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Ruiwei Guo,1,2 Jin Wu,1,2 Yanmin Zheng,1,2 Xiaona Lin,1,2 Zelin Zhuang,1,2 Jingjing Yin,1,2 Zhirong Lin,1 Lei Xie,1,2 Shuhua Ma1,2 1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Laboratory of Medical Molecular Imaging, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Shuhua Ma; Lei Xie, Email shuhua6633@163.com; 13lxie1@stu.edu.cnBackground: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood.Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison.Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT.Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.Keywords: inflammatory bowel disease, graph theory, visuospatial working memory, cognitive impairment, mental rotation task

Li Ren, Zhaoling Li, Ji Wu, Lian Duan, Jialiang Gao Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Li Ren, Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Address: No. 5, Beixiange, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86 18600697916, Email renlirl7961@hotmail.comObjective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities.Methods: This web-based study was carried out between April 2023 and September 2023 at Guang’anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities.Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97± 5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34± 2.29 (possible range: 0– 9), 35.24± 4.99 (possible range: 9– 45), and 27.79± 10.09 (possible range: 9– 45), respectively. The structural equation model demonstrated that elderly CHD patients’ knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P< 0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P< 0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P< 0.001), cardiac function directly affects knowledge with path coefficient of − 0.97 (P< 0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P< 0.001).Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.Keywords: knowledge, attitudes, practices, cross-dimensional study, coronary heart disease, self-perceived health abilities

Jie Wu,1 Yingzhuo Ma,1 Jun Wang,1 Mingzhao Xiao2 1Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Mingzhao Xiao, Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email xmz.2004@163.com Jun Wang, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email smile@stu.cqmu.edu.cnPurpose: ChatGPT has a wide range of applications in the medical field. Therefore, this review aims to define the key issues and provide a comprehensive view of the literature based on the application of ChatGPT in medicine.Methods: This scope follows Arksey and O’Malley’s five-stage framework. A comprehensive literature search of publications (30 November 2022 to 16 August 2023) was conducted. Six databases were searched and relevant references were systematically catalogued. Attention was focused on the general characteristics of the articles, their fields of application, and the advantages and disadvantages of using ChatGPT. Descriptive statistics and narrative synthesis methods were used for data analysis.Results: Of the 3426 studies, 247 met the criteria for inclusion in this review. The majority of articles (31.17%) were from the United States. Editorials (43.32%) ranked first, followed by experimental studys (11.74%). The potential applications of ChatGPT in medicine are varied, with the largest number of studies (45.75%) exploring clinical practice, including assisting with clinical decision support and providing disease information and medical advice. This was followed by medical education (27.13%) and scientific research (16.19%). Particularly noteworthy in the discipline statistics were radiology, surgery and dentistry at the top of the list. However, ChatGPT in medicine also faces issues of data privacy, inaccuracy and plagiarism.Conclusion: The application of ChatGPT in medicine focuses on different disciplines and general application scenarios. ChatGPT has a paradoxical nature: it offers significant advantages, but at the same time raises great concerns about its application in healthcare settings. Therefore, it is imperative to develop theoretical frameworks that not only address its widespread use in healthcare but also facilitate a comprehensive assessment. In addition, these frameworks should contribute to the development of strict and effective guidelines and regulatory measures.Keywords: ChatGPT, large language model, medicine, nursing, scoping review, bibliometric analysis

Jiayan Li,1,&ast; Jie Ding,1,&ast; Haoyang Wu,1 Chenyan Lu,1 Jian Wu,2 Qianqian Luo1 1Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, Nantong, 226019, People’s Republic of China; 2Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wu, Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, People’s Republic of China, Tel +86-21-54601295, Email jianwu12@fudan.edu.cn Qianqian Luo, Department of Hypoxic Biomedicine, Institute of Special Environmental Medicine and Coinnovation Center of Neuroregeneration, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, 226019, People’s Republic of China, Tel +86-513-85503378, Email qianqianluo@ntu.edu.cnBackground: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite.Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin–eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue.Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated.Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.Keywords: frostbite, Tat-CIRP, inflammation, angiogenesis

Qiu Huang,&ast; Yue Ge,&ast; Yu He, Jian Wu, Yonghua Tong, Haojie Shang, Xiao Liu, Xiaozhuo Ba, Ding Xia, Ejun Peng, Zhiqiang Chen, Kun Tang Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiqiang Chen; Kun Tang, Email zhqchen8366@163.com; tangsk1990@163.comAbstract: Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.Keywords: nanoparticles, cancer therapy, cancer-associated fibroblasts, drug delivery, cancer, nanomedicine

Xiaoying Meng,1,2 Fei Li,2 Wenpei Wu,3 Juncang Wu1,2 1Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical College, Hefei, Anhui, 230011, People’s Republic of ChinaCorrespondence: Juncang Wu, Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China, Email wujuncang126@126.comPurpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction.Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained.Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p< 0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p< 0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%).Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.Keywords: ischemic stroke, carotid plaque, spectral CT, effective atomic number, iodine density values, anhydrous iodine values, electron density

Guanjin He,1,&ast; Qifeng Yang,2,&ast; Yuyang Shen,3 Lanzhi Zhang,2 Jingping Wu,2 Hongbin Cheng1 1Dermatology Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Medical Aesthetic Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Traditional Chinese Medicine Department, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Wu; Hongbin Cheng, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shi-Er-Qiao Road, Jinniu District, Chengdu, People’s Republic of China, Tel +86 15928747715 ; +86 13880848134, Email jingpingwu2022@163.com; chenghongbin@cdutcm.edu.cnAbstract: Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.Keywords: facial wound repair, modified kite flap, experience, case series

Wen Wang,1,2,&ast; Junrong Ye,1,&ast; Yanheng Wei,3,&ast; Lexin Yuan,3 Jialan Wu,1 Zhichun Xia,4 Jiawei Huang,1 Haoyun Wang,2 Zezhi Li,4 Jianxiong Guo,5 Aixiang Xiao3 1Geriatric Neuroscience Center, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China; 2School of Nursing, Guangzhou Medical University, Guangzhou, Guangdong, 510182, People’s Republic of China; 3Department of Nursing, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China; 4Adult Psychiatry Department, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China; 5Department of Chronic Diseases, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aixiang Xiao, Department of Nursing, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China, Tel +86 18922165267, Email 543061910@qq.com Zezhi Li, Adult Psychiatry Department, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510370, People’s Republic of China, Tel +86 13564648631, Email biolpsychiatry@126.comBackground: Workplace violence (WPV) had become an important issue that endangered the occupational safety of psychiatric nurses. A growing number of studies showed positive post-traumatic growth (PTG) resulting from coping with trauma.Objective: To investigate the characteristics of PTG in psychiatric nurses who experienced violence in the workplace and analyze its influencing factors.Methods: A total of 1202 psychiatric nurses participated in the study. From October 2022 to December 2022, this cross-sectional study collected data on psychiatric nurses from five tertiary hospitals in Guangdong Province, China. Twenty-item Chinese version post-traumatic growth inventory (PTGI), Jefferson Scale of Empathy Health Professional (JSE-HP), Confidence in Coping with Patient Aggression Instrument (CCPAI), Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C), and Connor-Davidson Resilience Scale (CD-RISC) measured PTG level, empathy, the confidence in coping with WPV, post-traumatic stress disorder, and resilience, respectively. Bivariate analysis and multiple linear regression explored potential influencing factors of PTG. This study complies with the EQUATOR (STROBE) checklist.Results: The sample was composed of a total of 1202 psychiatric nurses suffering from WPV. The average score of PTGI in psychiatric nurses was above average (65.75 points; SD = 20.20). Linear regression analyses showed from single-child family (β=0.052,95% CI=0.342,5.409, P< 0.05), education background (β=0.108,95% CI=1.833,5.097, P< 0.001), the confidence in coping with patient aggression (β=0.106,95% CI=1.385,4.317, P< 0.001), empathy (β=0.057,95% CI=0.312,4.374, P< 0.05), and resilience (β=0.484,95% CI=7.737,9.575, P< 0.001) were associated with PTG level.Conclusion: Psychiatric nurses who were non-single child, had received higher education, had confidence in coping with patient aggression, had good resilience and strong empathy were prone to PTG after experiencing WPV. The study findings could help hospitals and nursing managers identify vulnerable individuals and take early intervention measures against such populations.Keywords: post-traumatic growth, psychiatric nurses, workplace violence, mental health

Shasha Zhang,1,&ast; Jianhua Wu,2,&ast; Yue Zhao,3 Jingjing Zhang,1 Xiaoyun Zhang,1 Chensi Wu,3 Zhidong Zhang,4 Zhanjun Guo1 1Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 4Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Zhang, Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Email zzd407@163.com Zhanjun Guo, Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095734, Email zjguo5886@aliyun.comPurpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy

Zhiliang Zhang,1,&ast; Zhongxiang Ding,2,&ast; Fenyang Chen,2 Rui Hua,3 Jiaojiao Wu,3 Zhefan Shen,2 Feng Shi,3 Xiufang Xu1 1School of Medical Imaging, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shi; Xiufang Xu, Email feng.shi@uii-ai.com; 1996033011@hmc.edu.cnBackground: Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors.Methods and results: We recruited 211 lacunar stroke patients and 83 control patients. The patients’ cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC> 0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P< 0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P< 0.05).Conclusion: Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.Keywords: lacunar stroke, cerebral small vessel disease, imaging markers, deep learning, quantification, image segmentation, clinical risk factors

Xingqiang Wang,1,2,&ast; Xianna Yang,3,&ast; Shiqi Wang,3,&ast; Xiaofang Tian,1 Jianmei Yin,3 Nian Liu,3 Pengtao Di,1 Jipeng Qi,3 Ya Li,3 Jimin Chen,3,4 Yang Wu,1 Jingjin Wu,1,2 Weiqing Zhao,5 Jiangyun Peng,1,2 Ling Zhang,1,2 Lingli Gu1 1Department of Rheumatology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 2Yunnan Provincial Clinical Medicine Research Center of Rheumatism in TCM, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 3The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650021, People’s Republic of China; 4Department of Integrative Internal Medicine, The Lijiang Hospital of Traditional Chinese Medicine, Lijiang, Yunnan, 674100, People’s Republic of China; 5Department of Rheumatology and Immunology, The First People’s Hospital of Yunnan Province and The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhang; Lingli Gu, Email zebaiyuan@126.com; guyuxin82@126.comAbstract: Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).Keywords: rheumatoid arthritis, glucocorticoids tapering, clinical trial, traditional Chinese medicine, Yupingfeng Guizhi Decoction, Juanbi Decoction

Wenpei Wu,1,2,&ast; Zhi Geng,3– 5,&ast; Aimei Wu,2,&ast; Xinyi Chen,6,7 Xiaoying Meng,2 Qianyun Zhang,2 Zheng Tan,2 Hong Yue,2 Juncang Wu1,2 1Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of Neurology, Hefei Second People’s Hospital, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 5Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, 230000, People’s Republic of China; 6Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 7The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juncang Wu; Hong Yue, Intersection of Guangde Road and Leshui Road, Hefei, Anhui, 230011, People’s Republic of China, Tel/Fax +86 551 13956076148 ; +86 551 18949855780, Email wujuncang126@126.com; yuehong01@foxmail.comBackground and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH).Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients.Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 μmol/L) than those with poor prognosis (393.06 ± 148.46 μmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 μmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients.Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.Keywords: intracerebral hemorrhage, uric acid, oxidative stress, follow-up, nonlinear relationship, prognosis

Yang Li,1,&ast; Yuling Sun,1,&ast; Ji Wu,1,&ast; Zhongya Gao,1 Youcai Qiu,1 Lin Han,2 Xuhua Lu1 1Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuhua Lu, Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86-21-81885793, Email xuhualu415@163.com Lin Han, Department of Orthopaedics, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email hanlin1018@163.comBackground and Aim: Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage.Methods: The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system.Results: A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system’s sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%.Conclusion: The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries.Keywords: cervical hyperextension injury, anterior longitudinal ligament injury, cervical spine trauma, scoring system

Kuihan Tang,1 Li Sun,2 Long Chen,2 Xiaobo Feng,1 Jiarui Wu,2 Hao Guo,2 Yong Zheng1 1Department of Orthopedics, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, 550014, People’s Republic of China; 2Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, 550000, People’s Republic of ChinaCorrespondence: Yong Zheng, Email 1210244258@qq.comBackground: Mitochondrial autophagy is closely related to the pathogenesis of osteoarthritis, In order to explore the role of mitochondrial autophagy related genes in knee osteoarthritis (KOA) and its molecular mechanism.Methods: KOA-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR.Results: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis.Conclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.Keywords: Gene Expression Omnibus, diagnostic, bioinformatics analysis, immune infiltration, biomarkers

Chuanhao Xiong,1,&ast; Jingzhu Wu,1,&ast; Yuhang Ma,1,&ast; Na Li,1 Xuejiao Wang,1 Yao Li,2 Xiaoying Ding1 1Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Ding, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Email xiaoyingding@126.com Yao Li, Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, People’s Republic of China, Email yao.li@shsmu.edu.cnPurpose: Polycystic ovary syndrome (PCOS) is a frequent cause of infertility in reproductive-age women. Our work aims to evaluate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on gut microbiota, with metabolic parameters including body weight and the hormone profile in PCOS.Patients and Methods: Dehydroepiandrosterone (DHEA)-induced PCOS mice were established and then treated with two GLP-1RAs: liraglutide and novel form semaglutide for four weeks. Changes in body weight and metabolic parameters were measured. Fecal samples were collected and analyzed using metagenomic sequencing.Results: Liraglutide and semaglutide modulated both alpha and beta diversity of the gut microbiota in PCOS. Liraglutide increased the Bacillota-to-Bacteroidota ratio through up-regulating the abundance of butyrate-producing members of Bacillota like Lachnospiraceae. Moreover, liraglutide showed the ability to reverse the altered microbial composition and the disrupted microbiota functions caused by PCOS. Semaglutide increased the abundance of Helicobacter in PCOS mice (p < 0.01) which was the only bacteria found negatively correlated with body weight. Moreover, pathways involving porphyrin and flavonoids were increased after semaglutide intervention.Conclusion: Liraglutide and semaglutide improved reproductive and metabolic disorders by modulating the whole structure of gut microbiota in PCOS. The greater efficacy in weight loss compared with liraglutide observed after semaglutide intervention was positively related with Helicobacter. The study may provide new ideas in the treatment and the underlying mechanisms of GLP-1RAs to improve PCOS.Keywords: PCOS, GLP-1 receptor agonists, gut microbiota, metabolism

Tong Bao,1,&ast; Liru Qin,2,&ast; Guimei Hou,1 Hongmei Jiang,1 Lifeng Wang,1 Ying Wang,1 Junhui Wu,1 Jinli Wang,3 Yunlei Pang4 1Department of Ophthalmological Examination, Chifeng Chaoju Eye Hospital, Chifeng, People’s Republic of China; 2Department of Ophthalmology, Inner Mongolia Baogang Hospital, Baotou, People’s Republic of China; 3Department of Cataract, Chifeng Chaoju Eye Hospital, Chifeng, People’s Republic of China; 4Department of Ophthalmic Plastic Surgery, Chifeng Chaoju Eye Hospital, Chifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinli Wang, Department of Cataract, Chifeng Chaoju Eye Hospital, Chifeng, People’s Republic of China, Email chaojueyewjl66@163.com Yunlei Pang, Department of Ophthalmic Plastic Surgery, Chifeng Chaoju Eye Hospital, Chifeng, People’s Republic of China, Email 29483645@qq.comObjective: To investigate the association between the peripheral refractive errors of the fundus in different regions and moderate and high myopia.Methods: In this case-control study, 320 children and adolescents aged 6 to 18 years were recruited. Peripheral refractive errors were measured using multispectral retinal refractive topography (MRT). Spherical equivalent (SE) and cylinder errors were classified into low, moderate, and high categories based on the magnitude range. Logistic regression was performed to test the factors associated with myopia.Results: There were 152 participants with low myopia and 168 participants with moderate and high myopia included in the current study. Participants with moderate and high myopia were most likely to be older, with larger axial length (AL), lower SE, less time to watch electronic devices on the weekend, a higher difference between central refractive error and paracentral refractive error from the superior side of the retina (RDV-S), but a smaller difference between the central refractive error and paracentral refractive error from the inferior side of the retina (RDV-I) than those with low myopia (all P < 0.05). After logistic analysis, female sex (odds ratio [OR] = 4.14; 95% confidence interval [CI] = 2.16– 7.97, P < 0.001), AL (OR = 6.88, 95% CI = 4.33– 10.93, P < 0.001), and RDV-I (OR = 0.52, 95% CI = 0.32– 0.86, P = 0.010) were independent factors for moderate and high myopia.Conclusion: Our study demonstrated that the retina peripheral refraction of the eyes (RDV-I) was associated with moderate and high myopia, and RDV-S was only associated with high myopia.Keywords: peripheral refractive errors, myopia, spherical equivalent, logistic analysis, ocular biometrics

Junhao Wu,&ast; Caihan Duan,&ast; Chaoqun Han, Xiaohua Hou Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoqun Han; Xiaohua Hou, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Email hcq1987912@hotmail.com; houxh@medmail.com.cnBackground: Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients.Methods: Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by “limma” were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein–protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated.Results: The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees.Conclusion: The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.Keywords: Eosinophilic esophagitis, pediatrics, bioinformatic analysis, machine-learning, potential diagnostic/therapeutic biomarker

At present, amorphous boron powder is considered to be the best fuel for solid fuel-rich propellants due to its extremely high volume calorific value and mass calorific value. Amorphous boron powder produced by magnesium thermal reduction contains many impurities that are insoluble in acids as well as defects such as low purity, excessive particle size, and poor chemical activity, which seriously hinder its large-scale application in the military and aerospace fields. In this paper, the soluble transformation mechanism of insoluble boron magnesium compounds into amorphous boron powder during calcination and a method for purification boron powder were studied. In order to remove insoluble boron magnesium compounds in amorphous boron powder, the insoluble impurities Mg5B2O5 and MgB4 were converted into soluble MgB4O7 and MgO during calcination. The samples were then subjected to either water leaching or acid leaching to convert the crude amorphous boron powder products into high-purity amorphous boron powder products. SEM-EDS, XRD, XPS, and other techniques were used to determine the occurrence states of the impurity phases. The transformation of impurity phases after calcining water leaching and acid leaching was monitored. The results showed that the magnesium content in the amorphous boron powder was reduced to 0.96%, and the purity of the boron powder was increased to 97.34% by subjecting the amorphous boron powder to a combined calcination technique and either water leaching or acid leaching treatment.

The recovery of iron phosphate from the leaching slag of used lithium iron phosphate cathode materials is a crucial step to achieve closed-loop recovery of lithium iron phosphate, which has not yet been effectively accomplished. In the study, ultrasonic-assisted sulfuric acid leaching was used to remove impurities in the iron phosphate, to meet the stringent impurity content requirements for battery-grade iron phosphate regarding impurity content. Optimization of leaching conditions involved a sulfuric acid concentration of 0.2 mol·L-1, acid-leaching time of 30 min, power of 50 W, and reaction temperature of 80℃. Under these conditions, the removal efficiencies of Cr, Cu, Ni, and Zn in iron phosphate were 26.09%, 83.0%, 75.9%, and 96.3%, respectively. Simultaneously, the content of impurity elements Cr and Zn concurred with the standard for battery-grade iron phosphate (HG/T 4701-2021), with both 50 ppm and 10 ppm contents. The leaching results indicated the effectiveness of ultrasound in enhancing the removal of impurity elements in iron phosphate within a sulfuric acid solution. Further analyses, including XRD, particle size, TEM, and XPS indicated that the surface of the iron phosphate particles cavitated after ultrasonic acid leaching, resulting in the formation of numerous pores. Additionally, particle collisions led to a reduction in particle size, with no generation of by-products during the process. This innovative approach not only contributed to the removal of impurity elements but also provided insights into the reuse of leaching slag (iron phosphate) and offered guidance for the recovery of metals from waste lithium iron phosphate cathode materials.

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

Xinyue Hu,1– 3 Beibei Wang,1– 3 Jing Chen,1– 3 Dong Han,1– 3 Jing Wu1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, People’s Republic of ChinaCorrespondence: Jing Wu, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-27-85351618, Email drjingwu@hust.edu.cnPurpose: Many studies have focused on the association between Autism spectrum disorder (ASD) and epidural labor analgesia (ELA), which is the most effective way to manage labor pain. The purpose of this meta-analysis was to summarize the current state of the association between ELA and ASD.Methods: A search of the literature yielded 201 relevant studies, of which 7 cohort studies met our inclusion criteria. Two independent reviewers screened the inclusion results, extracted data, and assessed the risk of bias and quality of evidence.Results: Compared to parturient who did not receive ELA, parturient who received ELA had a slightly increased risk of ASD (adjusted hazard ratio [aHR], 1.12; 95% confidence interval [CI], 1.06– 1.17; I2, 69%; P < 0.001; seven studies). After excluding one literature (aHR, 1.09; 95% CI, 1.06– 1.12; I2, 4%; P < 0.001; six studies). The sensitivity analyses had consistent outcomes with the main analyses involving siblings (aHR 1.11; 95% CI 1.03– 1.19), cesarean section and instrumental deliveries (aHR 1.07; 95% CI 1.03– 1.10), non-overlapping populations (aHR 1.09; 95% CI 1.05– 1.12), full-term birth populations (aHR 1.10; 95% CI 1.06– 1.14), and studies assessed to have moderate risk of bias (aHR 1.09; 95% CI 1.02– 1.16).Conclusion: This meta-analysis revealed a modest positive association between ELA and ASD, acknowledging a slight potential risk. However, it is important to note that this risk cannot be completely dismissed due to the possibility of bias and this association is based on low-quality evidence. Future studies are required to assess and mitigate different confounding biases and investigate the time-dose-response relationship.Keywords: Autism spectrum disorder, epidural analgesia, epidural labor analgesia, ELA, neuraxial labor analgesia, pregnancy, meta-analysis

Xin Yang,1,2,&ast; Zhikuan Xia,1,&ast; Yunlong Fan,1 Yitong Xie,1 Ge Ge,1 Dexiu Lang,3 Junhong Ao,1 Danxia Yue,1 Jiamin Wu,1 Tong Chen,1 Yuekun Zou,1 Mingwang Zhang,4 Rongya Yang1,2 1Department of Dermatology, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Department of Dermatology, Yanbian University Hospital, Yanji, People’s Republic of China; 3Department of Dermatology, XingYi People’s Hospital, Xingyi, People’s Republic of China; 4Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwang Zhang; Rongya Yang, Email mingwangzhang2@163.com; yangrya@sina.comBackground: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers.Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features.Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model’s classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs.Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells.Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.Keywords: solar lentigines, photoaging, diagnostic biomarkers, immune infiltration, artificial neural network

Cheng Peng, Yilin Xu, Jing Wu, Donghai Wu, Lili Zhou, Xinhua Xia School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Xinhua Xia; Lili Zhou, Email xiaxinhua001@hnucm.edu.cn; 004683@hnucm.edu.cnAbstract: The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.Keywords: nanoparticles, biomimetic delivery system, tumor therapy, cell membrane-coating

Hang Li, Xiping Shen, Ji Wu Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Ji Wu, Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, No. 2666, Ludang Road, Wujiang District, Suzhou, Jiangsu Province, People’s Republic of China, Tel +86-0512-82881248, Email 1968232851@qq.com

Ji Wu, Xiping Shen Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xiping Shen, Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Ludang Road, Wujiang District, Suzhou, Jiangsu Province, 2666, People’s Republic of China, Tel +86 0512-82881248, Email shenxiping2022@163.com

Liu M, Luo G, Wang Y, et al. Int J Nanomedicine. 2017;12:6827-6840. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 7B on page 6834 is incorrect. The authors have also advised the magnification in the note section is incorrect. The correct Figure 7 and caption are as follows. Figure 7 Fluorescence microscopy photographes of GFP transgenic fibroblasts on the (A) PCL/DA, (B) PCL/NS0.5, (C) PCL/NS1.0 and (D) PCL/NS2.0 films. (E) The cell viability measured using CCK8 assay at day 1, 3 and 5 post-seeding.Abbreviations: CCK8, Cell Counting Kit-8; DA, dopamine; GFP, green fluorescent protein; NS, nanosilver; PCL, polycaprolactone.Notes: Magnification ×100. *p

Wenjuan Yan,1,&ast; Jiaojiao Wu,2,&ast; Shanmei Wang,1 Qi Zhang,1 Youhua Yuan,1 Nan Jing,1 Jiangfeng Zhang,1 Hangchan He,3 Yi Li1 1Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China; 2Department of Clinical Microbiology, Xiayi People’s Hospital, Shangqiu, Henan, People’s Republic of China; 3Department of Clinical Laboratory, Baofeng Traditional Chinese Medicine Hospital, Pingdingshan, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Li, Department of Clinical Microbiology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan, People’s Republic of China, Tel +8615939039006, Email liyilabmed@henu.edu.cnPurpose: To analyze the risk factors and clinical outcomes of patients isolated with polymyxin B-resistant (PR) Enterobacterales from various clinical specimens to prevent and control the spread of these strains.Methods: This retrospective case-control study included 72 PR Enterobacterales-positive cases and 144 polymyxin B-susceptible (PS) Enterobacterales controls from 2018 to 2022. Patients with PR Enterobacterales isolated in various clinical cultures were defined as cases. Patients with PS Enterobacterales cultures at similar anatomic sites during the same period were randomly selected as controls. Data were collected from clinical and laboratory test records. Bivariable logistic regression and Pearson’s chi-square tests were used to assess risk factors.Results: PR strains were predominantly Klebsiella pneumoniae (72.2%) and Salmonella enteritidis (8.3%). Of the patients, 66.04% were admitted to an intensive care unit (ICU). Risk factors for isolation with PR strains included chronic heart disease (P = 0.012; odds ratio [OR] 1.15; 95% confidence interval [CI] 1.03– 1.28), immunosuppressant use (P = 0.016; OR 1.04 [1.0– 1.07), drainage tube [head] (P = 0.006; OR 1.1 [1.0– 1.1]), and polymyxin B exposure (P = 0.007; OR 1.03 [1.0– 1.06]. With respect to outcomes, admission to an ICU (P = 0.003; OR 7.1 [1.9– 25.4]), hypertension (P = 0.035; OR 1.4 [1.02– 1.83]), and drainage tube [head] (P = 0.044; OR 1.1 [1.0– 1.15]) were associated with treatment failure. Additionally, treatment failure was more frequent in patients (45.83%) than in controls (14.58%).Conclusion: The major risk factors for isolation with PR strains were chronic heart disease, exposure to immunosuppressants, use of drainage tubes, and polymyxin B exposure. The isolation of PR strains in patients was a predictor of unfavorable outcomes. These findings provide a basis for monitoring the spread of PR Enterobacterales.Keywords: polymyxin B resistance, treatment failure, Klebsiella pneumoniae, Salmonella enteritidis

Xiaofen Li,1 Jimin Wu,2 Haiyan Lan,2 Weifeng Shan,2 Qiaomin Xu,2 Xiaoli Dong,2 Gongchen Duan2 1Nursing Department, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, People’s Republic of China; 2Department of Anesthesiology, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, People’s Republic of ChinaCorrespondence: Gongchen Duan, Department of Anesthesiology, Lishui People’s Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, No. 1188, Liyang Street, Lishui, Zhejiang, 323000, People’s Republic of China, Tel/Fax +8618957093030, Email 981225178@qq.comPurpose: This study was performed to evaluate the effects of intraoperative intravenous lidocaine on postoperative delirium in elderly patients with hip fracture.Patients and methods: In total, 100 elderly patients undergoing hip fracture surgery were randomized to the lidocaine group (Group L) or saline (control) group (Group C). Before anesthetic induction, Group L received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery. Group C received normal saline, and the injection methods were consistent with those in Group L. General anesthesia was induced with propofol, sufentanil, and cis-atracurium. Anesthesia was maintained by propofol and remifentanil. The primary outcome was the incidence of postoperative delirium in the first 7 postoperative days. The secondary outcomes included the severity of delirium, onset and duration of delirium, emergence agitation, adverse events, total propofol dose, intraoperative opioid dosage, length of post-anesthesia care unit stay, extubation time, and patient satisfaction with postoperative pain management.Results: All 100 patients completed the study. The incidence of postoperative delirium was lower in Group L than in Group C (14% vs 36%, P = 0.011). The delirium severity scores were lower in Group L (3 [3– 4]) than in Group C (4 [4– 5]) (P = 0.017). In addition, the incidences of hypertension, tachycardia, and emergence agitation were significantly lower in Group L than in Group C. No cases of local anesthetic toxicity occurred in either group.Conclusion: Patients received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery, which can reduce the incidence of postoperative delirium in elderly patients undergoing hip fracture. In addition, the used regimen of lidocaine would not increase the risk of local anesthetic toxicity.Keywords: lidocaine, postoperative delirium, hip fracture, elderly patients

Jiajia Wu,1,2,&ast; Shuangyu Qi,1,2,&ast; Wei Yu,3,&ast; Yujun Gao,4 Jun Ma1,2,4 1Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 2Wuhan Hospital for Psychotherapy, Wuhan, People’s Republic of China; 3Department of Psychiatry, Xianning Bode Mental Hospital, Xianning, People’s Republic of China; 4Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ma, Department of Psychiatry, Wuhan Mental Health Center, No. 89, Gongnongbing Road, Wuhan, Hubei Province, People’s Republic of China, Email majun0313@wo.cn; Yujun Gao, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, People’s Republic of China, Email Gaoyujun19820214@163.comIntroduction: Abnormal brain networks with emotional response in bipolar disorder (BD). However, there have been few studies on the local consistency between manic episodes in drug-naive first-episode BD patients and healthy controls (HCs). The purpose of this study is to evaluate the utility of neural activity values analyzed by Regional Homogeneity (ReHo).Methods: Thirty-seven manic episodes in first-episode, drug-naive BD patients and 37 HCs participated in resting-state functional magnetic resonance rescanning and scale estimation. Reho and receiver operating characteristic (ROC) curve methods were used to analyze the imaging data. Support vector machine (SVM) method was used to analyze ReHo in different brain regions.Results: Compared to HCs, ReHo increased in the left middle temporal gyrus (MTG.L), posterior cingulate gyrus (PCG), inferior parietal gyrus, and bilateral angular gyrus, and decreased in the left dorsolateral superior frontal gyrus in target group. The ROC results showed that the ReHo value of the left PCG could discriminate the target group from the HCs, and the AUC was 0.8766. In addition, the results of the support vector machine show that the increase in ReHo value in the left PCG can effectively discriminate the patients from the controls, with accuracy, sensitivity, and specificity of 86.02%, 86.49%, and 81.08%, respectively.Conclusion: The increased activity of the left PCG may contribute new evidence of participation in the pathophysiology of manic episodes in first-episode, drug-naive BD patients. The Reho value of the left posterior cingulate gyrus may be a potential neuroimaging biomarker to discriminate target group from HCs.Keywords: bipolar disorder, first-episode, drug-naïve, manic episode, left posterior cingulate gyrus, regional homogeneity

Jiangnan Wu,1,&ast; Chao Zhang,2,&ast; Feng He,3,&ast; Yuan Wang,4 Liangnan Zeng,5 Wei Liu,6 Di Zhao,7 Jingkun Mao,1 Fei Gao8 1Department of Artificial Intelligence, Tianjin University of Technology, Tianjin, People’s Republic of China; 2Sixth Department of Oncology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, People’s Republic of China; 5Department of Nursing, Chengdu Fifth People’s Hospital, The Fifth People’s Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 6Hebei Psychological Counselor Association, Shijiazhuang, People’s Republic of China; 7Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 8Hebei General Hospital, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Zhao; Fei Gao, Tel +86-13363833833 ; +86-13933173693, Email 179381749@qq.com; 27909361@qq.comBackground: The intention to leave among intensive care unit (ICU) healthcare professionals in China has become a concerning issue. Therefore, understanding the factors influencing the intention to leave and implementing appropriate measures have become urgent needs for maintaining a stable healthcare workforce.Objective: This study aims to investigate the current status of intention to leave among ICU healthcare professionals in China, explore the relevant factors affecting this intention, and provide targeted recommendations to reduce the intention to leave among healthcare professionals.Methods: A cross-sectional survey was conducted, involving ICU healthcare professionals from 3-A hospitals of the 34 provinces in China. The survey encompassed 22 indicators, including demographic information (marital status, children, income), work-related factors (weekly working hours, night shift frequency, hospital environment), and psychological assessment (using Symptom Checklist-90 (SCL-90)). The data from a sample population of 3653 individuals were analyzed using the extreme gradient boosting (XGBoost) method to predict intention to leave.Results: The survey results revealed that 62.09% (2268 individuals) of the surveyed ICU healthcare professionals expressed an intention to leave. The XGBoost model achieved a predictive accuracy of 75.38% and an Area Under the Curve (AUC) of 0.77.Conclusion: Satisfaction with income was found to be the strongest predictor of intention to leave among ICU healthcare professionals. Additionally, factors such as years of experience, night shift frequency, and pride in hospital work were found to play significant roles in influencing the intention to leave.Keywords: ICU healthcare professionals, intention to leave, cross-sectional survey, extreme gradient boosting, XGBoost

Yu Cao,1 Ying Han,2 Jiangping Wu,1 Jianping Sun,3 Yanchao Dai,3 Guifang Qiao,3 Kang Li,3 Ang Li,3 Yonghong Zhang,4 Yingmin Ma,5,&ast; Qingkun Song1,3,&ast; 1Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Biobank, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email ma.yingmin@163.com Qingkun Song, Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email songqingkun@ccmu.edu.cnBackground: For the distinct immune/inflammatory responses from Omicron variant infection, this study aimed to investigate the diagnostic efficacy of systemic inflammatory indicators and the clinical efficacy of corticosteroids on the in-hospital mortality among COVID-19 patients.Methods: Under a retrospective cohort study, 1081 COVID-19 patients were recruited from Beijing Youan Hospital, Capital Medical University between November 16, 2022 and January 30, 2023. We chose neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), and CRP-to-albumin ratio (CAR) as the systemic inflammatory indicators. Receiver operating curve (ROC) and multivariate logistic regression analysis were used to determine the diagnostic efficacy of systemic inflammatory indicators and the association between systemic inflammatory indicators and in-hospital mortality.Results: Among 684 patients included in analysis, 96 died during hospitalization. NLR, CLR and CAR performed well (with an area under the curve (AUC) greater than 0.75) in discriminating in-hospital mortality among COVID-19 patients. The severe status of systemic inflammation, with optimal cut-off value derived from ROC analysis, significantly associated higher risk of in-hospital mortality (OR = 3.81 for NLR ≥ 6.131; OR = 3.76 for CLR ≥ 45.455; OR = 5.10 for CAR ≥ 1.436). Corticosteroids use within 72 hours of admission increased the in-hospital mortality 2.88-fold for COVID-19 patients. In the subgroup of patients with severe systemic inflammation, corticosteroids increased the risk of in-hospital mortality (OR = 2.11 for NLR, p = 0.055; OR = 2.94 for CLR, p = 0.005; OR = 2.31 for CAR, p = 0.036).Conclusion: Systemic inflammatory indicators had good diagnostic performance for in-hospital mortality. Patients with severe systemic inflammatory status should not receive corticosteroid treatment and further studies are warranted for confirmation.Keywords: COVID-19, systemic inflammatory indicators, in-hospital mortality, anti-inflammatory treatment

Jiangqin Tan,1,&ast; Wanxiang Zheng,2,&ast; Chen Xu,3 Xiaolong Qu,2 Jingxing Wu,3 Min Jiang,2 Haiyan Xu4 1Team 17, Group 5, School of Basic Medicine, Army Military Medical University, Chongqing, People’s Republic of China; 2Department of Cardiology, Southwest Hospital, Army Military Medical University, Chongqing, People’s Republic of China; 3Department of Military Psychology, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China; 4Experimental Research Center for Medical and Psychological Science, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Xu, Army Military Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email xhycq007@163.comAbstract: New approaches to medication adherence interventions are needed. This manuscript presents a highly structured protocol of a single-session solution-focused brief therapy (SFBT) for medication adherence intervention (SFBT-MAI) delivered by general providers. It conceptually integrates the procedure of tailored interventions, techniques of SFBT, and the four steps of Qitang Lin’ conceptualization of single-session SFBT. With specific techniques and examples to reduce operational difficulties, the SFBT-MAI includes two parts. The first part focuses on selecting non-adherent patients and clarifying their barriers to medication adherence. The second part focuses on individualized interventions with four steps: closing, hoping, empowering, and changing and acting. It is hoped that this work will improve the effectiveness of medication adherence interventions for patients with coronary heart disease and to promote the use of brief psychological interventions in clinical practice.Keywords: medication adherence, tailored intervention, psychological intervention, solution-focused brief therapy, general provider, coronary heart disease

Huimin Zhang,1,&ast; Chengyu Zang,1,2,&ast; Wen Zhao,1 Linfeng Zhang,1 Rui Liu,1 Zhang Feng,1 Jie Wu,1 Rongtao Cui1– 3 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exo) have been shown to have significant potential in wound healing and scar relief processes. According to reports, TNFSF13 and HSPG2 are associated with various fibrotic diseases. The aim of this study is to investigate how TNFSF13 and HSPG2 affect the formation of hypertrophic scar (HS) and the mechanism by which exosomes regulate HS.Methods: Immunohistochemistry, qRT-PCR, Western blot, and immunofluorescence were performed to measure TNFSF13 expression in HS skin tissues and hypertrophic scar fibroblast (HSF). HSF were treated with recombinant TNFSF13 protein and TNFSF13 siRNAs to probe the effect of TNFSF13 on the activity of HSF. The CCK-8, EdU, Transwell, and Western blot were used to investigate the role of TNFSF13 in viability, proliferation and inflammation. The influence of MSC-exo on the proliferation and function of HSF was determined by scratch and Western blot.Results: TNFSF13 was dramatically up-regulated in HS skin tissues and HSF. Recombinant TNFSF13 protein increased cell viability, proliferation, migration, fibrosis, inflammation, and the binding between TNFSF13 and HSPG2 of HSF. The opposite results were obtained in TNFSF13 siRNAs transferred HSF. Furthermore, TNFSF13 activated the nuclear factor-κB (NF-κB) signaling pathway. Silencing of HSPG2 and inhibition of NF-κB remarkably eliminated the promoting effects of TNFSF13 on cell viability, proliferation, migration, fibrosis and inflammation of HSF. MSC-exo reduced α-SMA and COL1A1 inhibited the proliferation and migration of HSF by inhibiting TNFSF13 and HSPG2.Conclusion: TNFSF13 activates NF-κB signaling pathway by interacting with HSPG2, which regulates the proliferation, migration, fibrosis and inflammatory response of HSF. Through the above mechanisms, knocking out TNFSF13 can inhibit the proliferation, migration, fibrosis and inflammatory response of HSF, whereas MSC-exo could reverse this process. These results suggest that MSC-exo alleviates HS by inhibiting the fibroblasts via TNFSF-13/HSPG2 signaling pathway.Keywords: TNFSF13, HSPG2, hypertrophic scar(HS), MSC-exo, fibroblasts

Jingjie Wu,1 Erxu Xue,1 Siyuan Huang,2 Yujia Fu,3 Dandan Chen,1 Jing Shao,3 Hui Zhang,4 Leiwen Tang,1 Zhihong Ye1 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Nursing Department, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3School of Nursing, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Nursing Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Zhihong Ye, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3rd of East Qingchun Road, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +8613606612119, Email 3192005@zju.edu.cnPurpose: A lack of coordinated care leads to multiple adverse effects for older adults with multimorbidity, including high treatment burdens, adverse health outcomes, reduplicated healthcare service utilization, and catastrophic healthcare expenditure. To foster healthy aging, person-centered integrated care that is responsive to older adults has been proposed by the World Health Organization. The objective of this study was to identify factors that impact the successful implementation of integrated care for older adults with multimorbidity in China.Patients and Methods: From July 2022 to May 2023, 33 healthcare providers and managers involved in the delivery and management of healthcare services for older adults with multimorbidity were recruited from Zhejiang Province, China using purposeful and maximum variation sampling methods. Semi-structured, face-to-face in-depth interviews were conducted by the same interviewer in the participants’ native Chinese language until data saturation was reached. Inductive thematic analysis was used to analyze the data, and then, themes were mapped onto six dimensions using the Rainbow Model of Integrated Care to allow for a comprehensive view of the study’s findings.Results: Eleven themes were generated as facilitators and barriers to integrated care for older adults with multimorbidity in China. These themes include (1) clinical integration: patient-centered care, (2) professional integration: interdisciplinary teams and training, (3) organizational integration: resources and accessibility, (4) system integration: community and funds, incentives, and health insurance, (5) functional integration: electronic health record systems, workforce, and guidelines, and (6) normative integration: shared mission.Conclusion: Guided by the Rainbow Model of Integrated Care, various factors at both micro, meso, and macro levels that impact the implementation of integrated care for older adults with multimorbidity in the Chinese context have been identified in this study. The strategies for future interventions and policies should focus on promoting facilitators and addressing barriers.Keywords: delivery of health care, integrated, aged, older adult, multiple chronic conditions, facilitator, barrier

Jingmei Li,1,&ast; Jin Zhang,1,&ast; Yan Gao,1 Sibei Lei,1 Jieping Wu,1 Xiaohua Chen,1 Kaiyu Wang,1 Xingmei Duan,2 Ke Men1 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comIntroduction: Cell-membrane nanocarriers are usually constructed by modifying the nanoparticle surface with cell membrane extracts, which has a direct benefit in endowing targeting capacity to nanocarriers based on their original cell types. However, delivering nucleic acid cargos by cell membrane–based nanoparticles is difficult owing to the strong negative charge of the cell membrane fraction. In this study, we developed a cancer cell membrane–based drug delivery system, the cMDS, for efficient siRNA delivery. Meanwhile, the cancer-specific immune response stimulated by the gene vector itself could offer synergistic anti-cancer ability.Methods: The cMDS was prepared by ultrasound, and its transfection efficiency and anti-cancer ability were examined using cultures of CT26 cells. MTT and red blood cell hemolysis tests were performed to assess the safety of cMDS, while its targeted gene delivery and strong immune stimulation were investigated in a subcutaneous tumor model. Moreover, the detailed anti-cancer immune stimulation mechanisms of cMDS are uncovered by protein chip analysis.Results: The cMDS was spherical core-shell structure. It showed high transfection efficiency and anti-cancer ability in vitro. In animal experiments, intravenously administered cMDS/siStat3 complex efficiently suppress the growth of colon cancer. Moreover, the result of protein chip analysis suggested that cMDS affect the migration and chemotaxis of immune cells.Conclusion: The cMDS shows obvious tumor tissue-specific accumulation properties and strong immune stimulation ability. It is an advanced targeted gene delivery system with potent immunotherapeutic properties.Keywords: bioinspired material, cancer cell membrane, targeted siRNA delivery, immunotherapeutic, colon cancer

Yongkang Xu, Shumin Fu, Kan Liu, Ye Mao, Jianbing Wu Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Jianbing Wu, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Email hhgwjb@163.comPurpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure.Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models.Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥ 400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis.Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.Keywords: hepatocellular carcinoma, lenvatinib, PD-1 inhibitors, regorafenib, sorafenib, overall survival

Rongdi Xu,1,2 Cheng Wang,1,2 Jiachun Lang,1,2 Jikun Wu,1,2 Yuecheng Hu,2 Tong Wang,1,2 Jingxia Zhang,2 Hongliang Cong,1– 3 Le Wang2,3 1Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Cardiology, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of Cardiovascular Emergency and Critical Care, Tianjin Municipal Science and Technology Bureau, Tianjin Chest Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Hongliang Cong; Le Wang, Department of Cardiology, Tianjin Chest Hospital, 261 Tai’erzhuang Road, Jinnan District, Tianjin, 300222, People’s Republic of China, Tel +86-22-88185003, Email hongliangcong@126.com; 2003615300@163.comPurpose: The incidence of prediabetes mellitus (pre-DM) is increasing among young individuals. Whether pre-DM can predict adverse cardiovascular events in acute coronary syndrome (ACS) patients remains controversial. This study aimed to investigate the impact of pre-DM on the long-term clinical outcomes of patients aged≤ 45 years with new-onset ACS.Patients and methods: A total of 1113 patients with new-onset ACS (aged≤ 45 years) who underwent percutaneous coronary intervention (PCI) were enrolled in this study. Patients were divided into three groups according to their glycemic status or history: normal glucose metabolism (NGM), prediabetes (pre-DM), and diabetes mellitus (DM). The primary endpoint was defined as a composite of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI), stroke, or unplanned repeat revascularization. Multivariate Cox regression analysis was performed to explore the association between abnormal glycemic status and MACE.Results: The prevalence of NGM, pre-DM, and DM were 45.9% (n=511), 27.0% (n=301), and 27.0% (n=301), respectively. During a median follow-up of 65 months, MACE occurred in 23.5% (n=120) of NGM, 29.2% (n=88) of pre-DM, and 34.6% (n=104) of DM (P=0.003). After multivariate adjustment, both pre-DM and DM significantly increased the risk of MACE compared with the NGM group (pre-DM: HR1.38, CI95% 1.05– 1.83, P=0.023; DM: HR1.65, CI95% 1.27– 2.16, P< 0.001). Moreover, pre-DM had a similar impact on MACE as DM in young patients with ACS (P=0.162).Conclusion: Pre-DM was common among patients aged≤ 45 years with new-onset ACS. Pre-DM was associated with an increased risk of future MACE compared to NGM.Keywords: young patients, prediabetes, acute coronary syndrome

Jingjie Wu,1,&ast; Hui Zhang,2,&ast; Jing Shao,3 Dandan Chen,1 Erxu Xue,1 Siyuan Huang,4 Yujia Fu,3 Leiwen Tang,1 Zhihong Ye1 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Nursing Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 3Nursing Faculty, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Nursing Department, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Ye, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3th of East Qingchun Road, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +8613606612119, Email 3192005@zju.edu.cnPurpose: To summarize adverse healthcare outcomes experienced by older adults with multimorbidity and barriers perceived by stakeholders regarding the healthcare systems primarily designed to address individual health conditions. Healthcare elements that aim to provide coordinated, continuous, and comprehensive services for this population were also identified.Patients and Methods: We applied the methodology framework developed by Arksey and O’Malley to guide the review. The three-step search strategy was used to identify relevant English reviews that focused on adverse healthcare outcomes and barriers encountered by older adults with multimorbidity and other stakeholders regarding the single-disease-focused healthcare systems, as well as those concentrated on healthcare elements that aim to provide coordinated, continuous, and comprehensive services for older adults with multimorbidity. Five electronic databases, including PubMed/Medline, CINAHL, Web of Science Core Collection, Cochrane Library, and Embase, were systematically searched from database inception to February 2022. A standardized table was used to extract data. Thematic analysis was then conducted under the guidance of the Rainbow Model of Integrated Care and the Chronic Care Model.Results: Twenty reviews were included in this study. Therapeutic competitions, high healthcare service utilization, and high healthcare costs were three adverse healthcare outcomes experienced by patients. Both patients and healthcare professionals faced various barriers. Other stakeholders, including informal caregivers, healthcare managers, and policymakers, also perceived several barriers. Numerous healthcare elements were identified that may contribute to optimized services. The elements most frequently mentioned included the implementation of shared decision-making, comprehensive geriatric assessments, and individual care plans.Conclusion: This study conducted a comprehensive overview of the current knowledge related to healthcare for older adults with multimorbidity. In the future, it is necessary to develop more coordinated, continuous, and comprehensive healthcare service delivery models based on the healthcare needs of older adults with multimorbidity and the specific characteristics of different countries.Keywords: multiple chronic conditions, aging, healthcare service delivery, long-term care, review

Daniel KY Zheng,1 Gregory N Kawchuk,2 André E Bussières,3,4 Fadi M Al Zoubi,1 Jan Hartvigsen,5 Siu Ngor Fu,1 Katie de Luca,6 Debra K Weiner,7,8 Jaro Karppinen,9,10 Dino Samartzis,11 Manuela L Ferreira,12 Jinlong Wu,13 Liz Dennett,2 Arnold YL Wong1 1Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, People’s Republic of China; 2University of Alberta, Edmonton, Canada; 3Université McGill, Montreal, Canada; 4Université du Québec à Trois-Rivières, Trois‑Rivières, Canada; 5University of Southern Denmark, Odense, Denmark; 6Central Queensland University, Brisbane, Australia; 7University of Pittsburgh, Pittsburgh, PA, USA; 8VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; 9Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland; 10Rehabilitation Services of South Karelia Social and Health Care District, Lappeenranta, Finland; 11Rush University Medical Center, Chicago, IL, USA; 12The University of Sydney, Sydney, Australia; 13Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Arnold YL Wong, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, People’s Republic of China, Tel +852 2766 6741, Email arnold.wong@polyu.edu.hkAbstract: Although the number of publications focusing on low back pain in older adults (LBP-O) and working-age adults (LBP-W) has been growing for decades, comparative research trends in these two populations, which may help to guide future investigation, have not been rigorously explored. This analysis aimed to describe publication patterns and trends of research targeting LBP-O and LBP-W over the last three decades. Peer-reviewed LBP-O and LBP-W articles published between 1993 and 2023 were retrieved from the Web of Science, which provided the details of annual publication volume, and prominent journals/countries/institutions. The relationship between the annual publication volumes and years was analyzed by Spearman correlation analysis. The hot topics and emerging trends were analyzed by VOSviewer and CiteSpace, respectively. A total of 4217 LBP-O-related and 50,559 LBP-W-related documents were included. The annual publication volumes of LBP-O and LBP-W articles increased over the years (r=0.995 to 0.998, p< 0.001). The United States had the highest number of prominent institutions publishing relevant articles. The most prolific journal for LBP-O (5.4%) and LBP-W-related (6.1%) papers is the journal “Spine”. Cognitive behavioral therapy, intervertebral disc (IVD) degeneration, physiotherapy, physical activity, and walking were the recent hot topics and physical activity was an emerging trend in LBP-O, while surgery and IVD degeneration (also a hot topic) were emerging trends in LBP-W. This study highlights the paucity of LBP-O-related research in the past. The United States and the journal Spine stand out in LBP research. The research trend of physical activity in LBP-O is consistent with the recognized importance of physical activity for older adults in general, and for managing LBP-O in particular. Conversely, the emerging trends of surgery and intervertebral disc degeneration in LBP-W research highlight a focus on the biomedical model of LBP despite LBP being a biopsychosocial condition.Keywords: low back pain, older adults, working-age adults, bibliometrics, intervertebral disc degeneration, physical activity, surgery

Yifan Qin, Huiyu She, Wenrui Peng, Xiaofeng Zhou, Yiting Wang, Peng Jiang, Jin Wu Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Jin Wu, Department of Anesthesiology, Affiliated Hospital of Jiangsu University, 438 Jie Fang Road, Zhenjiang, Jiangsu, 212001, People’s Republic of China, Email wujin914@hotmail.comPurpose: Multiple regional nerve blocks proved no additional benefit in total laparoscopic hysterectomy in multimodal analgesia, as postoperative pain may mainly originate from the vaginal cuff. Theoretically, caudal block can relieve pain from the vaginal cuff by a sacral spinal nerve block. We aimed to verify whether a caudal block with ropivacaine and morphine can achieve an analgesic effect without additional adverse effects after a total laparoscopic hysterectomy.Patients and Methods: Forty-eight patients undergoing total laparoscopic hysterectomy were randomly allocated to receive preoperative caudal block with 20 mL of mixture including 0.25% ropivacaine and 2 mg morphine (caudal block group) or sham block (sham group). The primary outcome was the postoperative 24 h cumulative sufentanil consumption.Results: Median (IQR) sufentanil consumption in the first 24 postoperative hours of the caudal block group and the sham group was 0.00 (0.00 to 0.05) μg/kg vs 0.13 (0.04 to 0.21) μg/kg, respectively, p < 0.001. The majority of patients felt that visceral pain was more intense than incisional pain at 1, 6, 12, and 24 h post-surgery in the sham group (95.8% at 1 h, 95.8% at 6 h, 95.8% at 12 h, and 75% at 24 h post-surgery). Compared to the sham group, the caudal block reduced visceral pain scores at rest and during movement at 1 h (p < 0.001), 6 h (p < 0.001), 12 h (p < 0.001), and 24 h (p < 0.001) post-surgery. Intraoperative remifentanil consumption was significantly lower in the caudal block group than in the sham group (p = 0.004). There were no significant differences in other secondary outcomes between the two groups.Conclusion: A caudal block with ropivacaine and morphine could provide a satisfactory analgesic effect for 24 h postoperatively without additional adverse effects after total laparoscopic hysterectomy.Keywords: anesthesia, caudal, visceral pain, hysterectomy, pain, postoperative, postoperative nausea and vomiting, gynecologic surgical procedures

Lantian Wang,1,2 Xiawei Li,1,2 Jian Wu,1,2 Qiang Tang1,2 1Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lantian Wang, Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China, Email wanglantian@zju.edu.cnBackground: Cancers trigger systemic metabolic disorders usually associated with glucose intolerance, which is an initially apparent phenomenon. One of the features of pancreatic cancer (PC) metabolic reprogramming is the crosstalk between PC and peripheral tissues (skeletal muscle and adipose tissues), emphasized by insulin resistance (IR). Our previous study reported that mice pancreatic cancer-derived exosomes could induce skeletal muscle cells (C2C12) IR, and exosomal microRNAs (miRNAs) may exert an important effect. However, the underlying mechanism remains to be further elucidated.Methods: qPCR was used to determine the expression of let-7b-5p in normal pancreatic islet cells and PC cells. Exosomes were purified from PC cell culture medium by ultracentrifugation. The role let-7b-5p on IR-mediated by PC cells-derived exosomes was asses by Oil Red O staining using miRNA inhibitor. Western blot assay was performed to examine the expression of IR-related genes and the activation of signaling pathways. A Luciferase experiment was applied to confirm how let-7b-5p regulated the expression of RNF20. IP/WB analysis further determined whether RNF20 promoted STAT3 ubiquitination. Rescue experiment using RNF20 overexpression plasmid was performed to confirm the role of RNF20 on IR-mediated using PC cell-derived exosomes in C2C12 myotube cells.Results: miRNA-let-7b-5p was identified as the key exosomal miRNA, which could promote the IR in C2C12 myotube cells supported the lipid accumulation, the activation of STAT3/FOXO1 axis, and the decreased expression of IRS-1 and GLUT4. RNF20, an E3 ubiquitin ligase, was confirmed as the target gene of let-7b-5p and was found to improve IR by downregulating STAT3 protein expression via ubiquitination-mediated protein degradation. The ectopic expression of RNF20 could effectively attenuate the IR mediated by the pancreatic cancer-derived exosomes in C2C12 myotube cells.Conclusion: Our data suggest that exosomal miRNA-let-7b-5p may promote IR in C2C12 myotube cells by targeting RNF20 to activate the STAT3/FOXO1 axis.Graphical Abstract: Keywords: insulin resistance, exosome, let-7b-5p, RNF20, STAT3, FOXO1

Jiahui Wu,1,2 Huidan Luo,1,2 Kun Wang,1,2 Bin Yi1,2 1Department of Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Bin Yi, Department of Clinical Laboratory and Medical Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-13707495781, Fax +86-73189753200, Email xyyibin@163.comPurpose: The mortality rate of nasopharyngeal carcinoma (NPC) remains high due to the absence of quick and accurate diagnostic approaches at its early stage. Our aim is to evaluate the diagnostic value of the elevated expression of Aurora kinase A (AURKA) and the oxidative stress markers (such as glutathione, superoxide dismutase and malondialdehyde) in serum of NPC patients and to establish a nomogram model for predicting NPC on the ground of these biomarkers.Patients and Methods: Serum samples from 93 NPC patients and 94 healthy subjects were collected. Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the AURKA level, while oxidative stress markers were measured by commercially available appropriate kits. Logistic regression was used for NPC predictor identification and nomogram construction. The training and validation cohorts (3:1) were randomly split up from the participants. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCAs) were performed to validate the nomogram.Results: AURKA and malondialdehyde (MDA) levels were significantly high in the NPC population compared to the healthy controls (P < 0.0001). The nomogram resulted in an area under the curve (AUC) of 0.897 (95% confidence interval: 0.848– 0.947) in the training set and AUC of 0.770 (0.628– 0.912) in the validation set. The predicted probability and the actual probability matched well in the nomogram (P > 0.05). DCAs showed good results too.Conclusion: Serum levels of AURKA, SOD, and MDA have diagnostic values in NPC. The nomogram based on the identified biomarkers is favorable for NPC prediction.Keywords: nasopharyngeal carcinoma, AURKA, SOD, MDA, nomogram

Shanlian Hu,1 Depei Wu,2 Jing Wu,3 Yabing Zhang,4 Mette Bøgelund,5 Johannes Pöhlmann,6 Richard F Pollock6 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2First Affiliated Hospital of Soochow University, Soochow University, Suzhou, People’s Republic of China; 3School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 4Shanghai Institute of Technology, Shanghai, People’s Republic of China; 5Incentive Partners ApS, Holte, Denmark; 6Covalence Research Ltd, Harpenden, United KingdomCorrespondence: Richard F Pollock, Covalence Research Ltd, Rivers Lodge, West Common, Harpenden, AL5 2JD, United Kingdom, Tel +44 20 8638 6525, Email pollock@covalence-research.comPurpose: Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions.Methods: An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model.Results: The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15– 30 minutes or 30– 60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values < 0.01).Conclusion: This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients’ quality of life.Plain Language Summary: A lack of iron in the body can be treated successfully using intravenous infusions of iron, but it is not yet known how different intravenous iron formulations affect patients’ quality of life.Intravenous iron formulations differ in how often and for how long (per infusion) they need to be administered; for example, while one available intravenous iron formulation allows most iron deficits to be corrected in a single visit, others can require several visits. Formulations also seem to differ in the risk of complications relating to low phosphate and bone softening.This study presented descriptions of treatment options, differing in the number and duration of infusions as well as in risk, to more than 1000 Chinese respondents. Based on their answers, the differences between intravenous iron administration regimes could be valued and linked to quality of life. Intravenous iron treatment with fewer, shorter infusions and without risk of bone softening was found to come with a better quality of life. Each additional infusion reduced quality of life, but less so if treatment already involved several infusions. These findings can help patients and physicians to make clinical decisions that focus not only on efficacy and safety but also on the quality of life.Keywords: China, disutility, health-related quality of life, intravenous iron, iron deficiency, time trade-off

Yue Wang,1,2 Jun Li,3 Jianming Wu,3 Shihong Gu,3 Huishu Hu,3 Rongjuan Cai,2 Man Wang,4 Yue Zou3 1Institute of Shanghai Oriental Beauty Valley, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 2School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, People’s Republic of China; 3R&D Center, JALA (Group) Co., Ltd, Shanghai, People’s Republic of China; 4Department of Nutrition, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, People’s Republic of ChinaCorrespondence: Yue Zou, R&D Center, JALA (Group) Co., Ltd, Building 2, No. 333, Guiping Road, Xuhui District, Shanghai, 200233, People’s Republic of China, Email zouyue3@jala.com.cnIntroduction: Sensitive scalp is one of the most frequent complaints related to sensitive skin syndrome, characterized by unpleasant sensory reactions in the absence of visible signs of inflammation. In this study, the effects of topical application of postbiotic Himalaya-derived Saccharomyces and Lactobacillus ferment complex (SLFC) on the bacterial and fungal scalp microbiome at the taxonomic level and alleviation of sensitive skin syndrome were investigated.Methods: Firstly, healthy female participants (aged 30– 45) were classified into a healthy scalp group and a sensitive scalp group based on the questionnaire. Thereafter, topical application of SLFC on sensitive scalp as well as scalp microbiome was evaluated, with the difference in the distribution of microbial taxa between healthy and sensitive scalp communities was assessed using 16S rRNA and ITS1 sequencing analysis. In addition, the effect of SLFC on scalp microbiome at the species level for Cutibacterium acnes, Staphylococcus epidermidis, and Malassezia restricta was evaluated by the qPCR assessment.Results: After treatment with SLFC for 28 days, the abundance of Staphylococcus, Lawsonella, and Fusarium in the sensitive scalp group was highly significantly increased (p < 0.001), while the abundance of Cutibacterium and Malassezia was highly significantly decreased (p < 0.001). Furthermore, the self-assessment questionnaire indicated a syndrome alleviation effect of 100% after 28 days with a twice-daily application of the SLFC.Discussion: The obtained results would help to better understand the microbial community of the sensitive scalp and provide useful information on utilization of SLFC for maintaining a healthy scalp and modulating the scalp microbiome.Keywords: sensitive scalp, scalp microbiome, postbiotics, microbial diversity, questionnaire analysis

Xiaofeng Zhang,1,&ast; Jiaqi Zhang,1,&ast; Yongzhi Cai,1 Yue Li,1 Shiyun Qin,1 Jingtao Li,1 Decai Zeng,1 Tongtong Huang,1 Liu Liu Huang,2 Yanfen Zhong,1 Lihui Wei,1 Ji Wu1 1Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Email gxnnwuji@163.comBackground: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR.Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a> 15% increase in left ventricular end-diastolic volume or > 10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling.Results: The variables associated with adverse LVR in this study were LVGLS (P< 0.001, odds ratio: 1.996, 95% CI: 1.394– 2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007– 1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of − 15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88).Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.Keywords: rheumatic mitral stenosis, left ventricular remodeling, left ventricular global longitudinal strain, mechanical dispersion, speckle tracking echocardiography

Jiaxin Yu,1,2 Wei Zuo,1,2 Hongwei Fan,1,3 Jiayu Wu,1,2 Luyao Qiao,1,2,4 Benyu Yang,1,2,5 Wenxi Li,1,2,5 Yang Yang,1,2,&ast; Bo Zhang1,2,&ast; 1Department of Pharmacy, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Infectious Medicine, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yang; Bo Zhang, Department of pharmacy, Peking Union Medical College Hospital, Dongdan Campus, No. 1 Shuaifuyuan Wangfujing Dongcheng, District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69156527, Email yangyangsdu2010@126.com; zhangbopumch@163.comPurpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT).Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively.Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (> 3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (< 3.75 g/d, p = 0.03).Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage > 3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.Keywords: ceftazidime-avibactam, renal replacement therapy, infections, intensive care unit, carbapenem-resistant gram-negative bacteria

Xia Yu,1,&ast; Yingxia He,2,&ast; Yuzhen Gu,1,&ast; Tingting Zhang,1 Fengmin Huo,1 Qian Liang,1 Jing Wu,1 Yan Hu,2 Xuan Wang,2 Wei Tang,2 Hairong Huang,1 Guan Liu2 1National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Wuhan Pulmonary Hospital, Wuhan Institution of Tuberculosis Control, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hairong Huang; Guan Liu, Email huanghairong@tb123.com; liuguantbdoctor@hotmail.comObjective: To evaluate the resolution of chromosomal virulence D (chvD) as a novel marker for mycobacterial species identification.Methods: A segment of chvD (652 bp) was amplified by PCR from 63 mycobacterial reference strains, 163 nontuberculous mycobacterial clinical isolates, and 16 M. tuberculosis complex (MTBC) clinical isolates. A phylogenetic tree based on the reference strains was constructed by the neighbor-joining and IQ-tree methods. Comparative sequence analysis of the homologous chvD gene efficiently differentiated the species within the genus Mycobacterium. Slowly growing Mycobacterium (SGM) and rapidly growing Mycobacterium (RGM) were separated in the phylogenetic tree based on the chvD gene.Results: The sequence discrepancies were obvious between M. kansasii and M. gastri, M. chelonae and M. abscessus, and M. avium and M. intracellulare, none of which could be achieved by 16S ribosomal RNA (rRNA) homologous gene alignment. Furthermore, chvD manifested larger intraspecies diversity among members of M. intracellulare subspecies. A total of 174 of the 179 (97.21%) clinical isolates, consisting of 12 mycobacterial species, were identified correctly by chvD blast. Four M. abscessus subsp. abscessus were identified as M. abscessus subsp. bolletii by chvD. MTBC isolates were indistinguishable, because they showed 99.84%– 100% homology.Conclusion: Homologous chvD is a promising gene marker for identifying mycobacterial species, and could be used for highly accurate species identification among mycobacteria.Keywords: species identification, Mycobacterium, chromosomal virulence D, phylogenetic tree

Jie Wu,1,2 Guangcun Zhang,3 Qiang Zhao,3 Lifeng Wang,3 Jiyong Yang,3 Junchang Cui1 1Department of Respiratory Diseases, The Eighth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 3Laboratory Medicine Department, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Junchang Cui, The Eighth Medical Center, Department of Respiratory Diseases, Chinese People’s Liberation Army General Hospital, No. 17 Heishanhu Road, Haidian District, Beijing, 100091, People’s Republic of China, Tel +86 010 6677 5010, Email guoguoyoumeng@163.comPurpose: To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Stenotrophomonas maltophilia and evaluated their dosing regimens.Methods: Seventy-seven unique strains of S. maltophilia were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC).Results: Eravacycline had excellent in vitro antibacterial activity against LVFX-non-susceptible and/or TMP-SMZ-resistant S. maltophilia. Monte Carlo simulations showed that for LVFX-non-susceptible strains, the cumulative fraction of response (CFR) of minocycline at the conventional recommended dose of 100 mg q12 h was 90.90%; for TMP-SMZ-resistant strains, the CFR of minocycline at a high dose of 200 mg q12 h was only 91.64%. For strains resistant to both LVFX and TMP-SMZ, the CFR of minocycline at a high dose of 200 mg q12 h was 89.81%. In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h.Conclusion: For pneumonia, minocycline is better for S. maltophilia that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.Keywords: eravacycline, tetracyclines, levofloxacin, trimethoprim, sulfamethoxazole drug combination, Stenotrophomonas maltophilia, Monte Carlo method

Dongsheng Hong,1,2 Duo Lv,1 Jiaying Wu,1 Xin Li,1 Qingwei Zhao,1 Xiaoyang Lu,1 Lu Li2 1Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiaoyang Lu, Key Laboratory for Drug Evaluation and Clinical Research of Zhejiang Province, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email luxiaoyang@zju.edu.cn Lu Li, Department of Social Medicine of school of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email lilu@zju.edu.cnBackground: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients.Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department.Results: A total of 34,276 elderly hypertensive patients’ daily full medical orders were obtained. The immediate level change of drug costs after intervention was − 23.884 RMB/month (P = 0.652), and the trend change was statistically significant (− 15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was − 78.860% (95% CI: − 86.087% to − 69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed.Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.Keywords: diagnosis-intervention packet policy, daily drug cost, interrupted time series analysis, elderly hypertension, medication structure

Wanshan Zhu, Lexia Wu, Jiaming Wu, Sihong Lin, Cantu Fang, Huatang Zhang Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Huatang Zhang, Email paul201503@163.comAbstract: Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient’s prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as “pseudoprogression” during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.Keywords: small cell lung cancer, immunotherapy, pseudoprogression