 516600, People’s Republic of China; 3Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Phei Er Saw; Minghui Cao, Email caipeie@mail.sysu.edu.cn; caomh@mail.sysu.edu.cnBackground: Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia.Methods: To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA.Results: Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine (p < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group (p < 0.0001).Conclusion: Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.Keywords: lipid nanoparticle, Tet1, peripheral nerve-targeted, pain management, chronic neuropathic pain

Yuwei Ma,1,2,&ast; Tao Jiang,1,2,&ast; Rong Zhang,1 Fei Liu,3 Shilong Song,1,2 Huijun Zhang,4 Jingwen Huang,1 Zelai He1,2 1The First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 3Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 4Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zelai He; Jingwen Huang, Email hezelai@alumni.sjtu.edu.cn; he.ze.lai@163.com; byyfyhjw@163.comIntroduction: Lung cancer’s high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy.Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections.Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments.Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.Keywords: 2D Mxene, drug delivery system, hydrogel, lung cancer

Fang Liu,1,&ast; XuYong Yang,2,&ast; Zhaohui He,1 Chenghong OuYang,1 Xiaogang Yang,1 Chunli Yang1 1Department of Intensive Care Unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China; 2Department of Pediatrics, Gaoxin Hospital of The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Yang; Chunli Yang, Department of intensive care unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China, Email JXSRMICU@163.com; 434533590@qq.comBackground: In addition to the well-known Whipple’s disease (WD), Tropheryma Whipplei (TW) can also lead to acute pneumonia. There is no unified consensus on the susceptible population, pathogenesis, clinical manifestations, diagnostic criteria, and treatment options for TW pneumonia.Clinical Presentation and Intervention: This is an elderly patient with multiple injuries caused by falling from a building, and was transferred to intensive care unit (ICU) for mechanical ventilation and empirical anti-infection treatment due to severe pneumonia, and then the results of targeted next-generation sequencing (tNGS) in patient’s bronchoalveolar lavage fluid (BALF) suggested TW and human metapneumovirus (HMPV) infection, and after switching to anti-infective therapy for TW, the patient was successfully extubated and transferred out of the ICU.Conclusion: This is the first case of using tNGS to diagnose severe pneumonia caused by TW and HMPV. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.Keywords: Tropheryma Whipplei, bronchoalveolar lavage fluid, targeted next-generation sequencing, human metapneumovirus

Haitang Qiu,1,&ast; Shajidan Abudureyimu,1,&ast; Mengjia Liu,1 Fen Liu,2 Ying Gao1 1Department of Comprehensive Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Clinical Medical Research, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Comprehensive Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, Xinjiang, 830054, People’s Republic of China, Tel +86-991-4362625, Email gaoydct@163.comObjective: This study was conducted to investigate the combined effect of genetic variation in the C3 gene and environmental factors on the risk of type 2 diabetes mellitus(T2DM) and coronary artery disease(CAD) in a population from Xinjiang, China.Methods: We conducted a hospital-based case-control study with 896 participants (217 with T2DM+CAD and 679 healthy controls). A polymerase chain reaction-ligase detection reaction was used to identify and genotype TagSNPs in the C3 gene, and the influence of the interaction of two SNP loci (rs1047286 and rs11569562) with the environment on T2DM combined with CAD was evaluated through clinical data, statistical analysis of gene frequencies, and the formation of a gene-environment interaction model.Results: We find that rs11569562 GG is an independent protective factor for T2DM and CAD (OR=0.353, p=0.012), and the variants at its locus may be closely associated with Activated Partial Thromboplastin Time (APTT), lipoprotein a (Lp(a)), Apolipoprotein A (APOA), Aspartate Aminotransferase (AST), Aspartate Aminotransferase (ALT) and AST/ALT levels (all P < 0.05); its GG genotype has significantly lower Gensini score and number of stenoses than the GA and AA genotypes. Multifactorial dimensionality reduction (MDR) finds a strong correlation between rs11569562 and AST (antagonistic effect) (4.44%); the role of rs11569562’s influence remains strong in terms of the independent effects of each attribute (1.72%).Conclusions: In this study, we find that variants in the C3 gene loci rs11569562 are associated with the incidence of type 2 diabetes mellitus combined with coronary heart disease in a Chinese population. It is expected to be an independent predictor of type 2 diabetes mellitus combined with coronary heart disease in the Chinese population. Rs11569562 may be associated with lipid levels and coagulation molecules.Clinical Trial Registration: This trial registered on in 2014 at the China Clinical Trials Registry (ChiCTR-TRC-14005114).Keywords: coronary heart disease, Type 2 diabetes mellitus, complement C3

Nan Liu, Jinlei Dong, Lianxin Li, Dongsheng Zhou, Fanxiao Liu Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Fanxiao Liu, Department of Orthopedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324, Road Jing Wu Wei Qi, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-15069058755, Email woshi631@126.comAbstract: Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl’s clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.Keywords: osteolysis, bone resorption, bone loss, Metrnl, arthritis, stiff elbow

Gengyao Hu,1,&ast; Yuanhang Pan,1,&ast; Na Yuan,1,&ast; Zhixian Yang,2 Xiuyu Shi,3 Sha Ma,4 Shan Li,4 Xiaohua Hou,5 Fei Liu,5 Dongmei Li,6 Junxiang Bao,7 Yonghong Liu1 1Department of Neurology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 2Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Pediatrics, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 4Department of Neurology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6Department of Dentistry for Special Services, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 7Department of Aerospace Hygiene, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Email liuyhong@fmmu.edu.cnBackground: Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM.Methods: Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed.Results: The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic.Conclusion: SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.Keywords: sleep-related facial mandibular myoclonus, tongue biting, movement disorder, SRFMM

Fan Liu,1,&ast; Huan Yu,1,&ast; Qing Xu,2,&ast; Jianwei Gong,1 Ming Huo,3,4 Fei Huang1,3 1School of Health and Life Sciences, Binzhou Medical University, Yantai, People’s Republic of China; 2Yaitai Hospital, Binzhou Medical University, Yantai, People’s Republic of China; 3School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4Beijing Chaoyang Sanhuan Cancer Hospital, Beijing, 100122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Huo, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, 17 Shandong Road, Qingdao, 266071, People’s Republic of China, Email huoming8@gmail.com Fei Huang, School of Health and Life Sciences, Binzhou Medical University, 346 Guanhai Road, Laishan, Shandong Province, 264003, People’s Republic of China, Email hfei22518@163.comPurpose: Falls are a significant factor affecting the health of older adults and are closely related to cognitive function. Adopting an effective method to evaluate the risk of falls in older adults is essential for improving their healthcare. This study combined cognitive and motor functions to determine a reliable probe reaction time during water-carrying walking.Patients and Methods: We divided 100 community-dwelling older adults (aged 65 years and over) into two groups according to their fall history: the fall group and no-fall group. All subjects were tested on fall tasks using the timed up-and-go (TUG) test, 10-m walk timing test, trail marking test part-A (TMT-A), and water-carrying walking probe reaction time (P-RT).Results: The fall group showed slower walking speeds and longer TUG, TMT-A, and P-RT times than the no-fall group. In the logistic regression analysis with falls as the dependent variable, water-carrying walking P-RT was identified as a useful factor, and the cut-off value of the water-carrying walking P-RT was 454 ms, which was evaluated using the receiver operating characteristic curve.Conclusion: The P-RT of the water-carrying walking test was found to be credible and useful for evaluating the fall risk in older adults. Therefore, it is recommended that the P-RT-based dual-task be used as a predictive indicator of future falls in the older population.Keywords: falls, probe reaction time, older adults, dual task

Feiyang Liu,1 Huicun Duan,2 Yongqing Hou,3 Bohua Zhang,3 Jinlong Wu,1 Liya Guo1 1School of Physical Education, Southwest University, Chongqing, People’s Republic of China; 2Research Center of Psychology and Social Development, Southwest University, Chongqing, People’s Republic of China; 3Faculty of Psychology, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Liya Guo, School of Physical Education, Southwest University, Tiansheng Road, Beibei District, Chongqing, People’s Republic of China, Email 974634029@qq.comPurpose: The deleterious impact of aggressive behavior on college students necessitates urgent mitigation. To explore the influencing factors and underlying mechanisms of aggressive behaviors among college students, this study aims to validate the mediating roles of life satisfaction, meaning in life, and depression by examining the relationship between physical exercise and aggressive behaviors among college students.Methods: The Physical Activity Rating Scale-3 (PARS-3), Satisfaction with Life Scale, Meaning in Life Questionnaire, Chinese Version DASS-21 and 12-item Perception of Aggression Scale (POAS) were tested on 1596 college students from three universities in western China, and SPSS 26.0 and Mplus 8.3 were used for analysis.Results: Physical exercise exhibited a significant negative correlation with both aggressive behaviors and depression among college students (r = – 0.57, P < 0.001; r = – 0.36, P < 0.001), as well as a significant positive correlation with life satisfaction and meaning in life (r = 0.45, P < 0.001; r = 0.27, P < 0.001). Regarding the impact of physical exercise on aggressive behaviors among college students, the mediating effects of life satisfaction, meaning in life, and depression were significant. The respective effect sizes were − 0.11, − 0.08, and − 0.03. The chain mediation effect of life satisfaction through depression was also found to be significant, with an effect size of − 0.02.Conclusion: This study elucidates the mechanistic pathways through which physical exercise influences aggressive behavior among college students. The relationship between physical exercise and aggressive behavior is influenced by the individual mediating effects of life satisfaction, meaning in life, and depression, as well as the chain mediation effect of life satisfaction through depression. These findings provide a novel perspective on the prevention and intervention of aggressive behaviors among college students in China and potentially worldwide. This suggests that more attention should be paid to the organic combination of students’ physical activity and mental health education.Keywords: physical exercise, life satisfaction, meaning in life, depression, aggressive behavior

Fengbo Liu,1 Yue Xi,2 Ning Li,3 Ming Wu4 1School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai, People’s Republic of China; 3School of Physical Education, Putian University, Putian, Fujian Province, People’s Republic of China; 4Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Fengbo Liu, School of Physical Education, Zhengzhou University of Light Industry, Zhengzhou, Henan Province, People’s Republic of China, Email lfbzzuli@126.comObjective: To explore the impact of brief mindfulness training on college students’ mobile phone addiction and the mediating effect of the sense of meaning in life between them.Methods: This study has employed the mixed experimental design of 2 (experimental conditions) × 2 (time points), randomly assigned 44 college students into a mindfulness training group and a control group (22 college students in each group), and selected the Freiburg Mindfulness Inventory (FMI), Mobile Phone Addiction Tendency Scale (MPATS), and Chinese Meaning in Life Questionnaire (C-MLQ) to conduct separate tests before and after mindfulness training.Results: The results show that: (1) in the pretest, the differences between the mindfulness training group and the control group in the level of mindfulness, the level of mobile phone addiction, and the sense of meaning in life are not statistically significant; (2) in the posttest, compared with those of the control group, both the FMI score (p=0.013) and the C-MLQ score (p< 0.001) of the mindfulness training group improve significantly, while the MPATS score (p=0.008) of the mindfulness training group declines significantly; and (3) the Bootstrap analysis of the mediating effect shows that after the change in C-MLQ (95% CI [0.537, 11.630]) enters the equation, the direct effect of mindfulness training is not significant (95% CI [− 3.254, 5.861]).Conclusion: The results of this study reveal the impact and mechanism of brief mindfulness training on college students’ mobile phone addiction, and provide an empirical basis for intervening on mobile phone addiction.Keywords: brief mindfulness, mobile phone addiction, sense of meaning in life, mediating effect

Rui Zhao,1 Feng Liu,1 Kun Zhu2,3 1Department of General Practice Medicine, Bengbu Medical University, Bengbu, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China; 3Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Kun Zhu, Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Bengbu, Anhui, 233000, People’s Republic of China, Tel +86-18755271096, Email zk19870128@163.comBackground: The competencies of college senior students in general practice medicine have attracted attention. This study aimed to construct an evaluation index system of competencies for college senior students in general practice medicine and to promote the reform and optimization of training programs for general medicine talent in colleges.Methods: The two-round Delphi method was used to determine the evaluation index system of competencies for college senior students in general practice medicine, and the analytic hierarchy process (AHP) was used to calculate the weights of all levels of elements.Results: The evaluation index system of competencies for college senior students in general practice medicine was established with 3 primary factors, 9 secondary factors and 32 tertiary factors. The Delphi results revealed that the active coefficient of experts was 1 and the authority coefficient was 0.858. The 3 primary factors were knowledge level, job skills and professionalism with weights of 0.1532, 0.4207 and 0.4261, respectively. Among the secondary factors, the top three weight coefficients were professional ethics (0.2614), community practice (0.1526) and communication skills (0.1308). Among tertiary factors, “scientific research” exhibited the lowest value with a weight coefficient of 0.0049.Conclusion: In this study, we constructed an evaluation index system of competencies for college senior students in general practice medicine. The consensus on the content of the competencies of college senior students in general practice medicine suggests that these elements are necessary for those who will become general practitioners. This system can be used as the basis to evaluate the ability of college senior students in general practice medicine and provide guidance for the cultivation and evaluation of general medicine talent.Keywords: evaluation index system, competencies, college senior students, general practice medicine

Jing Li,1,&ast; Na Zhu,2,&ast; Yaqiong Wang,2 Yanlei Bao,3 Feng Xu,2 Fengjuan Liu,2 Xuefeng Zhou2 1Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, Qingdao, People’s Republic of China; 3Department of Pharmacy, Liaoyuan People’s Hospital, Liaoyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuefeng Zhou, Clinical Trial Research Center, Affiliated Qingdao Central Hospital of Qingdao University, Qingdao Central Hospital, No. 127, Siliunan Road, Shibei District, Qingdao, Shandong, 266042, People’s Republic of China, Tel +86 18561856181, Email zhouxuefeng5019@163.comAbstract: Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.Keywords: metabolomics, traditional Chinese medicine, type 2 diabetes mellitus, diabetic complications, diagnosis

Fengyu Liu,1,2,&ast; Huajing Chang,1,&ast; Xiaojun Liu1,3 1School of Public Health, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2School of Public Health, National Key Laboratory of Health Technology Assessment (National Health Commission of the People’s Republic of China), Global Health Institute, Fudan University, Shanghai, People’s Republic of China; 3School of Health Management, Provincial Research Center for Healthcare Reform and Development of Fujian, Health Research Institute, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Liu, School of Health Management, Fujian Medical University, No. 1 Xuefu North Road, University New District, Fuzhou City, Fujian Province, 350122, People’s Republic of China, Tel + 86 591-22869579, Email xiaojun_liu@fjmu.edu.cnBackground: Non-adherence or partial adherence is the main reason for poor therapeutic effect of hypertension. This paper aims to assess adherence behaviors and related factors among elderly hypertensive patients in China.Methods: Participants aged ≥ 60 years, with hypertension, and with complete data in 2018 interviews of the China Health and Retirement Longitudinal Study (CHARLS) were included. The adherence behaviors included medication, blood pressure monitoring and the combined adherence behaviors. Referring to the social-ecological theory, correlates of adherence behaviors were divided into three layers, namely demographic characteristics, health behaviors, living environment and retirement. Univariate and multivariable logistic regression models were performed to identify factors of adherence behaviors.Results: The prevalence of medication adherence (76.58%) was higher than that of blood pressure monitoring adherence (20.08%), and the full adherence rate was 18.53%. Self-rated health status, smoking status, living area, and health education status were detected to be associated with medication adherence and blood pressure monitoring adherence (all p < 0.05). Gender, sleep duration, health examination, and physical exercise were also detected to be associated with blood pressure monitoring adherence (all p < 0.05). Self-rated health status and health education status were detected to be associated with partially and fully adherence, while age, living area, and life satisfaction were detected to be associated with partially adherence, smoking status, sleep duration, health examination, and pension reliance were detected to be associated with fully adherence (all p < 0.05).Conclusion: Our study reveals the poor adherence behaviors of elderly hypertensive patients in China. This is most evident among those who were male, 60– 69 years old, living in rural areas, self-reported being healthier, those without health examination and health education. Targeting these vulnerable populations, we suggest to strengthen health education, increase the publicity of basic public health services and enhance the self-management ability of hypertensive patients.Keywords: medication adherence, blood pressure monitoring, hypertension, behavior, elderly

Rui Zhang,1 Weixuan Sheng,2 Feiran Liu,1 Jin Zhang,1 Wenpei Bai1 1Department of Obstetrics and Gynaecology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenpei Bai, Email baiwp@bjsjth.cnObjective: This study aimed to investigate the risk factors of cesarean section and establish a prediction model for cesarean section based on the characteristics of pregnant women.Methods: The clinical characteristics of 2552 singleton pregnant women who delivered a live baby between January 2020 and December 2021 were retrospectively reviewed. They were divided into vaginal delivery group (n = 1850) and cesarean section group (n = 702). These subjects were divided into training set (2020.1– 2021.6) and validation set (2021.7– 2021.12). In the training set, univariate analysis, Lasso regression, and Boruta were used to screen independent risk factors for cesarean section. Four models, including Logistic Regression (LR), K-Nearest Neighbor (KNN), Classification and Regression Tree (CART), and Random forest (RF), were established in the training set using K-fold cross validation, hyperparameter optimization, and random oversampling techniques. The best model was screened, and Sort graph of feature variables, univariate partial dependency profile, and Break Down profile were delineated. In the validation set, the confusion matrix parameters were calculated, and receiver operating characteristic curve (ROC), precision recall curve (PRC), calibration curve, and clinical decision curve analysis (DCA) were delineated.Results: The risk factors of cesarean section included age and height of women, weight at delivery, weight gain, para, assisted reproduction, abnormal blood glucose during pregnancy, pregnancy hypertension, scarred uterus, premature rupture of membrane (PROM), placenta previa, fetal malposition, thrombocytopenia, floating fetal head, and labor analgesia. RF had the best performance among the four models, and the accuracy of confusion matrix parameters was 0.8956357. The Matthews correlation coefficient (MCC) was 0.753012. The area under ROC (AUC-ROC) was 0.9790787, and the area under PRC (AUC-PRC) was 0.957888.Conclusion: RF prediction model for caesarean section has high discrimination performance, accuracy and consistency, and outstanding generalization ability.Keywords: caesarean section, machine learning, confusion matrix, univariate partial dependence profile

Zhe Sun,1,&ast; Ruijie Zhou,2,&ast; Jinjin Dai,2,&ast; Jihua Chen,2 Yu Liu,2 Mengyi Wang,2 Runlong Zhou,2 Fengchen Liu,2 Qinxing Zhang,3 Yao Xu,2 Tongcun Zhang1,2 1College of Biotechnology, Tianjin University of Science and Technology, Tianjin, People’s Republic of China; 2Institute of Biology and Medicine, College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Wuhan Bio-Raid Biotechnology Co., Ltd, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xu; Tongcun Zhang, Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, No. 2 Huangjiahu West Road, Wuhan, Hubei, 430081, People’s Republic of China, Tel +86-027-68897343, Fax +86-027-68893590, Email xuyao0307@wust.edu.cn; zhangtongcun@wust.edu.cnBackground: Ovarian cancer (OV) is the highest prevalent gynecologic tumor with complicated pathogenesis; high-grade serous ovarian cystadenocarcinoma (HGSOC) is the most epidemiological and malignant subtype of OV. Keratin type I cytoskeleton 19 (KRT19) is an intermediate filament protein which plays essential roles in the maintenance of epithelial cells. However, its role in OV remains largely unknown.Methods: Bioinformatic analysis with various databases was conducted in this study. In details, KRT19 expression was assessed using databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA). GO-KEGG and GSEA analysis were performed by R packages. The biological function of KRT19 was analyzed based on the single-cell sequencing information from CancerSEA database. The association of KRT19 expression with immunomodulator and chemokine was predicted via the TISIDB database.Results: The expression of KRT19 was significantly upregulated in ovarian samples compared with normal controls. KRT19 expression was negatively associated with prognosis in OV, and further analysis revealed that KRT19 had promising diagnostic significance in distinguishing OV cancer from normal samples. GO-KEGG and GSEA analysis indicated that KRT19 was associated with multiple biological functions and pathways including epidermis development, apical junction, inflammatory response, and epithelial mesenchymal transition. By using different GEO series, we found that KRT19 was differentially expressed in OV-associated tissues. Furthermore, the increased KRT19 expression was positively correlated with the immune infiltration levels of the most immune cells in OV.Conclusion: This study demonstrated that KRT19 is a promising prognosis and diagnosis biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in OV, suggesting being a molecular target for immunotherapies.Keywords: KRT19, OV cancer, prognosis, biomarker, immune infiltration

Qiumei Lin,1,&ast; Zongwei Jiang,1,&ast; Dan Mo,2,&ast; Fengfei Liu,1 Yuling Qin,1 Yihua Liang,1 Yuchen Cheng,3 Hao Huang,1 Min Fang1,4 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Breast, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital, Nanning, 530025, People’s Republic of China; 3Department of Clinical Laboratory, Wuzhou Maternal and Child Health-Care Hospital, Wuzhou, People’s Republic of China; 4Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Huang; Min Fang, Email 1057226867@qq.com; fangmin@sr.gxmu.edu.cnBackground: Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients’ post-resection prognosis.Methods: We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α 1MG) and Beta2-microglobulin (β 2MG). Kaplan–Meier analysis assessed microglobulin’s impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade.Results: Patients with high β 2MG (≥ 2.395mg/L) had worse overall survival (OS). The nomogram integrated β 2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram’s discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility.Conclusion: Our β 2MG-based nomogram accurately predicts HCC patients’ post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.Keywords: hepatocellular carcinoma, nomogram, microglobulin, prognosis

Dongye He,1,2,&ast; Hailing Sun,1 Mei Zhang,1,3 Yanying Li,1,3 Fupeng Liu,1,2 Yanhong Zhang,1,3 Mingming He,1 Bo Ban1– 3,&ast; 1Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining, 272029, People’s Republic of China; 2Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, 272029, People’s Republic of China; 3Chinese Research Center for Behavior Medicine in Growth and Development, Jining, 272029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongye He; Bo Ban, Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining, 272029, People’s Republic of China, Tel/Fax +86 0537 2903579, Email hehe0917@mail.jnmc.edu.cn; banbo2011@163.comPurpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions.Patients and Methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated.Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429– 1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH.Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.Keywords: Kallmann syndrome, normosmic idiopathic hypogonadotropic hypogonadism, luteinizing hormone, follicle-stimulating hormone, genetic variant, hormone treatment

Fangfang Liu, Yinghan Dong, Yuan Yuan, Yingjie Jiang School of Psychology, Northeast Normal University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Yingjie Jiang, School of Psychology, Northeast Normal University, No. 5268, Renmin Street, Changchun, Jilin Province, People’s Republic of China, Email jiangyj993@nenu.edu.cnIntroduction: Interpersonal relationship serve as crucial of social support and a sense of security for left-behind children, playing a compensatory role in mitigating the absence of familial affection. Interpersonal distress can significantly impact their mental well-being. Although previous research has established a connection between empathy and interpersonal distress, the mechanisms by which empathy triggers interpersonal distress, as well as potential gender-based variations in this relationship, remain elusive. To bridge this gap in knowledge, this study investigates the mediating influence of emotion regulation and the moderating impact of gender in the relationship between empathy and interpersonal distress.Methods: A total of 713 rural left-behind children completed the Interpersonal Reactivity Index scale, Emotion Regulation Competence Scale, and Interpersonal Relationship Assessment Scale.Results: Pearson correlation analyses suggested strong significant correlations among empathy, emotion regulation ability, and interpersonal distress. Path analyses indicated that emotion regulation ability mediated the relationship between empathy and interpersonal distress. Furthermore, hierarchical regression analyses suggest a moderating effect of gender in the relationship between empathy and emotion regulation ability.Discussion: The present study reveals the role of emotion regulation ability and gender in the relationship between empathy and interpersonal distress, which has important theoretical and practical implications for the prevention and intervention of interpersonal distress in left-behind children. Moreover, it may strengthen the relationship between peer and teacher at school, and improve the quality of parent-child communication at home.Keywords: empathy, interpersonal distress, emotion regulation ability, gender, left-behind children

Canbin Dong,1,&ast; Fang Liu,1,&ast; Zuda Liao,2 Lanmei Lin,1 Runnan Wang,1 Juan Du,1 Wen Huang1 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, People’s Republic of China; 2Medical Insurance Office of Huashan Hospital Affiliated, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Wen Huang, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China, Tel +86-21-52889999, Fax +86-21-52887782, Email dujuan@huashan.org.cn; huangwen2@huashan.org.cnBackground: There are still some gaps in the summary and generalization of cosmetic-related adverse reaction reports.Objective: The aim of this study is to summarize and analyze the occurrence of cosmetic adverse reactions in Shanghai Han population by using available survey data.Materials and Methods: Collection, statistics and analysis of patients with cosmetic adverse reactions in Shanghai Huashan Hospital from 2017 to 2021.Results: Among the 1004 patients, most of them (96.71%) were diagnosed as cosmetic contact dermatitis, which often occurred within 3 days of using cosmetics (51.79%). A total of 260 patients were tested with patch test, but the compliance rate was only 18.08%. Among them, 240 patients underwent additional European standard allergen tests, and positive allergens were detected in 210 cases (87.5%). Univariate analysis revealed that dosage form (emulsion and cream), age (≤ 25 years) and the allergic ingredients triethanolamine, rose oil, propylene glycol, thiomersal and musk ambrette are associated with the occurrence of cosmetic adverse reactions within seven days. A logit prediction model was also successfully constructed: Logit (P) = 1.710– 0.796× 1 + 1.185× 2 − 3.650X3-1.335X4.Conclusion: This study complements the data reported on cosmetic adverse reactions in the Chinese Han population and suggests that in future clinical diagnosis and data collection, emphasis should be placed on patch testing, combining the patch test with cosmetic protoplast with the European standard allergen test to improve the detection rate.Keywords: adverse reaction reporting, cosmetics, contact dermatitis, personal care products, patch tests

Wei Deng,1,2 Yanhua Lu,1,2 Ping Hu,1,2 Qingqing Zhang,1,2 Shuangyan Li,1,2 Dong Yang,1,2 Ning Zhao,1,2 Kejian Qian,1,2 Fen Liu1,2 1Department of Critical Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Medical Innovation Center, First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Fen Liu, Email liufen9934@163.comBackground: Acute lung injury (ALI) is associated with a high mortality rate; however, the underlying molecular mechanisms are poorly understood. The purpose of this study was to investigate the expression profile and related networks of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in lung tissue exosomes obtained from sepsis-induced ALI.Methods: A mouse model of sepsis was established using the cecal ligation and puncture method. RNA sequencing was performed using lung tissue exosomes obtained from mice in the sham and CLP groups. Hematoxylin-eosin staining, Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and nanoparticle tracking analysis were performed to identify relevant phenotypes, and bioinformatic algorithms were used to evaluate competitive endogenous RNA (ceRNA) networks.Results: Thirty lncRNA-miRNA-mRNA interactions were identified, including two upregulated lncRNAs, 30 upregulated miRNAs, and two downregulated miRNAs. Based on the expression levels of differentially expressed mRNAs(DEmRNAs), differentially expressed LncRNAs(DELncRNAs), and differentially expressed miRNAs(DEmiRNAs), 30 ceRNA networks were constructed.Conclusion: Our study revealed, for the first time, the expression profiles of lncRNA, miRNA, and mRNA in exosomes isolated from the lungs of mice with sepsis-induced ALI, and the exosome co-expression network and ceRNA network related to ALI in sepsis.Keywords: sepsis, acute lung injury, inflammation, lung tissue exosomes, ceRNA networks

Guo-Li Du,1,2,&ast; Fen Liu,1,3,4,&ast; Hua Liu,1,2,&ast; Qi Meng,1,2 Ran Tang,1,2 Xiao-Mei Li,1,3 Yi-Ning Yang,1,5 Xiao-Ming Gao1,3,4 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 4Xinjiang Key Laboratory of Medical Animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 5People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-Ning Yang; Xiao-Ming Gao, Email yangyn5126@163.com; xiaominggao2017@163.comPurpose: We investigated the hypothesis that MHR (monocyte-to-high density lipoprotein cholesterol ratio) is related to the severity of coronary artery in ACS (acute coronary syndrome).Methods: In this case–control study, we recruited 15,853 participants undergoing the first time percutaneous coronary intervention (PCI) including 4093 normal controls, 10,518 chronic coronary artery disease (CAD), and 1242 ACS cases. Examination of demographic clinical data and biochemical profiles, as well as MHR values, were performed before PCI. The relationship between MHR and severity of coronary artery lesion in ACS was analyzed. We also used a flow cytometric assay to distinguish CD14+/CD16- classical monocyte subsets in peripheral blood mononucleated cells from CAD patients.Results: MHR was higher in patients with ACS compared with MHR in normal control and chronic CAD (normal control vs chronic CAD vs ACS: 0.46 ± 0.27 × 109/mmol vs 0.53 ± 0.29 × 109/mmol vs 0.73 ± 0.47 × 109/mmol, P < 0.001). MHR showed a significantly progressive increase as the angiographic severity of coronary lesions increased (single vessel lesion vs multi-vessel lesions in ACS: 0.54 ± 0.31 × 109/mmol vs 0.58 ± 0.35 × 109/mmol, P < 0.001), and classical monocyte subset to HDL-C ratio (CMHR) was increased in with CAD patients compared with control [4.69 (IQR, 1.06, 2.97) × 103/mmol vs 1.92 (IQR, 0.92, 3.04) × 103/mmol, P = 0.02]. Using a multivariate analysis, after adjusting for age, gender, body mass index (BMI), diabetes, and dyslipidemia, MHR was positively associated with multi-vessel lesions in ACS [OR (odds ratio): 1.28 (95% CI: 1.03– 1.59, P = 0.029)].Conclusion: MHR level could be a potential predictor of coronary artery lesion severity in ACS.Keywords: MHR, CAD, ACS, multi-vessel lesions, CMHR

Yanmei Song,&ast; Huiyuan Chu,&ast; Fang Liu, Wenjie Guo, Na Gao, Che Chen, Shisan Bao Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Che Chen; Shisan Bao, Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, 35, Dingxi East Road, Chengguan, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 187 09312856 ; +81 180 176 84959, Email chen72123@163.com; profbao@hotmail.comPurpose: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer.Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro.Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis.Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.Keywords: hepatocellular carcinoma, interleukin-36α, prognosis, biomarker

Jia Guo,1 Xuli Bao,1 Fuquan Liu,2 Jiang Guo,3 Yifan Wu,2 Fang Xiong,1 Jun Lu1 1Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Interventional Therapy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Interventional Therapy, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jun Lu, Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youan Men Wai, Fengtai District, Beijing, 10069, People’s Republic of China, Tel +86-010-83997153, Fax +86-010-83997000, Email lujun98@ccmu.edu.cnPurpose: Invariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure.Patients and methods: This open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE–iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety.Results: Fifty-four patients completed the study. Median PFS was significantly higher in TAE–iNKT patients (5.7 months [95% CI, 4.3– 7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3– 3.2 months]; hazard ratio 0.32 [95% CI, 0.16– 0.63]; P< 0.001). Higher ORR and DCR were observed in TAE–iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE–iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE–iNKT patients (9.2 months [95% CI, 6.0– 13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9– 3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95× 109/L, P = 0.007) and 12 (1.49 vs 0.89× 109/L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1– 2.Conclusion: iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.Keywords: hepatocellular carcinoma, invariant natural killer T cell, transarterial embolization, progression-free survival

Luying Qiu,1 Yaxuan Wang,2 Yuye Wang,1,3 Fang Liu,1 Shumin Deng,1 Weishuang Xue,1 Yanzhe Wang1 1Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Neurology, China-Japan Friendship Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yanzhe Wang, Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Affiliated Hospital of China Medical University, No. 155, Nanjing North Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of China, Tel +86-15040289417, Email yanzhewangcmu@126.comPurpose: The oxygen and glucose deprivation-reoxygenation (OGDR) model is widely used to evaluate ischemic stroke and cerebral ischemia-reperfusion (I/R) injury in vitro. Excessively activated microglia produce pro-inflammatory mediators such as matrix metalloproteinases [MMPs] and their specific inhibitors, tissue inhibitors of metalloproteinases [TIMPs], causing neuronal damage. Ursolic acid (UA) acts as a neuroprotective agent in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model keeping the MMP/TIMP balance with underlying mechanisms unclear. Our study used OGDR model to determine whether and how UA reduces neuronal damage by reversing MMP/TIMP imbalance caused by microglia in I/R injury in vitro.Methods: SH-SY5Y cells were first cultured with 95% N2 and 5% CO2 and then cultivated regularly for OGDR model. Cell viability was tested for a proper UA dose. We established a co-culture system with SH-SY5Y cells and microglia-conditioned medium (MCM) stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFNγ). MMP9 and TIMP1 levels were measured with ELISA assay to confirm the UA effect. We added recombinant MMP9 (rMMP9) and TIMP1 neutralizing antibody (anti-TIMP1) for reconfirmation. Transmission electron microscopy was used to observe cell morphology, and flow cytometry and Annexin V-FITC and PI labeling for apoptotic conditions. We further measured the calcium fluorescence intensity in SH-SY5Y cells.Results: The MCM significantly reduced cell viability of SH-SY5Y cells after OGDR (p

Xuehe Zhang,1,&ast; Jixin Zhang,1,&ast; Fen Liu,2 Wenling Li,1 Tong Zhang,1 Binbin Fang,2 Zhiyang Zhang,1 Qian Xie,1 Yining Yang,3 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: There is a lack of research on nutritional status and poor prognosis in patients with metabolic syndrome and heart failure. This study evaluated the relationship between nutritional status as defined by the PNI and adverse outcomes in patients with metabolic syndrome and heart failure.Methods: A total of 1048 heart failure patients with metabolic syndrome admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2019 were consecutively. PNI was used to assess their nutritional status.Results: A total of 51.0% of the patients were in the nonmalnutrition group (PNI≥ 45), 27.9% were in the mild malnutrition group (40≤PNI< 45), and 21.1% of patients were in the malnutrition group (PNI< 40). At 36 months of follow-up, after adjusting for other confounding factors, malnutrition (PNI< 40) was independently associated with all-cause death (HR: 1.787, 95% CI: 1.451– 2.201, P< 0.001) and cardiovascular death (HR: 1.837, 95% CI: 1.467– 2.301, P< 0.001). PNI showed additional prognostic predictive value when included in the established risk factor model, both for all-cause death (AUC: 0.620, 95% CI: 0.579– 0.661, P< 0.001) and cardiovascular death (AUC: 0.596, 95% CI: 0.555– 0.636, P< 0.001).Conclusion: In patients with metabolic syndrome and heart failure, malnutrition assessed by PNI is an independent predictor for all-cause death and cardiovascular death, and PNI is negatively correlated with the occurrence of adverse outcomes.Keywords: prognostic nutritional index, metabolic syndrome, heart failure, malnutrition, prognosis

Fang Liu,1 Fei Qi,2 Jingya Zhang,1 Yaqi Tan,1 Xiuying Zhang1 1Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fang Liu, Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-10-85231688, Fax +86-10-85231217, Email roseliufang@qq.comAbstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hostile cutaneous malignancy with dismal prognosis and unknown etiology with rarity. Most patients received traditional chemotherapy only has one year of median survival time. This article reports an 81-year-old male patient with BPDCN who presented with skin manifestations and was diagnosed with positive CD4, CD56, and CD123 immunohistochemical results. Systematic examination revealed lung involvement and cytopenia.Keywords: blastic plasmacytoid dendritic cell neoplasm, pathological feature, lung involvement, cytopenia, treatment, prognosis

Peixv Chen,1,2,&ast; Yiting Li,1,2,&ast; Di Wu,1,2 Fang Liu,1 Chao Cao1 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China; 2Medical College of Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Cao, Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, First Affiliated Hospital of Ningbo University, 59 Liuting Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Email caocdoctor@163.comBackground: Many studies have shown that active smoking leads to an increasing incidence of chronic obstructive pulmonary disease (COPD). However, studies interested in the effects of secondhand smoke exposure (SHS exposure) on COPD were less or underappreciated.Methods: A systematic review and meta-analysis was conducted to investigate the association between SHS exposure and the risk of COPD. Three databases (PubMed, Embase and Web of Science) were searched to obtain data. After assessing the study quality, stratified analyses were performed according to the region, gender, and duration of exposure. Cochran’s Q and I2 were utilized for heterogeneity assessment. To assess publication bias, we used a funnel plot and Egger’s test.Results: A total of 15 studies (6 cross-sectional studies, 6 case-control studies, and 3 cohort studies) with 25,592 participants were involved in this meta-analysis. This study showed that SHS exposure was associated with an increased risk of COPD (odds ratio (OR): 2.25, 95% CI: 1.40– 3.62, I2 = 98%, p < 0.01 for heterogeneity based on a random-effects analysis model), especially in those with a longer time exposure of more than 5 years was 4.38 (95% CI: 1.28– 15.00, I2 = 89%, p < 0.01 for heterogeneity based on a random-effects analysis model). In addition, SHS exposure also increases the risk of COPD in women (odds ratio (OR): 2.02, 95% CI: 1.52– 2.67, I2 = 0%, p = 0.89 for heterogeneity based on a random-effects analysis model).Conclusion: The findings suggest that SHS exposure is associated with the risk of COPD, especially for individuals with a long time exposed.Trial Registry: Prospero CRD42022329421.Keywords: COPD, secondhand smoke exposure, systemic review, meta-analysis

Nan Su,1,2 Lili Zhi,3 Fengxia Liu,4 Yongsheng Wang,5 Qingling Zhang,6 Xiansheng Liu,7 Xueyan Wang,8 Guodong Hao,9 Xiuqin Zhang,10 Qiang Hu,11 Monica Ligueros-Saylan,12 Alkaz Uddin,13 Jing Yang,14 Tiantian Liang,15 Liju Ding,16 Runqin Li,17 Chen Wang1,2,18– 21 1Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China- Japan Friendship Hospital, Beijing, People’s Republic of China; 2National Center of Respiratory Medicine, Beijing, People’s Republic of China; 3Department of Allergy, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, People’s Republic of China; 4Department of Allergy, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 8Allergy Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 9Department of Allergy, Tangshan Gongren Hospital, Tangshan, Hebei, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu, People’s Republic of China; 11Department of Pulmonary and Critical Care Medicine, Panzhihua Integrated Chinese and Western Medicine Hospital, Panzhihua, Sichuan, People’s Republic of China; 12Respiratory Clinical/Medical 2, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 13Analytics - Global Health DU, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 14Neuroscience & Respiratory Development Unit, Beijing Novartis Pharma. Co. Ltd, Beijing, People’s Republic of China; 15Respiratory Clinical Development, China Novartis Institutes for BioMedical Research Co., Ltd, Beijing, People’s Republic of China; 16GCTM-Group-2, China Novartis Institutes for BioMedical Research Co., Ltd, Shanghai, People’s Republic of China; 17New Products, Beijing Novartis Pharma. Co. Ltd, Shanghai, People’s Republic of China; 18National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 19Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 20Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 21Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Chen Wang, China- Japan Friendship Hospital, No. 2, East Yinghua Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 10-6510 5565, Fax +86 10-6510 5567, Email wangchen@pumc.edu.cnPurpose: Omalizumab was first approved in China in 2017 for the treatment of moderate to severe allergic asthma for adult and adolescent patients aged ≥ 12 years. In accordance with the Chinese Health Authority requirement, the post-authorization safety study (PASS) was conducted to evaluate the safety and effectiveness of omalizumab in a real-world setting in patients with moderate to severe allergic asthma in China over a 24-week observation period.Patients and Methods: This is a single-arm, non-interventional, multicenter, PASS conducted in adult, adolescent, and pediatric patients (≥ 6 years old) with moderate to severe allergic asthma receiving omalizumab in a real-world clinical setting from 2020 to 2021 in 59 sites of mainland China.Results: In total, 1546 patients were screened and 1528 were enrolled. They were stratified according to age (6 to < 12 years [n = 191]; ≥ 12 years [n = 1336]; unknown [n = 1]). Among the overall population, 23.6% and 4.5% of patients reported adverse events (AEs) and serious adverse events (SAEs), respectively. Among pediatric patients (6 to < 12 years), 14.1% and 1.6% patients reported AEs and SAEs, respectively. AEs that led to treatment discontinuation in both age groups were < 2%. No new safety signals were reported. Effectiveness results showed improvement in lung function, asthma control, and quality of life (QoL).Conclusion: The findings of the current study demonstrated that the safety profile of omalizumab was consistent with its known profile in allergic asthma, and no new safety signals were reported. Omalizumab treatment was effective in improving the lung function and QoL in patients with allergic asthma.Keywords: adverse drug events, allergic asthma, safety, effectiveness, omalizumab