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Yixin Chen,1,* Zhuo Yang,2,* Bin Nian,3 Chenglin Yu,4 Dilimulat Maimaiti,5 Min Chai,1 Xinran Yang,1 Xiuxian Zang,1 Dahai Xu1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 2Department of Emergency Intensive Care Unit of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 3Department of Ultrasonography, Yanbian University Hospital, Yanji, Jilin, People’s Republic of China; 4Department of Emergency Medicine, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 5Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahai Xu; Xiuxian Zang, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130000, People’s Republic of China, Tel +8615043032548 ; +8613596097922, Email xudahai0319@jlu.edu.cn; zangxx@jlu.edu.cnAbstract: Organophosphates (OPs) refers to a diverse group of phosphorus-containing organic compounds; they are widely used all over the world and have had an important beneficial impact on industrial and agricultural production and control of vector transmission. Exposure to OPs of different toxicities (high, moderate, slight, and low toxicity) can all have negative consequences on the nervous system, such as nausea, vomiting, muscle tremors, and convulsions. In severe cases, it can lead to respiratory failure or even death. Notably, OPs induce neuropathy in the nervous system through specific interactions with nicotinic or muscarinic receptors, phosphorylating acetylcholinesterase, or neuropathic target esterases. This review summarizes the possible toxicological mechanisms and their interplay underlying OP pesticide poisoning, including cholinesterase inhibition and non-cholinesterase mechanisms. It outlines the possible links between OP pesticide poisoning and neurological disorders, such as dementia, neurodevelopmental diseases, and Parkinson’s disease. Additionally, it explores OP interactions’ potential therapeutic implications that may help mitigate the deleterious impact of OPs on the nervous system.Keywords: organophosphate pesticides, neurotoxicity, acetylcholinesterase, neurodegenerative diseases

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318,People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songy_18@sumhs.edu.cnBackground: This study aims to evaluate the predictive value of bedside ultrasound evaluation of diaphragmatic dynamics in determining successful extubation outcomes for patients eligible for weaning.Methods: This prospective observational study was conducted on patients who were mechanically ventilated and ready for weaning during the spontaneous breathing trial (SBT). The diaphragm contraction and motion-related parameters of patients such as end inspiratory diaphragm thickness (DT-insp), end respiratory diaphragm thickness (DT-exp), diaphragm thickening fraction (DTF), diaphragmatic thickening fraction rapid shallow breathing index (DTF-RSBI), diaphragmatic excursion (DE), diaphragmatic excursion rapid shallow breathing index (DE-RSBI) were recorded and the association with failure in ventilatory extubation was analyzed. A receiver operating characteristic (ROC) curve was conducted to analyze the prediction of successful weaning.Results: Out of 95 patients, 14 (14.74%) died, and 68 (71.58%) were successfully extubated. There were significant differences between the two groups in all parameters except DT-exp. The results indicated that duration of mechanical ventilation (OR = 0.850, 95% CI: 0.770– 0.938, P = 0.001), DTF (OR = 1.214, 95% CI: 1.108– 1.330, P = 0.000), DTF-RSBI (OR = 0.917, 95% CI: 0.880– 0.954, P = 0.000), DE (OR = 127.02, 95% CI: 15.004– 1075.291, P = 0.000), DE-RSBI (OR = 0.752, 95% CI: 0.657– 0.861, P = 0.000) had predictive value for weaning. DTF and DE had a high sensitivity of 91.18%, 100%, respectively. Whereas, duration of mechanical ventilation, DTF-RSBI, DE-RSBI showed a high specificity of 81.48,85.19%, 81.48%. Considering all the above factors, the sensitivity was 88.24% and the specificity was 88.89%.Conclusion: Bedside ultrasound assessment of diaphragmatic parameters enables the detection of diaphragmatic dysfunction, thus proving valuable in predicting extubation success and facilitating a favorable weaning outcome.Keywords: diaphragmatic dynamics, bedside ultrasound, extubation, intensive care unit

Yihe Ma,1– 3,* Xiaojun Xiao,2,* Yutao Wang,3,* Jie Sun,4 Ping Tang,5 Jing Li,3 Xizhuo Sun,5 Damo Xu,1,2 Zifeng Yang,3 Shiguo Chen,4 Xiaoyu Liu2 1Department of Respiratory and Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Nanshan District Key Laboratory for Biopolymers and Safety Evaluation, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, People’s Republic of China; 5Department of General Practice, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyu Liu, State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China, Email lxy0901@szu.edu.cnPurpose: Synthesis and characterization of silver (Ag)/titanium dioxide (TiO2) nanocomposite (ATA) to investigate its antiviral activity against the H1N1 influenza virus and antiviral mechanisms.Materials and Methods: A water-dispersible ATA was prepared by a photocatalytic reduction process from AgNO3 and TiO2. The characterization of ATA was performed by ultraviolet-visible spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antiviral activities and the antiviral mechanism of ATA were investigated in detail by light microscopy, transmission electron microscopy and biological techniques such as cell cytotoxicity, 50% tissue culture infectious dose detection, western blot and reverse transcription-polymerase chain reaction.Results: These results showed the successful synthesis of ATA nanocomposite with uniform particle size and distribution. It demonstrated the highly efficient antiviral activity of ATA in a dose- and time-dependent manner, as indicated by the reduction of viral titer and the reduction of cytopathic effects caused by viral infection. In the presence of ATA, the structure of the H1N1 influenza virus is directly destroyed and even disintegrated, with the damaged surface membrane proteins and fuzzy contour. It reduces the infection efficiency of influenza by suppressing the activity and expression of hemagglutinin and neuraminidase. The results of mechanistic studies suggested that ATA nanocomposite primarily interferes with virus attachment to viral receptors on the cell surface.Conclusion: Our study suggests that ATA may be a good antiviral candidate against the influenza virus. Compared with AgNPs alone, our synthesized ATA nanocomposites can achieve similar viral inactivation rates using only a much smaller concentration of AgNPs, greatly reducing the amount of AgNPs and their potential side effects. It has great practical value for attaching ATA to the high-efficiency particulate air network in the air purifier, which can kill the virus attached to it and limit its spread.Keywords: silver, titanium dioxide, nanocomposites, antivirus, H1N1 influenza virus

Song Wen,1,&ast; Dongxiang Xu,1,&ast; Yue Yuan,1,&ast; Zhimin Xu,1 Yanyan Li,1 Min Gong,1 Xinlu Yuan,1 Ligang Zhou1,2 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally in this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +008613611927616, Email zhouligang1n1@163.comObjective: Serum tumor markers have been discovered to be elevated in individuals with diabetes mellitus (DM); however, their significance in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia (HHS) is unknown. We evaluated these indicators in the patients with DKA and HHS.Materials and Methods: We retrospectively collected the laboratory data of 565 diabetic patients from Shanghai Pudong Hospital between Jan, 2019 and May, 2023, including 300 patients with type 2 diabetes mellitus (T2DM), 206 with DKA, and 59 with HHS. Serum tumor biomarkers and further clinical laboratory tests were compared among the three groups. Patients with conspicuous tumor evidence were excluded from the study.Results: We found significantly higher levels of carbohydrate antigen 199 (CA199) in DKA (p< 0.01), carcinoembryonic antigen (CEA), complex prostate specific antigen (CPSA) (p< 0.01), prostate specific antigen (PSA) (p< 0.05) in HHS, as well as the plasma lipid profile, iron, and electrolytes, in addition to decreased thyroid function, hepatic and renal function, and cardiac function (p< 0.05). A Spearman correlational study revealed that osmolar levels were significantly positively correlated with myoglobin (MYO) and cardiac troponin I (cTNI), whereas serum iron concentration (r=0.520) was positively correlated with CEA levels in HHS. pH was negatively correlated with CA199 (r=− 0.195), while HbA1c (r=0.22), globin (r=0.341), and total cholesterol (TC) (r=0.191) were positively correlated with elevated CA199 levels. Moreover, the multilinear regression investigation identified osmolarity as a significant determinant for CEA, as well as other parameters, and all proved to be proper predictors for CEA in HHS via ROC curve establishment.Conclusion: Elevated CA199 levels in DKA were associated with acidosis, whereas HHS with elevated CEA levels may be related to iron homeostasis and could be predicted via the osmolar degree and other predictors.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, tumor markers, osmolar, iron homeostasis

Jianzhong Li,1,&ast; Yan Xiong,2,&ast; Mingyu Chen,1,&ast; Deyu Xu,1 Ling Zhou,1 Lei Shen,1 Guoyuan Lu1 1Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Department of Nephrology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Li; Guoyuan Lu, Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Email lijianzhong1511@suda.edu.cn; sdfyylgy@163.comPurpose: A major limitation of long-term peritoneal dialysis (PD) is peritoneal membrane dysfunction characterized by faster peritoneal solute-transport rate (PSTR). This study aimed to identify efficient complement factors in peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients that can predict the PSTR.Methods: A multiplex suspension protein array was used to screened related complement pathways in overnight peritoneal effluents among 58 CAPD patients. Then the related complement factors in lectin and classical pathways in effluents were analyzed using ELISA kits among another cohort of 129 CAPD patients. Logistic regression modeling was fitted to predict the PSTR of PD patients.Results: The multiplex suspension protein array showed complement factors including C2, C4b, C5, C5a, Factor D, Factor I, and MBL were detected in effluents of CAPD patients, and the effluent C2 Appearance rate (Ar) and C4b Ar levels were significantly correlated with D/P Cr and D/D0 glucose. The levels of effluents MASP-1 Ar, M-Ficolin Ar, C2 Ar and C4b Ar, which belong to the lectin pathway were also positively correlated with D/P Cr according the ELISA results and these parameters were expressed higher in the high and high-average (H/HA) groups according to the PET results. Moreover, effluent Masp-1 was independently associated with increased PSTR and adverse events related peritoneal transport function failure.Conclusion: This study suggested that the lectin pathway may be involved in local complement activation and peritoneal injury of PD patients, intraperitoneal level of Masp-1 was an independent predictor of increased PSTR in PD patients.Keywords: peritoneal dialysis, complement, lectin pathway, Masp-1, peritoneal solute-transport rate

Jianrong Zhang,1,&ast; Yiyu Tang,1 Shaoting Feng,1,&ast; Io Nam Wong,2,&ast; Yue Guo,1 Jun Zhang,1 Jiancong Chen,1 Daya Yang,1 Kunsong Zhang,1 Wenbao Yao,1 Rong Li,1 Yaying Bai,1 Shuqin Ding,1 Ming Kuang,1 Haipeng Xiao,1 Dan Xu1,3,&ast; 1Department of Medical Education, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2General Practice Research, Faculty of Medicine, Macau University of Science & Technology, Taipa, 999078, Macau; 3General Practice Research, Curtin School of Population Health/Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia&ast;These authors contributed equally to this workCorrespondence: Ming Kuang; Shuqin Ding, Email kuangm@mail.sysu.edu.cn; dingshq@mail.sysu.edu.cnIntroduction: The rising demand for knowledge updates and technological innovations in China has made clinical placement teaching challenging. Reforms for innovative teaching models through pilot classes have shown to improve students’ academic performance. This novel integration led to the announcement of healthcare collaboration in the Guangdong-Hong-Kong-Macao Greater Bay Area for projects within China’s “Global-Innovation-Hub” zones. First Affiliated Hospital (FAH) of Sun Yat-sen University (SYSU) in Guangzhou and the Faculty of Medicine (FMD) of Macau University of Science & Technology (MUST) in Macau have developed an inaugural project for FMD/MUST medical students to perform pre-internships at FAH-SYSU. This study aimed to reflect on students’ experiences with collaborative teaching and learning through medical curricular integration in the “Global-Innovation-Hub” zones designed by both institutions for developing integrated curriculum.Methods: FMD/MUST students attended medical clerkships at FAH-SYSU using a system-integrated curriculum in China’s “Global-Innovation-Hub” zones, allowing different education systems at different locations. Post-clerkship surveys ranked teaching models in conjunction with written reflections in response to post-clerkship questionnaires for all participating students. The teaching models were defined by the way supervisors’ interaction with students, and written reflections in response to the post-clerkship questionnaire were descriptively and semantically analysed.Results: The top-ranked teaching models include first “Student-led consultation under supervision in observers’ chair with discussion”, second “Observe consultation and discuss with the teacher in-between patients in observers’ chair” and third “Student-led consultation under supervision in consultants’ chair with discussion”. The post-clerkship questionnaires showed positive outcomes.Conclusion: This study demonstrates the successful delivery of collaborative teaching and learning through medical curricular integration in China’s “Global-Innovation-Hub” zones. This integration enables the development of a consistent and student-preferred teaching model being introduced into clinical placement curriculum. The unique location of China’s “Global-Innovation-Hub” zones in the Guangdong-Hong-Kong-Macao Greater Bay Area allows this integration to significantly improve students’ clinical reasoning learning.Keywords: Guangdong-Hong Kong-Macao Greater Bay Area, Global Innovation Hub, teaching model integration, clinical placement teaching, clinical reasoning learning

Min Chai,1,&ast; Patajiang Yusufu,2,&ast; Yixin Chen,1 Jiannan Chai,3 Xinran Yang,1 Yuqi Xiao,1 Hongwei Long,4 Dilimulat Maimaiti,2 Dahai Xu1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Laboratory, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Neurosurgery, Meihekou Central Hospital, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dahai Xu, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, People’s Republic of China, Tel +8615043032548, Email xudahai0319@jlu.edu.cn Dilimulat Maimaiti, Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, No. 1986, Qidaowan Road, Shuimogou District, Urumqi City, Xinjiang, People’s Republic of China, Tel +8617704972862, Email 3090760383@qq.comAbstract: Peptoniphilus asaccharolyticus is a gram-positive anaerobic coccus that can cause infections in immunocompromised individuals. P. asaccharolyticus causing empyema has not been reported earlier. Here, we present a novel case of empyema caused by P. asaccharolyticus. A 72-year-old male had a constant fever with difficulty breathing. A chest computed tomography scan revealed infiltration in the right lower lobe and pleural effusion. Following hospital admission, pleural fluid drainage was conducted, and the culture isolated P. asaccharolyticus. Initially treated with piperacillin/tazobactam, the patient experienced excessive thick sputum production, prompting a tracheostomy. Subsequent sputum cultures identified Acinetobacter baumannii. After transitioning to cefoperazone/sulbactam for antibiotic treatment and continued pleural effusion drainage, recovery was achieved. Empyema can be caused by P. asaccharolyticus and further complicated by a secondary infection with A. baumannii. Management should include appropriate antibiotic therapy, pleural drainage, vigilant monitoring, and supportive care. We aim to raise clinicians’ awareness of the potential for P. asaccharolyticus to cause empyema in immunocompromised patients and to provide early treatments, thereby improving morbidity and mortality.Keywords: Peptoniphilus asaccharolyticus, empyema, Acinetobacter baumannii, case report

Wenjuan Yi,1 Qionglin Bao,2 Dingkun Xu,3 Chenyu Long,1 Ruixin Fang,1 Wenlin Cheng,4 Jiquan Song,1 Huiting Feng1 1Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Wound Repair Center, Chronic Wound and Diabetic Foot Clinical Medical Research Center, Liyuan Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of China; 4Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Huiting Feng; Jiquan Song, Email feng_huiting@126.com; songjiq@126.comObjective: Diabetic foot ulcers (DFUs) are a serious complication of diabetes, characterized by impaired wound healing and high morbidity and mortality risks. While ETS1 is known to influence fibroblast pathological remodeling, its specific role in DFU and fibroblast wound healing remains unclear.Methods: Skin tissue samples from DFU patients were categorized by Wagner grades to analyze ETS1 expression. Primary fibroblasts derived from diabetes mellitus wound (DMFBs) were collected from wound margins to test migration ability and analyze cell phenotype by immunofluorescence; they were further treated with siETS1 and the ETS1 inhibitor YK-4-279. Techniques including Western blotting, quantitative Real-Time PCR (qRT-PCR), and immunofluorescence were used to assess the expressionof ETS1, Collagen I, and phenotype in DMFBs. Additionally, the binding sites between human ETS1 and the PP2A promoter were predicted by the UCSC and JASPAR databases. It intended to explore the negative transcriptional regulation of PP2A by ETS1 and its implications in fibroblast function and wound healing.Results: Fibroblasts derived from Wagner Grades II–IV exhibit differences in cell morphology, migratory ability, and phenotype. Our findings indicate a significant upregulation of ETS1 in Wagner III and IV. The downregulation of ETS1 was observed to enhance DMFB migration and increase the expression of Collagen I and α-SMA. These changes suggest a potential mechanism by which PP2A regulates the YAP/Hippo pathway in diabetic wound healing.Conclusion: ETS1 appears to impede the repair processes in DFUs, likely through the negative regulation of PP2A, affecting fibroblast function and wound healing.Keywords: diabetic wound, diabetic foot ulcer, ETS1, PP2A, YAP

Zhangxue Wang,1,2,&ast; Chunjuan Yang,3,&ast; Shushan Yan,4,&ast; Jiamei Sun,3,&ast; Jin Zhang,1,2 Zhuojian Qu,5 Wenchang Sun,3 Jie Zang,3 Donghua Xu1– 3 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Rheumatology and Immunology, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 3Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 4Department of Gastrointestinal and Anal Diseases Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 5School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghua Xu; Jie Zang, Email xudh@sdsmu.edu.cn; 18299094039@163.comAbstract: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) are the primary mechanism for the paracrine regulation of MSCs. They deliver proteins, nucleic acids, lipids, and other active compounds to various tissues and organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs and MSC-derived EVs (MSC-EVs) due to their immunomodulatory capabilities, according to mounting data. Since MSC-EVs have low immunogenicity, high stability, and similar biological effects as to MSCs themselves, they are advantageous over cell therapy for potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, systemic sclerosis, Sjogren’s syndrome, and other rheumatoid diseases. This review integrates recent advances in the characteristics, functions, and potential molecular mechanisms of MSC-EVs in rheumatic diseases and provides a new understanding of the pathogenesis of rheumatic diseases and MSC-EV-based treatment strategies.Keywords: mesenchymal stem cells, extracellular vesicles, exosome, immunomodulation, rheumatic disease

Qian Gui,1,&ast; Jingcai Meng,2,&ast; Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songye@tongji.edu.cnBackground: In recent years, diaphragm ultrasound (DUS) has been used to identify diaphragm dysfunction in the intensive care unit (ICU). However, there are few studies on DUS parameters to evaluate function, normal ranges, and influencing factors in population. The aim of this study is to provide a methodological reference for clinical evaluation of diaphragm function by measuring different DUS parameters in a healthy population.Methods: A descriptive study was conducted 212 (105 males, 107 females) subjects with normal spirometry underwent ultrasound imaging in this study. The diaphragm contraction and motion related parameters and shear wave velocity (SWV) were measured in the supine position. The effects of gender, age, body mass index (BMI) and lifestyle on diaphragm ultrasound parameters were analyzed.Results: The diaphragm thickness at end-expiration (DT-exp) was 0.14 ± 0.05 cm, the diaphragm thickness at end- inspiration (DT-insp) was 0.29± 0.10 cm, with thickening fraction (TF) was 1.11± 0.54. The diaphragm excursion (DE) was 1.68± 0.37cm and diaphragm velocity was 1.45± 0.41 cm/s during calm breathing. During deep breathing, the DE was 5.06± 1.40cm and diaphragm velocity was 3.20± 1.18 cm/s. The Diaphragm shear modulus—longitudinal view were Mean16.72± 4.07kPa, Max25.04± 5.58kPa, Min11.06± 3.88kPa, SD2.56± 0.98. The results of diaphragmatic measurement showed that the DT of males was significantly greater than that of females (P< 0.05), but there was no significant difference in TF. The DT-insp (r=0.155, P= 0.024) and the DT-exp (r=0.252, P=0.000) were positively correlated with age, and the DE during calm breathing was negatively correlated with age (r=− 0.218, P= 0.001) and BMI (r=− 00.280, P= 0.000). The DE (R=0.371, P=0.000) and velocity (R=0.368, P=0.000) during deep breathing were correlated with lifestyle.Conclusion: Our study provides normal reference values of the diaphragm and evaluates the influence of gender, age, body mass index and lifestyle on diaphragmatic morphology.Keywords: diaphragm, reference values, ultrasound, supine position

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

Yueyuan Wang,&ast; Bo Lv,&ast; Kai Fan, Cunjin Su, Delai Xu, Jie Pan Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Pan; Delai Xu, Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China, Email panzy1122@163.com; xdlsuzhou@163.comPurpose: Parkinson’s disease (PD) is a common neurodegenerative disease that severely affects patients’ daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.Methods: We divided 78 mice into six equal groups, including five model PD groups (W1–W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression.Results: We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages.Conclusion: Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.Keywords: Parkinson’s disease, metabolomics, biomarkers, metabolic disturbances, LC–MS

Hui Tang,1,&ast; Xiaoxia Ding,2,3,&ast; Youming Huang,2 Danfeng Xu,2 Yibin Fan1,2 1Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibin Fan, Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China, Tel +86 18806538451, Email fanyibin@hmc.edu.cnIntroduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation.Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content.Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes.Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.Keywords: vitiligo, fractional carbon dioxide laser, melanocytes, melanogenesis, vitiligo mouse models

Jiechenming Xiao,1 Dan Xu,1 Heng Yang,2 Huiping Mao1 1Department of Nursing, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China; 2Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of ChinaCorrespondence: Huiping Mao, Email tzmaohuiping@163.comBackground and Purpose: Ageing has become one of the major global public issues and active ageing has become a global goal. Accurate and reproducible assessment tools are a prerequisite for robust and reliable measurement of active ageing and policy formulation. However, a broad scoping review describing the characteristics and heterogeneity of assessment tools for active ageing is lacking. This study aims to comprehensively portray current active ageing assessment tools and their features.Methods: We conducted a scoping review, focusing on the Active Ageing Assessment Tool, and searched seven databases: CNKI, WanFang, PubMed, Embase, Web of Science Core Collection, Medline, and Proquest. The research process adhered to the methodological framework of Arkey and O’Malley and the PRISMA-ScR specification. More so, we registered the research program with the Open Science Framework.Results: Ultimately, we included twenty-two pieces of literature. The development of the active ageing assessment tool predominantly occurred between 2012 and 2023, with a focus on foreign countries (16 studies). All included literature presented multidimensional Active ageing assessment tools. Eighteen studies examined active ageing assessment tools at the macro level, while four studies focused on the individual level. Also, fourteen out of the twenty-two studies were based on the World Health Organization’s Theoretical Framework for Active Ageing. The literature contained only two active ageing assessment tools designed for specific subgroups of older people.Conclusion: Future development of active ageing assessment tools should integrate more comprehensive concepts and social theories of active ageing. Additionally, there is a need to explore active ageing measurement tools tailored for diverse subgroups of the older adults at various levels.Keywords: ageing, active ageing, healthy ageing, scope review

Dongru Du,1– 3,&ast; Bi Ran,1– 3,&ast; Dan Xu,1– 3 Lian Liu,1– 3 Xueru Hu,1– 3 Tingting Zeng,1– 3 Yongchun Shen,1– 3 Fengming Luo1– 4 1Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, 610200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongchun Shen; Fengming Luo, Tel +86 28 8542 2350, Fax +86 28 8558 2944, Email shen_yongchun@126.com; fengmingluo@outlook.comBackground: Sex steroid hormones, including testosterone and estradiol, play significant roles in various aspects of pulmonary health and diseases. However, although there were a few studies trying to link sex hormones with COPD, their effect remained limited due to small sample size and insufficient causal results. This study aims to investigate the association between sex hormones and chronic obstructive pulmonary disease (COPD) based on the National Health and Nutrition Examination Survey (NHANES) database and evaluate causality via a two-sample Mendelian randomization (MR).Methods: Data from NHANES 2013– 2016 were enrolled for the cross-sectional study. The association between sex hormones and COPD was evaluated via multivariable logistic regression. Sex-stratified analysis, subgroup analyses and interaction tests were performed to further evaluate the correlation. For MR analysis, data were collected from genome-wide association studies and FinnGen datasets. The inverse-variance-weighted (IVW) approach, along with four other approaches, was applied in the analysis. Further sensitivity analysis was conducted to assess the existence of pleiotropy and heterogeneity.Results: 7,617 eligible participants were enrolled in the cross-sectional analysis. Negative associations were observed in both testosterone-COPD (OR 0.770, 95% CI 0.626, 0.948, p = 0.018) and estradiol-COPD (OR 0.794, 95% CI 0.688, 0.915, p = 0.005) relationships after covariate adjustments. However, the results from IVW-MR analysis showed that no causal relationship was observed in either the testosterone-COPD (OR 0.83, 95% CI 0.53, 1.29, p = 0.407) or estradiol-COPD (OR 0.74, 95% CI 0.23, 2.38, p = 0.616) relationship, which was also supported by the other four approaches (all p values > 0.05).Conclusion: Although a significant negative association was observed between sex hormones and COPD, the results of MR analysis did not support the causality of this relationship. Our study suggested that sex hormones may indirectly rather than directly affect the development of COPD via potential covariates, which warranted further investigations.Keywords: sex steroid hormones, testosterone, estradiol, chronic obstructive pulmonary disease, NHANES, Mendelian randomization

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

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Jiangping Ye,1– 3 Dongxia Xu,1– 3 Rikang Yuan,1– 3 Shaoqing Cao,1– 3 Zhangyu Wang,1– 3 Yuqin Wang,1– 3 Chengsi Li,1– 3 Gangjun Zong1– 3 1Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu, People’s Republic of China; 2Anhui Medical University Fifth Clinical Medical College, Wuxi, Jiangsu, People’s Republic of China; 3Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Gangjun Zong, Email zonggj@163.comAim: The high morbidity and mortality associated with ST-segment elevation myocardial infarction (STEMI) are an urgent concern. This study aimed to investigate the ratio of lymphocyte count to C-reactive protein ratio (LCR) in multiple measurements in the perioperative period, exploring dynamic changes as the best predictor of major adverse cardiovascular events (MACE) in STEMI patients.Methods: We enrolled 205 STEMI patients, conducting blood counts at admission, 24 hours post-percutaneous coronary intervention (PCI), and at discharge. Cox proportional risk models evaluated factors independently associated with STEMI prognosis. The receiver operating characteristic (ROC) curve and the De-Long test determined the best predictor. Kaplan–Meier analysis assessed the prognostic value of LCR for STEMI patients. Statistical differences and correlations between LCR at 24 hours post-PCI and cardiovascular disease risk factors were also analyzed.Results: Gensini score (HR, 1.015; 95% CI, 1.007– 1.022; P < 0.001), total stent length (HR, 1.015; 95% CI, 1.002– 1.029; P=0.025), lipoprotein (a) (HR, 1.001; 95% CI, 1.000– 1.002; P=0.043), LCR at admission (HR, 0.995; 95% CI, 0.989– 1.000; P=0.002), and LCR at 24 hours post-PCI (HR, 0.587; 95% CI, 0.486– 0.708; P < 0.001) were independent risk factors for long-term STEMI prognosis after PCI. LCR at admission (cut-off value, 2.252; 95% CI, 0.040– 0.768; P < 0.001) and LCR at 24 hours post-PCI (cut-off value, 2.252; 95% CI, 0.831– 0.924; P < 0.001) effectively predicted MACEs occurrence, with the latter exhibiting a superior predictive effect (P< 0.001). Kaplan-Meier analysis revealed that patients with LCR at admission ≤ 50.29 and LCR at 24 hours post-PCI ≤ 2.25 had significantly higher risks of developing MACEs (Log-rank P < 0.0001).Conclusion: LCR at 24 hours post-PCI may be a superior marker for long-term MACE prediction in STEMI patients, serving as the best predictor for distant MACE occurrence.Keywords: lymphocyte, C-reactive protein, major cardiovascular adverse events, percutaneous coronary intervention, ST-segment elevation myocardial infarction

Xinran Yang,1,&ast; Chenglin Yu,2,&ast; Yixin Chen,1 Bin Nian,3 Min Chai,1 Dilimulat Maimaiti,4 Dahai Xu,1 Xiuxian Zang1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 2Department of Emergency Medicine, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 3Department of Ultrasonography, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dahai Xu; Xiuxian Zang, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130000, People’s Republic of China, Tel +86-15043032548 ; +86-13596097922, Email xudahai0319@jlu.edu.cn; zangxx@jlu.edu.cnAbstract: Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is characterized by symptoms such as fever, hemorrhage, and renal failure. However, the occurrence of acute pancreatitis (AP) in HFRS patients can be neglected, and high intraocular pressure (IOP) is exceedingly uncommon. In this report, we discuss the case of a 30-year-old male who presented with fever, nausea, vomiting, and abdominal pain. Physical examination revealed extremity petechiae rashes and elevated IOP. Laboratory tests indicated coagulopathy and renal failure. A computed tomography scan confirmed AP. Further testing revealed a positive anti-hantavirus IgM antibody. The patient received supportive care, fluid hydration, hemofiltration, mannitol, brinzolamide, and brimonidine to reduce IOP. Three days post-admission, the patient developed shortness of breath and chest pain. Subsequent chest computed tomography revealed pulmonary edema and bilateral pleural effusion. Treatment included oxygen supply, respiratory support, and thoracentesis, with continued hemofiltration. The patient recovered, regaining normal pulmonary and renal functions and normalized IOP. This case underscores the importance of comprehensive evaluations and vigilant monitoring in HFRS patients, particularly measuring IOP in those with visual complaints, to save lives and reduce morbidity.Keywords: hemorrhagic fever with renal syndrome, acute pancreatitis, high intraocular pressure, pulmonary edema

Shaoting Feng,1,&ast; Daya Yang,1,&ast; Kunsong Zhang,1,&ast; Denise Joy Findlay,2 Ming Kuang,1 Haipeng Xiao,2 Dan Xu1,2 1Department of Medical Education, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2General Practice Research, Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Australia&ast;These authors contributed equally to this workCorrespondence: Dan Xu; Ming Kuang, Email daniel.xu@curtin.edu.au; kuangm@mail.sysu.edu.cnPurpose: Australian general practice training uses external clinical teaching (ECT) visits for formative work-based assessments. ECT visits appoint senior general-practitioners (GPs) observe trainee GPs’ consultations, provide feedback, and make performance-enhancing recommendations. As ECT visits are one of the best assessment tools in Australian GP training, there is limited evidence of its use in undergraduate teaching. This study aims to introduce ECT visits and evaluate assessment tools during senior medical students’ GP placement.Methods: This study included external and internal GP supervisors and twenty-five Chinese and Australian students during GP placements. The supervisors provided structured in-person feedback, while the ECT assessment tool used a standardised, validated feedback platform to assess every component of a consultation. Students’ feedback was recorded and collected by both internal and external supervisors, and then semantically analysed by external supervisors.Results: Twenty-five ECT visit feedbacks were collected and analysed semantically. All participating students rated ECT visits excellently and confirmed the relevance of assessment tools for discussions with supervisors to achieve the designed learning outcomes. Chinese students rated the assessment tools as innovative from a cultural perspective and recommended the ECT visit teaching model and assessment tools to their home university, whereas Australian students suggested more ECT visits during GP placements. Time management was a limitation for both the students and supervisors.Conclusion: ECT visit is an innovative placement teaching model and work-based assessment tool for senior medical students’ GP placements, and is rated as the most preferred formative assessment tool. The limitations of this study include small group of students/supervisors and lack of patient feedback; however, all of these limitations can be overcome by involving multiple GP clinics in ongoing large-scale study. ECT visits can be introduced quantitatively into students’ GP placement curricula to improve clinical reasoning, learning, and quality assurance with assessments during clinical placements.Keywords: external clinical teaching, general practice placement, senior medical students placement learning, clinical reasoning learning, work-based assessment

Jiapei Yao,1,2 Xindie Zhou,1,3 Dongmei Xu,1 Ting Liu,1 Yuanyuan Gui,4 Yong Huang1,3 1Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Hunan Normal University, Changsha, People’s Republic of China; 3Changzhou Medical Center, Nanjing Medical University, Changzhou, People’s Republic of China; 4Department of Psychogeriatric Intensive Care Medicine, Xianlin Campus, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of ChinaCorrespondence: Yuanyuan Gui; Yong Huang, Email Guiyuanyuansltd@163.com; huangyong@njmu.edu.cnObjective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it.Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis.Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance.Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.Keywords: secondary traumatic stress, emergency and intensive care department nurses, anxiety, depression, emotional intelligence

Ling Tong,1,2,&ast; Yuan Wang,1,2,&ast; Dewu Xu,3 Yibo Wu,1 Ling Chen2 1Human Reproductive and Genetic Center, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 2Department of Breast Surgery, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Department of Medicine Education, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Chen, Department of Breast Surgery, Affiliated Hospital of Jiangnan University, Wuxi, 214062, People’s Republic of China, Email Rainbow_lyn@163.com Yibo Wu, Human Reproductive and Genetic Center, Affiliated Hospital of Jiangnan University, Wuxi, 214062, People’s Republic of China, Email moliaty@aliyun.comObjective: The fear of cancer recurrence (FCR) is a generalized psychological problem among cancer patients and their spouses. The purpose of this study is to investigate the current status of cancer recurrence fear among breast cancer patients and their spouses, as well as its predictive factors.Methods: A total of 155 breast cancer patients and their partners between March 2022 to Feb 2023 were selected from Affiliated Hospital of Jiangnan University. The survey was investigated by fear of progression questionnaire-short form (FoP‑Q‑SF), fear of progression questionnaire‐short form for partners (FoP‐Q‐SF/P), family resilience questionnaire (FaRE), and health literacy management scale (HeLMS). Predictors were assessed using univariate and multivariable regression analyses.Results: 52.9% (n=82) of breast cancer patients and 51.6% (n=80) of their spouses experienced high levels of fear of cancer recurrence (FCR). There was a positive correlation between the FCR of the patients and their spouses, while family resilience and health literacy were statistically significant negative predictive factors for breast cancer patients’ fear of cancer recurrence.Conclusion: In summary, the study found that the partner’s FCR, health literacy and family resilience were closely related to the FCR in breast cancer patients. Therefore, healthcare workers can reduce the patient’s FCR by reducing the FCR in spouses, improving patients’ health literacy and family resilience in the future. In practical application, these findings hold significant implications for developing comprehensive care plans and interventions targeting FCR in breast cancer patients. By focusing on patients’ partners and providing appropriate support and resources, healthcare professionals can promote patients’ psychological well-being and overall health, leading to improved quality of life.Keywords: breast cancer, family factors, fear recurrence, health literacy

Zheng Xiang,&ast; Yueyuan Wang,&ast; Yuchen Qu, Bo Lv, Junping Han, Delai Xu, Kai Fan, Cunjin Su, Zhu Shen Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cunjin Su; Zhu Shen, Email sucjgh@vip.163.com; jsdxsz@163.comObjective: To assess the key factors influencing the effectiveness of nirmatrelvir/ritonavir in treating elderly patients with COVID-19.Methods: This study was conducted on patients aged ≥ 60 who were admitted to the Second Affiliated Hospital of Soochow University for COVID-19 infection and were treated with nirmatrelvir/ritonavir. Clinical information was collected from patients and steady-state blood concentrations of nirmatrelvir and ritonavir were measured. Factors associated with treatment effects were searched by univariate and multivariate analysis.Results: A total of 68 (51 males and 17 females) patients had a median age of 80 (73.0– 84.8) years were enrolled in this study. The blood concentration measurements (trough concentrations) of nirmatrelvir and ritonavir were 5.1 (2.6– 7.1) and 0.4 (0.2– 0.9) μg/mL, respectively. Adverse drug reaction was reported in 4 (5.9%) patients. Univariate analysis showed that age, clinical classification, APACHE II score, total bilirubin (TBil), aspartate transaminase (AST), lactate dehydrogenase (LDH), and total cholesterol (TC) were significantly associated with the effectiveness of treatment (P value < 0.05). Concentration of nirmatrelvir was also associated with treatment outcome (P value < 0.1). Based on the results of univariate analysis, the above factors were introduced into the multiple linear regression equation as independent variables, and the results showed that clinical classification was included in the regression equation model and was the most important factor affecting the treatment outcome. By receiver operating characteristic curve analysis, the area under curve of age + biochemical indicators + APACHE II score + clinical classification was 0.968 (95% CI = 0.919– 1.000; P < 0.0001). Among the 68 patients included in the study, 4 cases experienced adverse drug reactions.Conclusion: Age, clinical classification, APACHE II score, TBil, AST, LDH, and TC were significantly associated with the effectiveness of treatment in elderly patients with COVID-19.Keywords: nirmatrelvir/ritonavir, COVID-19, elderly patients, effectiveness

Huangqi Duan,&ast; Yu Shen,&ast; Chen Wang, Weimin Xia, Shun Zhang, Shenggen Yu, Ding Xu, Qifeng Cao, Hailong Liu, Haibo Shen Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hailong Liu; Haibo Shen, Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email liuhailong@xinhuamed.com.cn; shenhaibo@xinhuamed.com.cnBackground: Cuproptosis-related gene and long non-coding RNA (lncRNA) modulation of cancer regulation is well-established. This investigation aimed to elucidate the prognostic implications of cuproptosis-associated lncRNAs in muscle-invasive bladder cancer (MIBC).Methods: Employing the Cancer Genome Atlas (TCGA) and IMvigor210 cohorts, bioinformatics and statistical analyses probed the prognostic relevance of cuproptosis-related lncRNAs.Results: Co-expression analysis revealed tight associations between lncRNA expression and cuproptosis-linked genes, with 13 cuproptosis-related lncRNAs found to correlate with MIBC prognosis. Lasso regression identified a six-lncRNA prognostic signature, enabling patient stratification into high- and low-risk categories. Tissue validation substantiated differential expression of FAM13A-AS1, GHRLOS, LINC00456, OPA1-AS1, RAP2C-AS1, and UBE2Q1-AS1 between MIBC tumor and normal tissues. Comparative analyses of tumor microenvironments and immune profiles between risk groups disclosed elevated immunosuppressive molecule expression, including programmed cell death-1 (PD-L1) and T-cell immunoglobulin-3 (TIM-3), in high-risk individuals.Conclusion: These findings suggest that cuproptosis-related lncRNAs may modulate the expression of immunosuppressive molecules, thereby influencing MIBC tumorigenesis and progression. Further exploration is warranted to unveil novel therapeutic targets for MIBC based on the expression patterns of cuproptosis-related lncRNAs and their impact on immune responses in the tumor microenvironment.Keywords: cuproptosis-related lncRNAs, immunosuppressive molecules, MIBC, prognostic, risk scores

Weinan Hu,&ast; Wenting Cai,&ast; Yan Wu, Chengda Ren, Donghui Yu, Tingting Li, Tianyi Shen, Ding Xu, Jing Yu Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ding Xu; Jing Yu, Email 15821885240@163.com; dryujing@aliyun.comBackground: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.Methods: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.Results: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.Conclusion: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD. Keywords: age-related macular degeneration, choroidal neovascularization, cell-penetrating peptide, ranibizumab, conbercept, drug delivery

Tessa Fischer,1,2 Jenna Tucker,1,2 Charlie Li,3 Kyungmi Min,3 Dadong Xu,3 Laurence R Upjohn,1 Madhur Kumar1 1Food and Drug Branch, California Department of Public Health, Sacramento, CA, USA; 2California Epidemiologic Investigation Service (Cal EIS) Fellowship Program, California Department of Public Health, Sacramento, CA, USA; 3Food and Drug Laboratory Branch, California Department of Public Health, Richmond, CA, USACorrespondence: Madhur Kumar, Food and Drug Branch, California Department of Public Health, 1500 Capitol Avenue, MS 7602, Sacramento, CA, 95814, USA, Email madhur.kumar@cdph.ca.govPurpose: The Food and Drug Administration (FDA) has warned against tainted products for sexual enhancement containing prescription phosphodiesterase-5 (PDE5) inhibitors marketed as dietary supplements. The California Department of Public Health (CDPH)’s Food and Drug Branch (FDB) initiated a study to assess the presence of such adulterated products, specifically to identify the presence of PDE5 inhibitors in dietary supplements marketed for sexual enhancement, sampled at local retail locations.Methods: A convenience sample of products marketed as sexual enhancement dietary supplements was purchased from retail stores, within a 15-mile radius of downtown Sacramento, California. Samples were submitted to the Food and Drug Laboratory Branch (FDLB) and screened for 19 different PDE5 inhibitors using liquid chromatography-mass spectrometry. Samples were collected and analyzed from 2016 to 2018.Results: One hundred and two different products were purchased from 28 different retail locations. Sixty-seven percent were found to be adulterated with at least one PDE5 inhibitor. Of the positive samples, 40% were found to contain one PDE5 inhibitor and 60% were found to contain two or more. Sildenafil was the most common PDE5 inhibitor identified (74%), followed by tadalafil (59%). Eighteen percent of the tested samples had been associated with previous FDA warnings listed in their Tainted Products Database. Of these warning-associated samples, 72% were found to contain PDE5 inhibitors and 46% of these contained at least one of the same adulterants reported by the FDA.Conclusion: FDA reports and warnings have focused on dietary supplements found online or through screenings of international mail shipments. FDB results add to FDA findings by demonstrating that such adulterated products marketed for sexual enhancement are also sold at retail locations in California. These products have the potential to cause severe adverse health effects and therefore, it is essential to raise awareness of this significant public health concern.Keywords: dietary supplements, sexual enhancement products, adulteration

Min Jiang,1,&ast; NanNan Pang,2,&ast; Jing Wang,1 Zheng Li,1 Dan Xu,1 Jing Jing,1 Dan Chen,3 Fengsen Li,1 Jianbing Ding,4 Qifeng Li5 1Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, 830017, Xinjiang, People’s Republic of China; 4Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830011, Xinjiang, People’s Republic of China; 5Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qifeng Li, Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830054, People’s Republic of China, Tel +86-991 3056239, Fax +86-991 3056237, Email liqiqi521@sina.comBackground: Studying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.Methods: This study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(M&phis;), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.Results: COPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.Conclusion: Tuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.Keywords: chronic obstructive pulmonary disease, COPD, autoantibody, autoimmunity, inflammatory phenotype

Zhuangzhuang Jiang, Dongjuan Xu, Hongfei Li, Xiaolan Wu Department of Neurology, Dongyang People’s Hospital, Affiliated to Wenzhou Medical University, Dongyang, Zhejiang, People’s Republic of ChinaCorrespondence: Dongjuan Xu, Tel +86 13588620108, Email xdj0108@126.comObjective: This study aimed to create and validate a novel nomogram to predict the risk of symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT).Methods: In this retrospective study, 784 patients with AIS who received IVT were enrolled. The patients were randomly divided into two groups: a training set (n=550, 70%) and a testing set (n=234, 30%). Utilizing multivariable logistic regression analysis, relevant factors for the predictive nomogram were selected. The performance of the nomogram was evaluated using various metrics, including the area under the receiver operating characteristic curve (AUC-ROC), the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA).Results: Multivariable logistic regression analysis showed that specific factors, including National Institutes of Health Stroke Scale (NIHSS) scores, Early infarct signs (EIS), and serum sodium, were identified as independent predictors of sICH. Subsequently, a nomogram was constructed using these predictors. The AUC-ROC values of the nomogram were 0.864 (95% CI: 0.810– 0.919) and 0.831 (95% CI: 0.770– 0.891) in the training and the validation sets, respectively. Both the calibration plots and the Hosmer-Lemeshow goodness-of-fit test showed favorable agreement in both the training and the validation sets. Additionally, the DCA indicated the practical clinical utility of the nomogram.Conclusion: The novel nomogram, which included NIHSS, EIS and serum sodium as variables, had the potential for predicting the risk of sICH in patients with AIS after IVT.Keywords: ischemic stroke, symptomatic intracranial hemorrhage, thrombolysis, nomogram

Dan Xu,1,2 Shaoting Feng,1 Daya Yang,1 Shuqin Ding,1 Johan B Rosman,2 Ming Kuang,1 Haipeng Xiao1 1First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, AustraliaCorrespondence: Dan Xu; Haipeng Xiao, Email daniel.xu@curtin.edu.au; xiaohp@mail.sysu.edu.cnPurpose: Clinical placement teaching could be challenging due to time constraints, lack of effective teaching models and consensus approaches. Learner-centred approach facilitated deeper learning by demonstrating “seeing-patients-under-supervision” being ideal during Residential-Aged-Care-Facility (RACF)-visit in GP clinical placements. The study aimed to reflect on the students’ experiences in aged-care visits by applying an innovative teaching model of “students-being-the-GP-clinician-in-charge-of-RACF-visit-ward-round-under-the-supervision-of-clinical-supervisor”. Through students’ reflections, this study identified 12 commonly managed RACF problems to be introduced into the curriculum to optimise clinical reasoning learning during RACF-visit.Methods: This qualitative study used online surveys and interviews. All participating students reported all the encountered cases during the RACF visit through an online survey. The participating students acted as GP in charge of all clinical interactions with patients, caregivers, and nurses during RACF visits and final management plan discussions with GP supervisors to ensure clinical-service safety and teaching-and-learning quality. The interview questionnaires applied standard-and-open-ended-questions to examine the impact of this innovative teaching model on clinical-reasoning-learning, clinical-competence-improvement, Objective Structured Clinical Exam (OSCE) preparation, limitations-from-students’-patients’-and-supervisors’ perspectives, and intern readiness.Results: An online survey summarising students’ encountered cases was returned by 30 students. The 12 most commonly-managed problems were tabulated. Falls, urinary tract infections, and behavioural and psychological symptoms of dementia were the three most commonly-managed problems. All thirty students’ reflections indicated the positive impact of the innovative-teaching-models on “Improving-Clinical-Reasoning-Learning”, “Enhancing-Clinical-Competency”, “Enriching-Salient-Learning-Points”, “Facilitating-Feedback-Discussion-with-Supervisor”, “Strengthening-OSCE-exam-preparation”, “Understanding-the-Limitation-from-students’-patients’-and-supervisors’-perspectives”, “Enabling-intern-readiness”. Twelve students’ individual reflections were demonstrated.Conclusion: This qualitative pilot study demonstrated through students’ reflection that “Student-doctor-in-charge-of-nursing-home-round” is an innovative teaching model for clinical reasoning learning. This model extended the concepts of “cognitive-apprenticeship” in the context of modern medical education. Students’ reflections and summary of commonly managed problems indicated the need for further study to verify the feasibility of implementing this teaching model in the formal curriculum and creating a RACF-visit-specific curriculum for students.Keywords: clinical reasoning learning, learner-centred approach, cognitive apprenticeship

Tingting Hu,1,&ast; Nannan Pang,2,&ast; Zheng Li,1 Dan Xu,1 Jing Jing,1 Fengsen Li,1 Jianbing Ding,3 Jing Wang,1 Min Jiang1 1Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang; Min Jiang, Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999908413 ; +86-13999162873, Email jingw_xj@163.com; 250579087@qq.comBackground: Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD.Methods: The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques.Results: We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control.Conclusion: m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.Keywords: chronic obstructive pulmonary disease, COPD, N6-methyladenosine, m6A, M1 macrophages, mitogen-activated protein kinase signaling pathway, MAPK signaling pathway

Xueping Yang,1,2,&ast; Changhong Guo,3,&ast; Guangjie Wu,1,&ast; Kai Zhao,4 Dong Xiang,1 Dong Xu,5 Dong Liu,1 Yan He1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pharmacy, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, People’s Republic of China; 3Department of Scientific Education, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, 434000, People’s Republic of China; 4Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 5Department of Infection Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan He; Dong Liu, Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email heyan_may@hotmail.com; ld2069@outlook.comPurpose: Due to the spread of antimicrobial-resistant bacteria and poor penetration of many antimicrobial drugs across the blood–brain barrier following intravenous administration, treatment of central nervous system (CNS) infections is challenging, especially infections caused by carbapenem-resistant organisms (CRO). Intraventricular (IVT) infusion of antimicrobial drugs could be a choice. This report aims to describe a patient with CNS infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB) which was successfully treated with IVT combined with intravenous (IV) colistin sulfate.Methods: A case of CNS infection caused by CRAB after a craniocerebral injury was presented. The patient was treated with IVT together with IV colistin sulfate. Moreover, literature on the regimens and safety of colistin sulfate were also reviewed and summarized.Results: Intraventricular (50,000 U, qd/100,000 U, qd) combined with IV (500,000 U, q12h/500,000 U, q8h) colistin sulfate was given to the patient, and the CNS infection was successfully controlled. The patient was finally transferred back to a local hospital for rehabilitation treatment. No nephrotoxicity or neurotoxicity was observed during the therapy.Conclusion: IV combined with IVT colistin sulfate is effective in the treatment of CNS infections caused by CRAB. IVT concomitant IV colistin sulfate might be a therapeutic option worth considering in the treatment of CNS infections caused by CRO.Keywords: central nervous system infection, Acinetobacter baumannii, intraventricular administration, colistin sulfate, colistin, polymyxin

Runqi Cheng,1 Tiansheng Wang,1 Yuankun Cai,1 Songshan Chai,1 Lei Shen,1 Dongyuan Xu,1 Jingyi Yang,1 Chuqiao Yue,1 Jianzhang Pu,2 Nanxiang Xiong1 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Department of Neurosurgery, Beijing Shunyi District Hospital, Shunyi Teaching Hospital of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Nanxiang Xiong, Email mozhuoxiong@163.comObjective: To predict the volume and shape of the balloon before PBC by reconstructing the Meckel’s cave (MC) and establishing a volumetric measurement model, supporting preoperative preparation and intraoperative decisions.Methods: The clinical data of 31 patients with good therapeutic effects who underwent PBC are retrospectively collected, including preoperative MRI, the volume of contrast agent injected into the balloon, and intraoperative lateral X-ray images. The MC on the affected side of the 31 patients is reconstructed based on MRI using 3D Slicer, while the volume of the MC is calculated to compare with the volume of contrast agent. The width (W) and length (L) of the model of the MC in lateral view are measured and used to classify the shape of the MC based on W/L. The consistency between the W/L of the model of the MC and the W/L of the intraoperative balloon is evaluated.Results: For volume, the mean value of the models of the MC (V1) in 31 patients is 399.77± 155.13 mm³, while the mean value of the contrast agent injected during PBC (V2) is 539.03± 111.93 mm³. The formula obtained by linear regression is V2= 392.1 + 0.3676×V1. Based on the value of W/L, the shape of the MC is classified into thin “pear” in 5 patients (16.13%), standard “pear” in 22 patients (70.97%), and square “pear” in 4 patients (12.90%). There is no significant difference in W/L between the models of the MC and the intraoperative balloons in 31 patients (P=0.221).Conclusion: In 31 patients with good efficacy, it is verified that the prediction of the MC before PBC by 3D Slicer is consistent with the actual situation of the intraoperative balloon. This method can provide certain basis for preoperative preparation and intraoperative judgment.Keywords: trigeminal neuralgia, percutaneous balloon compression, Meckel’s cave, 3D Slicer, reconstruction

Li Gu,1 Tao Ai,2 Ling Pang,1 Dong Xu,1 Han Wang3 1Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 3Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Dong Xu, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, People’s Republic of China, Email 89650793@qq.com Han Wang, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, People’s Republic of China, Email hanwang@tjh.tjmu.edu.cnAbstract: Voriconazole is the therapy of choice for aspergillosis. However, hepatotoxicity is the most common reason for the discontinuation of voriconazole. In contrast, posaconazole is well tolerated, with a low incidence of hepatotoxicity. In most cases, hepatotoxicity is associated with high voriconazole trough concentration influenced mainly by cytochrome P450 (CYP) 2C19 gene polymorphism. Compared with normal metabolizers, intermediate and poor metabolizers generally have higher voriconazole trough concentrations with an increased risk of hepatotoxicity. Here, we describe changes in hepatotoxicity throughout azole therapy in a patient with pulmonary aspergillosis (PA). Nevertheless, the patient with the normal metabolism genotype of CYP2C19 developed severe hepatotoxicity caused by voriconazole but tolerated posaconazole well, with a lack of direct cross-hepatotoxicity between the both. Interestingly, the patient had a high risk of hepatotoxicity at a low voriconazole trough concentration. Fortunately, elevated liver enzymes declined to the baselines with posaconazole treatment.Keywords: hepatotoxicity, drug-induced liver injury, drug trough concentrations, voriconazole, posaconazole, pulmonary aspergillosis

Yan Teng,1,&ast; Hui Tang,2,&ast; Yong Yu,1 Yibin Fan,1 Xiaohua Tao,1 Danfeng Xu1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danfeng Xu; Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Gongshu District, Hangzhou, 310014, People’s Republic of China, Tel +86-13567122384 ; +86-13505811700, Email 3100102508@zju.edu.cn; taoxiaohua@hmc.edu.cnBackground: There is limited literature on AD with a predominant involvement of nipple among the adult male group. SARS-CoV-2 infection might have been an exacerbating factor of AD by initiating the “cytokine storm”. Conventional treatment suffers from a dilemma of poor efficacy and a high recurrence. The JAK inhibitors have been clinically applied to treat the AD with a good outcome.Patients and Methods: We present a case of a 28-year-old male AD patient with a predominant nipple involvement successfully treated with JAK inhibitor abrocitinib, with no adverse affects.Results: The case shows a good clinical efficacy of JAK inhibitor abrocitinib in the treatment of AD with a predominant nipple involvement during the COVID-19 pandemic with a rapid and long-term symptomatic relief.Conclusion: JAK inhibitor abrocitinib might become a promising agent for the treatment with AD with a predominant uncommon region like nipple that might be resistant to conventional therapies during the COVID-19 pandemic.Keywords: atopic dermatitis, nipple and areola, JAK inhibitors, abrocitinib, COVID-19

Yujie Peng,1 Xiaochuan Wu,1 Xinyu Ma,2 Dingli Xu,3 Yang Wang,4 Dongdong Xia1 1Orthopeadic Department, The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Emergency Department, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, People’s Republic of China; 3Clinical Department, Health Science Center, Ningbo University Zhejiang, Ningbo, People’s Republic of China; 4Orthopeadic Department, Ningbo No.6 Hospital, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Dongdong Xia, Email gukeyisheng0525@163.comBackground: Sarcopenia and osteoporosis vertebral compression fractures (OVCF) are common diseases that increase with age. This study aimed to investigate the effects of sarcopenia on OVCF patients after percutaneous kyphoplasty (PKP).Methods: Data of 101 patients who were treated with single-level PKP between January 2021 and March 2022 at Ningbo No.6 Hospital were enrolled. Forty-five OVCF patients with sarcopenia who met our inclusion criteria were included in the Sarcopenia-PKP group (SPKP group), and 56 patients in the Normal-PKP group (NPKP group). All clinical and radiological data were collected from medical records. Baseline characteristics, operation-related parameters (operation time, time to ambulation, hospital stay, surgery segment), clinical outcomes (visual analog score [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association Scores [JOA] of lumber), radiological outcomes (vertebral anterior height rate and local kyphosis angle), Macnab score, and complications were evaluated and compared.Results: There were no significant differences in age, sex, surgical segment preoperative VAS score, ODI, or JOA between the two groups (P > 0.05). The SPKP group had a significantly lower body mass index (BMI), bone mineral density (BMD), and smooth muscle index (SMI) than the NPKP group (P < 0.05). Significantly longer hospital stays and time to ambulation in SPKP group than NPKP group (3.7± 0.8 vs 3.4± 0.5 and 2.0± 0.8 vs 1.6± 0.5, P < 0.05). In SPKP group, significantly better clinical outcomes at 6- and 12-months follow-up were observed in NPKP group than SPKP group (P < 0.05), and NPKP group showed significantly better in vertebral anterior height rates than SPKP group after 6-month follow-up (P < 0.05). Moreover, there were significantly more cases of complications in the SPKP group (P < 0.05).Conclusion: Sarcopenia could reduce the clinical effect of percutaneous kyphoplasty, and furthermore. Related studies are needed to verify the effect of sarcopenia on OVCF patients.Keywords: sarcopenia, percutaneous kyphoplasty, osteoporosis vertebral compression fracture, clinical effect

Wenbing Zhang,1 Jian Ding,2 Wenhai Wang,1 Duo Wang,3 Yinping Pan,4 Dexin Xu5 1Department of Cardiology, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of China; 2Department of Electrodiagnosis, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of China; 3Department of Geriatrics, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of China; 4Department of Pediatrics, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of China; 5Department of Orthopedics, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of ChinaCorrespondence: Dexin Xu, Department of Orthopedics, Jilin Province FAW General Hospital, Changchun, 130000, People’s Republic of China, Email bonewax@sina.comAbstract: Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted and specified according to the subtype of amyloidosis and the presence of complications. However, there are still significant challenges in treating this condition due to its complexity and lack of effective treatments. The prognosis for patients with cardiac amyloidosis is poor. Despite recent advances in diagnosis and treatment, there is still a need for more effective treatments to improve outcomes for patients with this condition. Therefore, we aim to review the current and future therapeutics reported in the literature and among ongoing clinical trials recruiting patients with CA.Keywords: cardiac amyloidosis, ATTR CA, transthyretin amyloidosis, AL CA, light-chain amyloidosis, management, treatment, stem cell transplantation, chemotherapy, immunomodulatory agents

Shuang Xu,1 Yi Fu,2 Dan Xu,1 Shuang Han,1 Mingzhi Wu,3 Xinrong Ju,1 Meng Liu,1 De-Sheng Huang,4,5 Peng Guan4,6 1Library of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Library of Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 4Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People’s Republic of China; 5Department of Intelligent Computing, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: De-Sheng Huang; Peng Guan, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China, Email dshuang@cmu.edu.cn; pguan@cmu.edu.cnBackground: Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH).Methods: PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots.Results: Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected.Conclusion: This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.Keywords: multidrug-resistant tuberculosis, pulmonary tuberculosis, medication trends, specific semantic types, MeSH tree, pubMR

Lei Zhang,1,&ast; Honglin Li,1,&ast; Liang Zhang,2 Zhihui Zu,1 Dinglin Xu,1 Jianwei Zhang1,2 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Gynecology, Obstetrics and Reproductive Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianwei Zhang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42, Wenhua West Road, Jinan, Shandong Province, People’s Republic of China, Tel +8653168901404, Email zhangjianwei1970@sina.comPurpose: Yangjing Zhongyu Tang (YJZYT) is a classic Chinese prescription for infertility treatment and exerts therapeutic effects via activity on the thin endometrium (TE). However, the major components and underlying mechanisms of YJZYT actions remain to be established. The main objectives of this study were to clarify the effects of YJZYT on the TE and provide insights into the related mechanisms based on network pharmacology and molecular docking analyses.Methods: Network pharmacology was employed to explore the main bioactive components and targets of YJZYT. TE-related genes were obtained from the Genecards database and screened for intersections with YJZYT. The Cytoscape 3.8.2 was used to build a “compounds-disease-targets” network and molecular docking analysis performed on key targets. The mechanism of action of YJZYT was further validated in vivo using a rat model.Results: A total of 98 YJZYT active ingredients, 2409 thin endometrium-associated genes, and 186 common targets were obtained. Through topological analysis, 10 core objectives were screened. Data from the PPI network suggest that AKT1, TNF, VEGFA, IL-6, TP53, INS, ESR1, MMP9, ALB, and ACTB serve as key targets in the action of YJZYT on TE. PI3K-Akt, TNF, apoptosis, IL-17 and MAPK were established as the main functional pathways. Molecular docking analysis revealed high affinity of the active ingredients of YJZYT, specifically, ursolic acid, palbinone, stigmasterol, and beta-sitosterol, for TNF, VEGFA, IL-6, AKT, and MMP9. YJZYT improved endometrial recovery, promoted endometrial angiogenesis, and upregulated protein expression of VEGF, PI3K, AKT, and p-AKT in the TE rat model.Conclusion: Network pharmacological and animal studies facilitated the prediction and validation of the active components and key targets of YJZYT potentially contributing to TE. Preliminary evidence from in vivo experiments showed that YJZYT promotes angiogenesis and thin endometrial repair via regulation of the PI3K/AKT pathway, providing a reference for further research.Keywords: network pharmacology, molecular docking, Yangjing Zhongyu Tang, thin endometrium, PI3K/AKT signaling pathway

Dujuan Xu,1,&ast; Ying Liu,1,&ast; Chao Xu,2,&ast; Xuekui Liu,3 Ye Chen,1 Chunguang Feng,4 Nan Lyu1 1Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 2Department of Radiology, Xuzhou Children’s Hospital, Xuzhou, People’s Republic of China; 3Department of Central Laboratory, Xuzhou Central Hospital, Xuzhou, People’s Republic of China; 4Department of Cardiology, Xuzhou Central Hospital, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Lyu; Chunguang Feng, Email kksfm8833@qq.com; fcg999@163.comObjective: To determine the factors influencing proximal radial artery occlusion (PRAO) right radial artery after coronary intervention.Methods: This is a single-center prospective observational study. A total of 460 patients were selected to undergo coronary angiography (CAG) or percutaneous coronary intervention (PCI) via the proximal transradial approach (PTRA) or distal transradial approach (DTRA). The 6F sheath tube were received by all patients. Radial artery ultrasound was performed 1 day before procedure and 1– 4 days after procedure. Patients were divided into the PRAO group (42 cases) and the non-PRAO group (418 cases). General clinical data and preoperative radial artery ultrasound indexes of the two groups were compared to analyze related factors leading to PRAO.Results: The total incidence of PRAO was 9.1%, including 3.8% for DTAR and 12.7% for PTRA. The PRAO rate of DTRA was significantly lower than that of PTRA (p < 0.05). Female, low body weight, low body mass index (BMI) and CAG patients were more likely to develop PRAO after procedure (p < 0.05). The internal diameter and cross-sectional area of the distal radial artery and proximal radial artery were smaller in the PRAO group than in the non-PRAO group, and the differences were statistically significant (p < 0.05). Multifactorial model analysis showed that the puncture approach, radial artery diameter and procedure type were predictive factors of PRAO, and the receiver operating characteristic curve showed a good predictive value.Conclusion: A larger radial artery diameter and DTRA may reduce the incidence of PRAO. Preoperative radial artery ultrasound can guide the clinical selection of appropriate arterial sheath and puncture approach.Keywords: proximal radial artery occlusion, coronary intervention, ultrasound, influencing factors, the distal transradial approach

Ling Tong,1,2,&ast; Shan Wang,1,2,&ast; Ranran Zhang,1,2 Yibo Wu,1 Dewu Xu,3 Ling Chen2 1Human Reproductive and Genetic Center, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 2Department of Breast Surgery, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Department of Medicine Education, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dewu Xu, Department of Medicine Education, Affiliated Hospital of Jiangnan University, Wuxi, 214062, People’s Republic of China, Email xdw@jiangnan.edu.cn Ling Chen, Department of Breast Surgery, Affiliated Hospital of Jiangnan University, Wuxi, 214062, People’s Republic of China, Email rainbow_lyn@163.comPurpose: To investigate the predictive value of systemic immune-inflammation-index (SII) and Pan-Immune-Inflammation-value (PIV) for axillary lymph node (ALN) metastasis in patients with breast cancer.Patients and Methods: We retrospectively collected data of 247 patients with invasive breast from the Affiliated Hospital of Jiangnan University. The state of axillary lymph node (ALN) metastasis was confirmed by pathological diagnosis. Clinicopathological data (age, ER, PR, HER2, Ki67 expression levels, diapause status, weight, histological grade, vascular invasion, and state of axillary lymph node) were compared between differences of SII and PIV groups and an association between clinical indexes and ALN metastasis was evaluated.Results: The cut-off values of SII and PIV were 320.04 and 92.01, respectively. The significant difference between vascular invasion (P=0.023) and axillary lymph node metastases (P< 0.001) in the high and low SII levels. Significant differences were observed in tumor size (p=0.024), PR expression level (P=0.033) and the status of axillary lymph node metastases (p< 0.001) between the high PIV group and the low PIV group. Univariate analysis showed that vascular invasion, tumor size, Ki67 expression level, SII, and PIV were significantly correlated with axillary lymph node metastases (p< 0.05). Then, multivariate analysis revealed that the vascular invasion (p< 0.001), HER2 expression levels (p< 0.047), SII (p< 0.001) and PIV (p< 0.030) were risk factors for axillary lymph node metastases.Conclusion: High levels of SII, PIV, LVI, and HER2 are the risk factors for axillary lymph node metastases in breast cancer patients.Keywords: breast cancer, systemic immune-inflammation-index, axillary lymph node metastases, pan-immune-inflammation-value

Ye Song,1 Jiangjun Mei,1 Dongwei Xu,2 Ying Ma1 1Department of Ultrasonography, Shanghai Pudong New Area Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Tel +86 13818086439, Email songye@tongji.edu.cnBackground: Ultrasound can assess renal perfusion, but its role in the evaluation of acute kidney injury (AKI) is still unclear. This prospective cohort study was to investigate the value of contrast-enhanced ultrasound (CEUS) in the evaluation of AKI in intensive care unit (ICU) patients.Methods: Fifty-eight patients were recruited from ICU between October 2019 and October 2020, and CEUS was used to monitor the renal microcirculation perfusion within 24h after admission. Parameters included rise time (RT), time to peak intensity (TTP), amplitude of peak intensity (PI), area under the curve (AUC), time from peak to one half (TP1/2) of renal cortex and medulla. Ultrasonographical findings, demographics, laboratory, etc were collected for further analysis.Results: There were 30 patients in the AKI group and 28 patients in the non-AKI group. The TTP, PI, TP1/2 of the cortex and the RT, TTP, TP1/2 of the medulla in the AKI group were significantly longer than in the non-AKI group (P < 0.05);. The TTP (OR = 1.261, 95% CI: 1.083– 1.468, P = 0.003) (AUCs 0.733, Sen% 83.3, Spe%57.1), TP1/2 (OR = 1.079, 95% CI: 1.009– 1.155, P = 0.027) (AUCs 0.658, Sen% 76.7, Spe%50.0) of the cortex and RT (OR = 1.453, 95% CI: 1.051– 2.011, P = 0.024) (AUCs 0.686, Sen% 43.3, Spe%92.9) of the medulla were related to the AKI. Eight new-onset AKI cases occurred in the non-AKI group within 7 days, the RT, TTP, TP1/2 of the cortex and medulla were significantly longer in the new-onset AKI group than in the non-AKI group (P < 0.05), but serum creatinine and blood urea nitrogen were no differences between groups (P > 0.05).Conclusion: This study indicates CEUS can assess the renal perfusion in AKI. TTP and TP1/2 of the cortex and RT of the medulla can aid the diagnosis of AKI in ICU patients.Keywords: contrast-enhanced ultrasound, acute kidney injury, intensive care unit

Yan Teng,1 Danfeng Xu,1 Xianhong Yang,1 Hui Tang,2 Xiaohua Tao,1 Yibin Fan,1,&ast; Yang Ding1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Ding; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13732261339 ; +86-13505811700, Email dingyang@hmc.edu.cn; taoxiaohua@hmc.edu.cnAbstract: Unlike apoptosis, pyroptosis, necroptosis, and ferroptosis are recently identified modes of programmed cell death (PCD) with unique molecular pathways. Increasing evidence has indicated that these PCD modes play a crucial role in the pathogenesis of various non-malignant dermatoses (a group of cutaneous disorders), including infective dermatoses, immune-related dermatoses, allergic dermatoses, benign proliferative dermatoses, etc. Moreover, their molecular mechanisms have been suggested as potential therapeutic targets for the prevention and treatment of these dermatoses. In this article, we aim to review and summarize the molecular mechanisms of pyroptosis, necroptosis, and ferroptosis and their roles in the pathogenesis of some non-malignant dermatoses.Keywords: pyroptosis, necroptosis, ferroptosis, molecular mechanisms, non-malignant dermatoses

Yuandi Wang,1,2,&ast; Lijuan Xing,2,&ast; Lexiu Deng,1,2 Xinsheng Wang,2 Dandan Xu,2 Bu Wang,2 Zhihua Zhang2,&ast; 1Graduate School, Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China; 2Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihua Zhang, Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People’s Republic of China, Tel +86 0313 8033598, Email zzh19641229@163.comPurpose: The efficacy of immunotherapy for non-small cell lung cancer (NSCLC) is limited owing to cold tumors and drug resistance. Therefore, it is important to identify the molecular mechanisms underlying immune evasion in NSCLC. Spontaneous ferroptosis of neutrophils has been suggested as a key mechanism of immunosuppression in cancer. Insulin-like growth factor binding protein 1 (IGFBP1) plays an important role in immune infiltration in several cancers. However, the role of IGFBP1 in NSCLC is unknown. Therefore, in this study, we aimed to investigate the association of IGFBP1 mRNA expression with infiltration of myeloid-derived suppressor cells and prognosis in NSCLC.Patients and Methods: Retrospective RNA-seq data from 990 patients in the Cancer Genome Atlas (TCGA) database were analyzed in relation to patient clinical characteristics. The Timer2 database was used to assess immune infiltration, and the FerrDb V2 database was used to obtain ferroptosis-related genes. Finally, the results were validated by the proteomic analysis of serum samples collected from six patients with NSCLC and six healthy individuals.Results: IGFBP1 expression was enriched in lung adenocarcinoma samples and positively correlated with the pathological grade of NSCLC. IGFBP1 expression was an independent prognostic factor for the overall survival of patients with NSCLC. In addition, IGFBP1 expression correlated with myeloid-derived suppressor cell infiltration. Notably, Gene Ontology analysis of IGFBP1-related genes revealed that the major molecular functions of their protein products were related to NADP+ 1-oxidoreductase activity. Furthermore, expression levels of multiple ferroptosis suppressor genes positively correlated with IGFBP1 expression.Conclusion: High IGFBP1 expression indicates a poor prognosis in patients with NSCLC, which may be related to tumor immunosuppression caused by neutrophil ferroptosis.Keywords: immune infiltration, immunotherapy, lung adenocarcinoma, lung squamous cell carcinoma, myeloid-derived suppressor cells

Lijuan Xu,1 Fengsen Li,2 Min Jiang,2 Zheng Li,2 Dan Xu,2 Jing Jing,2 Jing Wang,2 Jianbing Ding3 1The Fourth Clinical Medical College, Xinjiang Medical University, Urumqi, People’s Republic of China; 2Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Jing Wang, Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999908413, Email jingw_xj@163.com Jianbing Ding, Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999847738, Email 1601379937@xjmu.edu.cnBackground: The interaction between immune checkpoint and myeloid-derived suppressor cells (MDSCs) play a significant role in inflammatory diseases. But their correlation with chronic obstructive pulmonary disease (COPD) remains unclear.Methods: The differentially expressed immune checkpoints and immunocytes in the airway tissues of COPD patients were identified by bioinformatics analysis, followed by correlation analysis and identification of immune-related differential genes for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. The results of bioinformatics analysis were verified by ELISA and Real-Time PCR and transcriptome sequencing of the peripheral blood of both COPD patients and healthy subjects.Results: The results of the bioinformatics analysis showed that the level of MDSCs in airway tissue and peripheral blood of COPD patients was higher than that of healthy controls. The expression of CSF1 in airway tissue and peripheral blood of COPD patients increased, and CYBB was increased in airway tissue and decreased in peripheral blood of COPD patients. The expression of HHLA2 in the airway tissue decreased in COPD patients, and showed a negative correlation with MDSCs, with a correlation coefficient of − 0.37. The peripheral blood flow cytometry results indicated that MDSCs and Treg cells of COPD patients were higher than those in the healthy control group. The results of peripheral blood ELISA and RT-PCR showed that the HHLA2 and CSF1 levels in COPD patients were higher than those in the healthy control group.Conclusion: In COPD, the bone marrow is stimulated to produce MDSCs, and a large number of MDSCs migrate to airway tissue through peripheral blood and cooperate with HHLA2 to exert an immunosuppressive effect. Whether MDSCs play an immunosuppressive effect during migration needs to be further confirmed.Keywords: chronic obstructive pulmonary disease, COPD, myeloid-derived suppressor cell, MDSC, immunosuppression, human endogenous retrovirus-H long terminal repeat-associating protein 2, HHLA2, bioinformatics analysis

Meiyuan Dong,1,2 Huiling Chen,2 Song Wen,2 Yue Yuan,2 Liling Yang,2 Yanyan Li,2 Xinlu Yuan,2 Dongxiang Xu,2 Ligang Zhou1– 3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comAbstract: With the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the treatment of type 2 diabetes mellitus (T2DM) has achieved a new milestone, of which the insulin-independent mechanism could produce weight loss, improve insulin resistance (IR) and exert other protective effects. Besides the well-acknowledged biochemical processes, the dysregulated balance between sympathetic and parasympathetic activity may play a significant role in IR and obesity. Weight loss caused by SGLT-2i could be achieved via activating the liver–brain–adipose neural axis in adipocytes. We previously demonstrated that SGLT-2 are widely expressed in central nervous system (CNS) tissues, and SGLT-2i could inhibit central areas associated with autonomic control through unidentified pathways, indicating that the role of the central sympathetic inhibition of SGLT-2i on blood pressure and weight loss. However, the exact pathway of SGLT2i related to these effects and to what extent it depends on the neural system are not fully understood. The evidence of how SGLT-2i interacts with the nervous system is worth exploring. Therefore, in this review, we will illustrate the potential neurological processes by which SGLT2i improves IR in skeletal muscle, liver, adipose tissue, and other insulin-target organs via the CNS and sympathetic nervous system/parasympathetic nervous system (SNS/PNS).Keywords: sodium-glucose cotransporter 2 inhibitors, central nervous system, autonomic nervous system, insulin resistance, weight loss

Meiyuan Dong,1,2 Huiling Chen,2 Song Wen,2 Yue Yuan,2 Liling Yang,2 Dongxiang Xu,2 Ligang Zhou1– 3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang@yahoo.comAbstract: Hyperuricemia is a common comorbidity in patients with type 2 diabetes mellitus (T2DM), as insulin resistance (IR) or hyperinsulinemia is associated with higher serum uric acid (SUA) levels due to decreased uric acid (UA) secretion, and SUA vice versa is an important risk factor that promotes the occurrence and progression of T2DM and its complications. Growing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a novel anti-diabetic drug initially developed to treat T2DM, may exert favorable effects in reducing SUA. Currently, one of the possible mechanisms is that SGLT2i increases urinary glucose excretion, probably inhibiting glucose transport 9 (GLUT9)-mediated uric acid reabsorption in the collecting duct, resulting in increased uric acid excretion in exchange for glucose reabsorption. Regardless of this possible mechanism, the underlying comprehensive mechanisms remain poorly elucidated. Therefore, in the present review, a variety of other potential mechanisms will be covered to identify the therapeutic role of SGLT-2i in hyperuricemia.Keywords: hyperuricemia, uric acid, type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors

Hongchen Zhang,1– 3,&ast; Shanshan Hu,1– 3,&ast; Dongchao Xu,1– 3 Hongzhang Shen,1– 3 Hangbin Jin,1– 3 Jianfeng Yang,1– 3 Xiaofeng Zhang1– 3 1The Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 2Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Zhejiang, People’s Republic of China; 3Hangzhou Institute of Digestive Disease, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Zhang, Department of Gastroenterology, Hangzhou First People’s Hospital, NO. 261 HuanSha Road, Hangzhou, 310006, People’s Republic of China, Tel +86-13588296257, Fax +86-571-56005600, Email moonshadowing@126.comBackground: With the increasing number of critically ill patients in the gastroenterology department (GED), infections associated with Carbapenem resistant gram-negative bacteria (CR-GNB) are of great concern in GED. As the turn-around time (TAT) for a positive screening culture result is slow, contact precaution and pre-emptive isolation, cohorting methods should be undertaken immediately on admission for high-risk patients. Accurate prediction tools for CR-GNB colonization in GED can help determine target populations upon admission. And thus, clinicians and nurses can implement preventive measures more timely and effectively.Objective: The purpose of the current study was to develop and internally validate a CR-GNB carrier risk predictive nomogram for a Chinese population in GED.Methods: Based on a training dataset of 400 GED patients collected between January 2020 and December 2021, we developed a model to predict CR-GNB carrier risk. A rectal swab was used to evaluate the patients’ CR-GNB colonization status microbiologically. We optimized features selection using the least absolute shrinkage and selection operator regression model (LASSO). In order to develop a predicting model, multivariable logistic regression analysis was then undertaken. Various aspects of the predicting model were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping.Results: The prediction nomogram includes the following predictors: Transfer from another hospital (Odds ratio [OR] 3.48), High Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.61), Longterm in healthcare facility (OR 10.94), ICU admission history (OR 9.03), Blood stream infection history (OR 3.31), Liver cirrhosis (OR 4.05) and Carbapenem usage history within 3 month (OR 2.71). The model demonstrated good discrimination and good calibration.Conclusion: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can take more timely infection preventive measures on isolation, cohorting and medical interventions.Keywords: carbapenem resistant gram-negative bacteria, carrier risk, gastroenterology department, predictive nomogram, screen culture

Ma-Chao Li,1,&ast; Xiao-Yue Wang,1,&ast; Tong-Yang Xiao,2,&ast; Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutation

Dong Xu,1 Xu Zhu,2 Junyu Huo,2 Xupin Xie,1 Changpin Huang,1 Xin Fang,1 Ting Yin3 1Department of Vascular Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University, First Affiliated Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ting Yin, Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13777879077, Fax +86 56005600, Email ameliyt@163.com Xin Fang, Department of Vascular, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 13867478324, Fax +86 56005600, Email fangxin324@hotmail.comPurpose: Peripheral arterial disease (PAD) presenting with underlying hypertension (HTN) poses a higher risk of bilateral lower limb amputation than PAD patients without HTN. While the role of HTN management of PAD patients has received limited attention. We analyzed the clinical characteristics of PAD in adults with HTN and explored risk factors for PAD to construct a nomogram for evaluating critical limb ischemia (CLI) and lesion severity.Methods Patients and Methods: Between January 2014 and December 2019, we retrospectively evaluated 1886 patients with peripheral artery disease with coexisting HTN. Patients were randomly divided into training (n = 1320, 70%) and validation cohorts (n = 566, 30%), and according to the subjective experience of PAD [Fontaine classification (I–II vs III–IV)], patients were further classified into intermittent claudication (IC) and CLI groups. LASSO regression and multivariate Cox proportional hazard analyses were used to construct a nomogram using variables defined in the training cohort, which was validated in the validation cohort. The evaluation of the predictive discriminative, accuracy and clinical application are further analyzed.Results: In the training cohort, optimal independent factors included age, male sex, body mass index, diabetes mellitus, heart rate, triglyceride, and uric acid (AM-BDHTU), which were included in the nomogram predicting the CLI risk (all P < 0.05). The C-index values for CLI risk in PAD with HTN patients were 0.729 (95% CI: 0.704– 0.807) and 0.728 (95% CI: 0.652– 0.744) in the training and validation sets, respectively. Calibration curves indicated good consistency between predicted and actual outcomes. DCA confirmed the clinical utility of the diagnostic model.Conclusion: The AM-BDHTU nomogram, constructed and validated using simple to obtain clinical variables, when combined with the Fontaine classification, effectively predicts the risk of CLI among PAD patients with HTN.Keywords: peripheral arterial disease, hypertension, vascular-related complications, LASSO regression, nomogram, predictive diagnosis