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Kai Wang,1,2,&ast; Qin Gao,3,&ast; Yelong Bai,1 Rong Yu,1 Qing Luo1 1Department of Otorhinolaryngology, FirstAffiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Otorhinolaryngology, the 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, Jiangxi, People’s Republic of China; 3Department of Otorhinolaryngology, Central Theater Command General Hospital of the People’s Liberation Army of China, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Luo; Rong Yu, Department of Otorhinolaryngology, FirstAffiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86-18170846190, Email luoq@ncu.edu.cn; yurong1982@ncu.eud.cnObjective: To study the role of transforming growth factor beta 1 (TGF-β 1) and tumor necrosis factor receptor related factor 6 (TRAF6) in the progression of epithelial mesenchymal transformation (EMT) in allergic rhinitis (AR).Methods: A total of 30 patients underwent nasal endoscopic surgery at our Hospital were selected for 15 patients in each group based on their allergy status. Inferior turbinate mucosa tissue was obtained and analyzed using immunohistochemical (IHC) tests, real-time quantitative PCR (qRT-PCR) detection, and Western blotting (WB) tests to measure TGF-β 1, TRAF6, E-cadherin, Vimentin, and α-Smooth Muscle Actin (α-SMA) expression levels.Results: The expression levels of TGF-β 1, TRAF6, Vimentin, and α-SMA were significantly higher in the AR group compared to the control group as shown by IHC, qRT-PCR, and WB (P < 0.05). E-cadherin expression was significantly lower group than in the control group (P < 0.05). Protein expression of TGF-β 1 showed significantly positive correlations with TRAF6 (r = 0.8188, P = 0.0002), α-SMA (r = 0.8076, P = 0.0003), and Vimentin (r = 0.6917, P = 0.0043). There was a significantly negative correlation between protein expression of TGF-β 1 and E-cadherin (r = − 0.8032, P = 0.0003). Protein expression of TRAF6 showed a significantly negative correlation with E-cadherin (r = − 0.6405, P = 0.0101) but positive correlations with α-SMA (r = 0.5809, P = 0.0231) and Vimentin (r = 0.555, P = 0.0318).Conclusion: TGF-β 1, TRAF6, and EMT-related markers (Vimentin, α-SMA) were highly expressed in the nasal mucosa of AR patients. TGF-β 1 and TRAF6 may be involved in the epithelial-mesenchymal transition in allergic rhinitis.Keywords: allergic rhinitis, transforming growth factor β 1, tumor necrosis factor receptor associated factor 6, epithelial-mesenchymal transition, immunohistochemical

Lijuan Chen,1,&ast; Mingbo Liu,2,&ast; Yunjuan Wang,3,4,&ast; Wei Wei,1 Yaqiong Li,5 Yan Bai,1 Xuan Yu,1 Lei Jiao,6 Meiyun Wang1,4 1Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Radiotherapy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 3School of Life Sciences, Henan University, North Section of Jinming Avenue, Kaifeng, Henan, 475004, People’s Republic of China; 4Institute of Biomedicine, Henan Academy of Sciences, Zhengzhou, Henan, 450046, People’s Republic of China; 5Department of Pharmacy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 6Institute of Molecular Metrology, College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiyun Wang, The Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, No. 7, WeiWu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email mywang@zzu.edu.cnPurpose: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.Keywords: radiotherapy, glioblastoma, MnO2/Pt@BSA nanoplatform, nanocatalysis

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

Xiong Zhang,1 Min Zhou,1 Xiaorong Jin,1 Yimei Zhang,1 Wei Wei,2 Yangjuan Bai,3 Fang Ma1 1Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Digestive Surgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, 295&num;, Xichang Road, Kunming, 650032, Provence Yunnan, People’s Republic of China, Email rebeccamalei@126.comBackground: : Family coping, as an essential part of family management of patients with chronic heart failure (CHF), is an important component of CHF interventions, affecting the health of patients, family members, and the whole family. It is necessary to understand the current situation of family coping in patients with CHF to facilitate the development of family interventions for patients with CHF. This study aims to develop and validate a tool for assessing the family coping scale for patients with CHF.Methods: The semi-structured interviews, expert consensus meetings, expert consultations, and item analysis were used to develop the initial scale. We employed classical test theory and exploratory factor analysis to scrutinize and refine the items in the scale. To validate the scale, we used confirmatory factor analysis to assess structural validity. We assessed internal consistency, and split-half reliability to ensure the scale’s robustness and accuracy.Results: The FCS-CHF consisted of 24 items, including six dimensions: strategies for better management of CHF, psychological coping, substantial support by family members, emergency coping, overall heart failure awareness, and patients’ health behavior. The results of confirmatory factor analysis showed that the scale fitted the data with well construct validity. The results of the confirmatory factor analysis for the overall goodness of fit indices for the fitted model were found to be acceptable for the scale. The scale demonstrates good reliability and validity, meeting the requirements of psychometrics.Conclusions: The FCS-CHF developed in this study is considered reliable and valid, which can measure family coping in patients with CHF and provide a basis for developing family coping enhancement strategies.Keywords: chronic heart failure, family coping, scale development, reliability, validity

Zhengjiang Wang,1,2,&ast; Jiaqi Xu,1,2,&ast; Liqun Mo,1 Renshu Zhan,1,2 Jin Zhang,3 Li Liu,1,2 Jun Jiang,4 Yingying Zhang,1,2 Yiping Bai1,2 1Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA; 4Department of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingying Zhang; Yiping Bai, Email yingyingzhang917@gmail.com; baiyiping0608@163.comAbstract: Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Numerous studies have shown that irisin plays a significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, and providing neuroprotection. Additionally, irisin can exert immunomodulatory functions by regulating regulatory T cells (Tregs). Tregs are a highly differentiated subset of mature T cells that play a key role in maintaining self-immune homeostasis and are closely related to infections, inflammation, immune-related diseases, and tumors. Irisin exerts persistent positive effects on Treg cell functions through various mechanisms, including regulating Treg cell differentiation and proliferation, improving their function, modulating the balance of immune cells, increasing the production of anti-inflammatory cytokines, and enhancing metabolic functions, thereby helping to maintain immune homeostasis and prevent immune-related diseases. As an important myokine, irisin interacts with receptors on the cell membrane, activating multiple intracellular signaling pathways to regulate cell metabolism, proliferation, and function. Although the specific receptor for irisin has not been fully identified, integrins are considered potential receptors. Irisin activates various signaling pathways, including AMPK, MAPK, and PI3K/Akt, through integrin receptors, thereby exerting multiple biological effects. These research findings provide important clues for understanding the mechanisms of irisin’s action and theoretical basis for its potential applications in metabolic diseases and immunomodulation. This article reviews the relationship between irisin and Tregs, as well as the research progress of irisin in immune-related diseases such as multiple sclerosis, myasthenia gravis, acquired immune deficiency syndrome, type 1 diabetes, sepsis, and rheumatoid arthritis. Studies have revealed that irisin plays an important role in immune regulation by improving the function of Tregs, suggesting its potential application value in the treatment of immune-related diseases.Keywords: irisin, FNDC5, regulatory T cell, immunity, immune-related diseases

Honggang Guo,1,&ast; Yabin Cui,2,&ast; Yanliang Bai,1 Fan Yan,1 Wenhui Zhang,1 Yuqing Chen,1,&ast; Mingyue Shi1,&ast; 1Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Hematology, Henan University People’s Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuqing Chen; Mingyue Shi, Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, &num;7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86-18697321863 ; +86-17839931733, Email henanblood@sina.com; shimingyue16@gmail.comBackground: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined.Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs.Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis.Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.Keywords: Relapsed/refractory, acute myeloid leukemia, circular RNAs, biomarkers, prognosis

Yongfeng Lao,1,2 Yanan Bai,1,2 Xin Guan,1,2 Jian Wang,1,2 Yanan Wang,1,2 Rongxin Li,1,2 Yongqiang Ding,1,2 Zhilong Dong1,2 1Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Zhilong Dong, Department of Urology, The Second Hospital of Lanzhou University, No. 82, Cuiyingmen, Chengguan District, Lanzhou, Gansu, People’s Republic of China, Email dzl1997.student@sina.comIntroduction: Although sertraline has been widely used for chronic prostatitis (CP), the mechanisms are unclear. Herein, we explored the mechanisms of sertraline in treating CP.Methods: Network pharmacology methods were used to explore the potential targets and molecular mechanisms. LPS was used to stimulate RWPE-1 cells to construct an in vitro model of CP. An experimental autoimmune prostatitis (EAP) mice model was built. CCK-8 assay, EdU assay, BrdU detection, and Tunel assay were performed to evaluate the proliferation and apoptosis process of cells or tissues, respectively. DCFH-DA and Fluo-4 fluorescence probes were used to detect intracellular ROS and calcium concentrations. Von Frey filaments and open-field tests were utilized to evaluate pain response and depressive-like behavior of mice. Histopathology was evaluated through hematoxylin and eosin staining. RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry were utilized to evaluate the transcription, expression, and location of related proteins. Molecular dynamics (MD) simulation and surface plasmon resonance (SPR) assay were performed to measure the binding capacity of sertraline and related proteins.Results: Through a network pharmacology analysis, 27 potential targets of sertraline for CP were obtained, and 5 key targets (CHRM1, ADRA1B, HTR2B, HTR2A, and TRPV1) were finally identified. Functional experiments suggested that TRPV1 was involved in the proliferation, apoptosis inhibition, and ROS production of LPS-induced RWPE-1 cells. In vitro experiments showed that sertraline significantly inhibited cell proliferation, ROS generation, and transcription of inflammation cytokines of LPS-induced RWPE-1 cells. Additionally, sertraline markedly promoted the apoptosis level of LPS-stimulated RWPE-1 cells and elevated the expression level of BAX while reducing the expression levels of Bcl2 and Caspase-3. MD simulation and SPR assay confirmed the direct binding of sertraline to TRPV1. Moreover, sertraline significantly down-regulated the expression level of TRPV1 and inhibited calcium influx of LPS-induced RWPE-1 cells. TRPV1 agonist (Capsaicin) significantly restored the effects on proliferation, apoptosis, ROS production, and calcium influx of sertraline on LPS-induced RWPE-1 cells. Mice experiments demonstrated that sertraline treatment could reduce pain response, improve depression-like symptoms, and relieve local prostate inflammation of EAP mice, as well as down-regulated the expression level of TRPV1, inhibit the proliferation, and promote apoptosis of prostate tissues in EAP mice.Discussion: The results revealed the anti-inflammatory effect of sertraline for RWPE-1 cells and EAP mice, and the potential mechanism was regulating the TRPV1 channel. It indicated that sertraline might serve as a complementary anti-inflammatory agent for CP.Keywords: chronic prostatitis, sertraline, RWPE-1, mice, TRPV1

Qiao Zhang,1,&ast; Lei Shi,1,&ast; Yanping Lin,2,&ast; Huirong Dai,1 Yixuan Bai,1 Pan You1 1Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China; 2The Third Hospital of Xiamen, Xiamen, Fujian, 361100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan You, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China, Tel/Fax +86-592-5392620, Email panyou001@yahoo.comPurpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia.Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed.Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS).Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.Keywords: biochemical characteristics, lymphocyte, mitochondrial damage, COVID-19, schizophrenia

Yamei Bai,&ast; Yuqing Chen,&ast; Meng Tian, Jiaojiao Gao, Yulei Song, Xueqing Zhang, Haiyan Yin, Guihua Xu School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, School of Nursing, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Qixia District, Nanjing, Jiangsu Province, 210023, People’s Republic of China, Tel +86-153-6513-2927, Email 7115@njucm.edu.cnPurpose: Social isolation and depression have an impact on cognitive frailty. However, the underlying mechanisms between these variables have not been well defined. This study aims to investigate the mediating role of depressive symptoms in the association between social isolation and cognitive frailty among older adults in China.Methods: From Mar 2023 to Aug 2023, a cross-sectional study was conducted with 496 community-dwelling older adults aged ≥ 60 years in Nanjing, Jiangsu Province, China. Demographic information was collected using the General Information Questionnaire. The Lubben Social Network Scale-6 (LSNS-6), Geriatric Depression Scale 15-item (GDS-15), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and FRAIL scale were used for the questionnaire survey. Multiple linear regression and binary logistic regression were utilized to explore the associations among social isolation, depressive symptoms, and cognitive frailty, and Bootstrap analysis was used to explore the mediating role of depressive symptoms in social isolation and cognitive frailty.Results: Linear regression results revealed that social isolation was positively associated with depressive symptoms (β = 0.873, p < 0.001). Logistic regression analysis showed that social isolation (OR = 1.769, 95% CI = 1.018~3.075) and depressive symptoms (OR = 1.227, 95% CI = 1.108~1.357) were significantly associated with cognitive frailty. Mediation analysis demonstrated that depressive symptoms significantly mediated the relationship between social isolation and cognitive frailty, with an indirect effect of 0.027 (95% CI = 0.003~0.051), and the mediating effect accounted for 23.6% of the total effect.Conclusion: Social isolation is associated with cognitive frailty in community-dwelling older adults, and depressive symptoms partially mediate the effect between social isolation and cognitive frailty. Active promotion of social integration among older individuals is recommended to enhance their mental health, reduce the incidence of cognitive frailty, and foster active aging.Keywords: cognitive frailty, social isolation, depressive symptoms, older adults

Rongyao Liang,1,&ast; Pei Li,1,2,&ast; Na Yang,1 Xiaoyi Xiao,1 Jing Gong,1 Xingyuan Zhang,1 Yunuan Bai,1 Yanlong Chen,1 Zhiyong Xie,3 Qiongfeng Liao1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 3School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiongfeng Liao, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China, Tel +86 2039358081, Email zyfxliao@gzucm.edu.cn Zhiyong Xie, School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China, Tel +86 075523260207, Email xiezhy@mail.sysu.edu.cnPurpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer.Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs.Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately − 9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety.Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs. Keywords: Parabacteroides distasonis, outer membrane vesicles, colon tumor, CXCL10, CD8+ T cells

Yuxin Bai,1,2 Yanjing Zhu,1 Xiaolie He,1 Ruiqi Huang,1,2 Xu Xu,1 Li Yang,1 Zhaojie Wang,1,2 Rongrong Zhu1,2 1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, People’s Republic of China; 2Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200065, People’s Republic of ChinaCorrespondence: Zhaojie Wang; Rongrong Zhu, Email 2013wangzhaojie@tongji.edu.cn; rrzhu@tongji.edu.cnPurpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated.Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells.Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability.Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.Keywords: mouse embryonic stem cell, neural progenitor cells, layered double hydroxide nanoparticles, size-dependent, differentiation, m6A RNA methylation

Xiaoyun Wang,1,2 Yuwei Bai,1,2 Bei Wang1,2 1Institute of Integration of Traditional Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Bei Wang, Email xuewuhenwang@126.comBackground: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression.Methods: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types. We employed the TCGA Pan-Atlas Cancer Genomics Dataset, which is available through the cBioportal platform, to explore genetic alterations in COTL1. We conduct a comprehensive analysis of COTL1, encompassing gene expression, clinical prognosis, RNA modification, immunotherapy, and cancer stemness through SangerBox database. Clinical samples were validated using immunohistochemistry.Results: Our analysis revealed that COTL1 is highly expressed in most cancers and correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts. Furthermore, COTL1 was found to be associated with DNA and RNA stemness in 20 and 22 different tumor types, respectively. Additionally, COTL1 showed positive correlations with immunological checkpoints and immune infiltration cells. It was also linked to tumor mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1), all of which are potential targets for immunotherapies. Moreover, a favorable relationship was demonstrated between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant allele tumor heterogeneity (MATH) with COTL1. Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG.Conclusion: Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.Keywords: COTL1, pan-cancer analysis, cancer therapy, prognosis biomarker, immune cell infiltration

Yue Zhang,&ast; Yafan Bai,&ast; Yi Zhang, Yingjie Du, Min Liu, Jiayu Zhu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery.Patients and Methods: 142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients’ body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS).Results: In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P < 0.05), and a one-day reduction in hospital length of stay was observed in the aggressive warming group (P < 0.05). There was no significant difference in mortality or other postoperative complications, such as cardiovascular complications, wound infection, PONV, pain, fever or headache, between the two groups (P > 0.05).Conclusion: Our results suggest that aggressive thermal management combined with resistive heating mattresses provided improved perioperative body temperature and reduced the incidence of perioperative hypothermia and shivering compared to routine thermal management.Plain Language Summary: ●The incidence of perioperative hypothermia during thyroid surgery was high.●The use of resistive heating mattresses during thyroid surgery can effectively reduce the occurrence of perioperative hypothermia.●It is recommended to take aggressive thermal protection during the operation of minor and medium surgeries, and to continuously monitor the temperature.Keywords: hypothermia, thyroid surgery, resistive heating mattresses, perioperative period

Xu Su,1,&ast; Yimei Zhang,1,&ast; Huilin Zhou,1 Fang Ma,1 Xiaorong Jin,1 Yangjuan Bai,2 Wei Wei,3 Xiong Zhang,1 Min Zhou1 1Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Digestive Surgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650032, People’s Republic of China, Email rebeccamalei@126.comPurpose: Studies had reported some influencing factors of health behavior among patients with coronary heart disease(CHD) after percutaneous coronary intervention(PCI). However, considering that human perceptions are complex, unrestricted and dynamically changing. A longitudinal qualitative study was conducted to explore the determinants of health-related behaviors of patients after PCI and dynamic changes of these determinants at the 1st, 3rd, and 6th months.Patients and Methods: Using purposive sampling, 18 patients undergoing PCI were interviewed. The conventional content analysis method was used to identify categories and subcategories. Semi-structured, face-to-face or telephone in-depth interviews were conducted at the cardiology unit of a tertiary referral hospital in Yunnan Province, China from March 2022 to January 2023.Results: Seven categories with some subcategories were constructed from the data, categorized into three domains. Firstly, individual factors include (i) Personal coping with healthy lifestyle requirements (tried but failed; I can do it), (ii) individual perception and feeling toward disease (knowing about the disease; belief of cure; fears of relapse), and (iii) personal benefits (improved health; meaning of life). Secondly, social factors include (i) social facilitators (family resources; healthcare support), (ii) social barriers (inconvenient medical care service; conflicting information). Finally, cultural factors include (i) way of living (dietary habits; key roles of yan (cigarette) and jiu (alcohol) in Chinese society), (ii) way of thinking (fatalism and Confucian familism).Conclusion: The determinants of health-related behaviors of patients after PCI are multifaceted and dynamic. Different interventions should be formulated to promote patients’ adherence to health behaviors. Moreover, priority should be given to the impact of traditional Chinese philosophy on the health behaviors of patients after PCI, and the health promotion program for these patients should be culturally sensitive. In addition, future research should further explore the determinants of health behaviors among diverse ethnic minorities after PCI, which has not been fully inquired in this study.Keywords: coronary heart disease, percutaneous coronary intervention, health behavior adherence, qualitative research, Chinese traditional culture

Yingliang Wang,1,2,&ast; Shuguang Ju,1,2,&ast; Huimin Zhou,3,&ast; Yaowei Bai,1,2 Chen Zhou,1,2 Jiacheng Liu,1,2 Xiangjun Dong,1,2 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China; 3Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangjun Dong; Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email dongxiangjun3100@163.com; hqzcsxh@sina.comPurpose: To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism.Methods: Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time.Results: The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups.Conclusion: CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.Keywords: calcium peroxide nanoparticles, programmed cell death protein 1 inhibitor, Hepa1-6 model, tumor microenvironment, liver cancer

Bowen Dai,1,2 Yanping Bai,2 HongDa Yu,1,2 Qiuchen Huang,1,2 Lei Wang2 1Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Dermatology and Venerology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Dermatology and Venereology, China-Japan Friendship Hospital, No. 2, Yinghua East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email wanglei010zyy@163.comAbstract: Although psoriasis and systemic lupus erythematosus are both immune abnormalities, there are few reports on Ps combined with SLE in China and abroad. We present a case of a 23-year-old female with a 10-year history of psoriasis, who had a relapse with significant joint symptoms and a PASI score of 35.6, along with several positive antibodies, including antinuclear antibodies, elevated CRP and ESR, and was diagnosed with psoriasis and SLE. She has been treated with secukinumab 300 mg subcutaneously, improving her condition. She is currently being followed up. The PubMed, SCOPUS, and ISI Web of Science databases were thoroughly searched for English studies reporting psoriasis with systemic lupus erythematosus and treated using biologics. Three case reports/series were included after the screening. Our case report provides a reference for clinicians using secukinumab to treat psoriasis combined with SLE. However, further research is needed to determine whether it can be widely used or if there are common signaling pathways that can be interfered with the pathogenesis of the diseases.Keywords: psoriasis, systemic lupus erythematosus, secukinumab

Yun Zhao,1,&ast; Lijun Zhao,1,&ast; Zhaohuang Wang,1 Shuhui Cui,1 Chenchen Ren,2 Li Yang,2 Yang Bai,2 Yuanhang Zhu,2 Jingyan Xie,3 Yujuan Li,3 Xiaoqing Wu,3 Jing Feng,3 Shanqing Man,4 Longmei Huang,4 Xiaoqi Li,4 Xiaotian Yu,4 Jianliu Wang1 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, National Clinical Research Center for Obstetrics and Gynecology, Zhengzhou Key Laboratory of Cervical Disease, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, Henan, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Hangzhou New Horizon Health Technology Co. Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang, Department of Obstetrics and Gynecology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8618901086568, Email wangjianliu1203@163.comObjective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

Linlan Yang,1,&ast; Kaijiong Zhang,2,&ast; Dongming Zheng,1 Yuxin Bai,1 Daifan Yue,1 Lichun Wu,2 Han Ling,2 Sujiao Ni,2 Haimin Zou,2 Bo Ye,2 Chang Liu,2 Yao Deng,2 Qiancheng Liu,3 Yan Li,1 Dongsheng Wang1,2 1College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Clinical Laboratory of Mianyang People’s Hospital, Mianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Wang, Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangdongshengnc@163.com Yan Li, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email Liliana@cdutcm.edu.cnAbstract: In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.Keywords: platelet, tumor, targeted platelet, platelet membranes, stimuli-responsive drug delivery system, nanoparticle

Chongmei Tian,1,&ast; Jianqin Song,2,&ast; Delian Huang,3 Siwei Wang,4 Yaping Zhao,1 Liping Fu,1 Xueyu Fan,5 Tianhong Ma,6 Yongfeng Bai5 1Department of Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Traditional Chinese Medicine, Hangzhou Linping District Hospital of Integrated Chinese and Western Medicine, Hangzhou, People’s Republic of China; 3School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Core Facility, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China; 5Department of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, 324000, People’s Republic of China; 6Department of Pharmacy, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, 314001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongfeng Bai; Tianhong Ma, Email bai.yongfeng@163.com; 15990312207@163.com

Yuelan Tao,1,2 Wei Chen,3 Hongbing Xu,1 Jiacheng Xu,1,2 Huan Yang,4 Xin Luo,1 Miaomiao Chen,5 Jie He,1,2 Yuxiang Bai,1,&ast; Hongbo Qi1,2,6,&ast; 1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Emergency & Intensive Care Units, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, 404100, People’s Republic of China; 5Maternal and Child Health Hospital of Hubei Province, Wuhan City, Hubei Province, 430070, People’s Republic of China; 6Women and Children’s Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxiang Bai; Hongbo Qi, Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8602389011007, Email yuxiangbaicq@163.com; qihongbocy@gmail.comBackground: A recent study has reported that maternal obesity is linked to placental oxidative damage and premature senescence. NADPH oxidase 4 (NOX4) is massively expressed in adipose tissue, and its induced reactive oxygen species have been found to contribute to cellular senescence. While, whether, in obese pregnancy, adipose tissue-derived NOX4 is the considerable cause of placental senescence remained elusive.Methods: This study collected term placentas from obese and normal pregnancies and obese pregnant mouse model was constructed by a high fat diet to explore placental senescence. Furthermore, adipocyte-derived exosomes were isolated from primary adipocyte medium of obese and normal pregnancies to examine their effect on placenta functions in vivo and vitro.Results: The placenta from the obese group showed a significant increase in placental oxidative damage and senescence. Exosomes from obese adipocytes contained copies of NOX4, and when cocultured with HTR8/SVneo cells, they induced severe oxidative damage, cellular senescence, and suppressed proliferation and invasion functions when compared with the control group. In vivo, adipocyte-derived NOX4-containing exosomes could induce placental oxidative damage and senescence, ultimately leading to adverse pregnancy outcomes.Conclusion: In obesity, adipose tissue can secrete exosomes containing NOX4 which can be delivered to trophoblast resulting in severe DNA oxidative damage and premature placental senescence, ultimately leading to adverse pregnancy outcomes.Keywords: maternal obesity, placental premature senescence, adipose tissue, exosome, NADPH oxidase 4, oxidative damage

Xinghua Guo,1,2,&ast; Pan Song,1,2,&ast; Feng Li,1,2,&ast; Qihao Yan,1,2,&ast; Yan Bai,3 Jincan He,3 Qishi Che,4 Hua Cao,5 Jiao Guo,2 Zhengquan Su1 1Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 2Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 3School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, People’s Republic of China; 4Guangzhou Rainhome Pharm & Tech Co., Ltd, Science City, Guangzhou, 510663, People’s Republic of China; 5School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengquan Su, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Tel +86-20-3935-2067, Fax +86-20-3935-2067, Email suzhq@scnu.edu.cnAbstract: Bone, like most organs, has the ability to heal naturally and can be repaired slowly when it is slightly injured. However, in the case of bone defects caused by diseases or large shocks, surgical intervention and treatment of bone substitutes are needed, and drugs are actively matched to promote osteogenesis or prevent infection. Oral administration or injection for systemic therapy is a common way of administration in clinic, although it is not suitable for the long treatment cycle of bone tissue, and the drugs cannot exert the greatest effect or even produce toxic and side effects. In order to solve this problem, the structure or carrier simulating natural bone tissue is constructed to control the loading or release of the preparation with osteogenic potential, thus accelerating the repair of bone defect. Bioactive materials provide potential advantages for bone tissue regeneration, such as physical support, cell coverage and growth factors. In this review, we discuss the application of bone scaffolds with different structural characteristics made of polymers, ceramics and other composite materials in bone regeneration engineering and drug release, and look forward to its prospect.Graphical Abstract: Keywords: bone scaffold, drug loading, slow release, osteogenesis, biomaterial

Chenxi Liao,1,&ast; Siyu Tao,1,&ast; Yan Xiong,2,&ast; Jingyang Dai,3 Yu Bai,4 Xue Wang,1 Yuan Li,5 Ping Wu1 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Osteoporosis, Huaxi Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Traditional Chinese Medicine, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of China; 4Department of Traditional Chinese Medicine, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China; 5Department of Rheumatology, The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Wu, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email wuping_33@163.comPurpose: To investigate the effects of moxibustion in relieving pain, and other clinical symptoms for patients with rheumatoid arthritis (RA), and explore the potential mechanism of moxibustion treatment for RA.Patients and Methods: Seventy qualified RA patients were randomly assigned in a 1:1 ratio to the moxibustion group or the routine group. The routine group only took oral methotrexate tablets and folic acid tablets. The moxibustion group was treated with moxibustion based on oral pharmaceutical. Moxibustion was performed two times weekly for 8 weeks, a total of 16 sessions. Patients scored their pain on a visual analog scale (VAS). The American College of Rheumatology improvement criteria of 20%, 50% and 70% (ACR20, ACR50 and ACR70) after treatment were investigated. Clinical symptoms, a disease activity score using 28 joint counts (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), health assessment questionnaire (HAQ), interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) of RA patients were analyzed before and after treatment.Results: After treatment, the VAS scores, tender and swollen joint counts, morning stiffness scores, disease activity scores (DAS28, SDAI, CDAI), HAQ scores in the two groups were both improved, and the effects of moxibustion group were more obvious (P < 0.05). The ACR20 and ACR50 of the moxibustion group were greater than that of the routine group (P < 0.05), no significant difference of the ACR70 existed between the two groups (P > 0.05). In addition, the decreases of IL-1β, TNF-α, VEGF of the moxibustion group were better than that of the routine group (P < 0.05).Conclusion: Moxibustion could effectively relieve pain, ameliorate the clinical symptoms, and decrease the disease activity of RA. The potential mechanism may be the decrease in the level of serum inflammatory factors.Keywords: moxibustion, rheumatoid arthritis, pain, inflammatory factor

Jie Liu,1,&ast; Yilei Ma,2,&ast; Wanli Xie,1,&ast; Xia Li,1 Yanting Wang,1 Zhenzhen Xu,1 Yunxiao Bai,1 Ping Yin,2 Qingping Wu1 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingping Wu, Email wqp1968@126.comBackground: The predictive effect of systemic inflammatory factors on postoperative pulmonary complications in elderly patients remains unclear. In addition, machine learning models are rarely used in prediction models for elderly patients.Patients and Methods: We retrospectively evaluated elderly patients who underwent general anesthesia during a 6-year period. Eligible patients were randomly assigned in a 7:3 ratio to the development group and validation group. The Least logistic absolute shrinkage and selection operator (LASSO) regression model and multiple logistic regression analysis were used to select the optimal feature. The discrimination, calibration and net reclassification improvement (NRI) of the final model were compared with “the Assess Respiratory Risk in Surgical Patients in Catalonia” (ARISCAT) model.Results: Of the 9775 patients analyzed, 8.31% developed PPCs. The final model included age, preoperative SpO2, ANS (the Albumin/NLR Score), operation time, and red blood cells (RBC) transfusion. The concordance index (C-index) values of the model for the development cohort and the validation cohort were 0.740 and 0.748, respectively. The P values of the Hosmer–Lemeshow test in two cohorts were insignificant. Our model outperformed ARISCAT model, with C-index (0.740 VS 0.717, P = 0.003) and NRI (0.117, P < 0.001).Conclusion: Based on LASSO machine learning algorithm, we constructed a prediction model superior to ARISCAT model in predicting the risk of PPCs. Clinicians could utilize these predictors to optimize prospective and preventive interventions in this patient population.Keywords: older adult, postoperative complications, ANS, the albumin/NLR score, risk factors

Sihua Wen,1,&ast; Kai Yang,1,&ast; Yunfeng Bai,2 Yanan Wu,1 Ding Liu,1 Xu Wu,1 Xiaofei Zhang,1 Jing Sun1 1Department of Pharmaceutics, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 2Shaanxi Dongtai Pharmaceutical Co., Ltd, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofei Zhang; Jing Sun, Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Tel +86 177 7003 7322, Fax +86 029-38185333, Email 2051028@sntcm.edu.cn; sunjing202203@126.comPurpose: To study the active components, drug targets and mechanism of Schisandra chinensis (S.chinensis) combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF).Methods: Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which S.chinensis combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of S. chinensis combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot.Results: Network pharmacology combined with experimental validation suggests that the mechanism of action of S.chinensis combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, S. chinensis combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1β and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of S.chinensis and CQ10 was more effective compared with CQ10 alone, ie, the ability of S.chinensis combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway.Conclusion: The therapeutic effect of S.chinensis combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.Graphical Abstract: Keywords: Schisandra chinensis, coenzyme Q10, network pharmacology, molecular docking, mechanism validation, heart failure

Jingjing Zhong, Ming Wei, Chunxia Yang, Yudong Yin, Yu Bai, Ran Li, Li Gu Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Li Gu, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100000, People’s Republic of China, Email guli2013227@foxmail.comPurpose: Since community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized, the molecular epidemiology of CA-MRSA in China has been diverse. It is unclear whether different sites of CA-MRSA infection differ in antimicrobial resistance and clinical characteristics. The purpose of this study was to identify the molecular types, virulence factors and antimicrobial resistance of CA-MRSA strains and to analyze the clinical characteristics of different sites of CA-MRSA infection.Methods: 26 CA-MRSA strains were screened from Beijing Chao-Yang Hospital from 2014 to 2022. SCCmec type, MLST type, spa type, Panton–Valentine leukocidin (PVL), hemolysin α (Hla), phenolic soluble regulatory protein α (PSMα), toxic shock syndrome toxin-1 (TSST-1), and enterotoxin (SE) A to E were detected by PCR and gene sequencing. Antimicrobial susceptibility tests and the clinical features of CA-MRSA infection cases were collected for statistical analysis.Results: The predominant type of CA-MRSA was ST59-t437-IV. New non-epidemic types, SCCmec VII, were also found. PVL was seen in 65.4% of CA-MRSA strains and TSST-1 was only be detected in 3.8% of CA-MRSA strain which caused poor prognosis. There were three types of infections: pneumonia (61.5%), infective endocarditis (7.7%), and skin and soft tissue infections (SSTIs) (30.8%). CA-MRSA pneumonia cases were secondary to influenza infection (37.5%). Patients with CA-MRSA-associated infective endocarditis were more likely to have underlying cardiac diseases. Patients with CA-MRSA-associated SSTIs were more likely to have a history of diabetes mellitus, and strains in this group were more susceptible to erythromycin and clindamycin.Conclusion: ST59-t437-IV was the primary CA-MRSA type in our research and in China. We proposed that TSST-1 might be one of the indicators to predict the severity and prognosis of CA-MRSA infection. Different sites of CA-MRSA infection had difference in antibiotics susceptibility testing and underlying diseases of patients. It could provide a new perspective on treating different types of CA-MRSA infection.Keywords: community, acquired methicillin, resistant Staphylococcus aureus, staphylococcal chromosomal cassette mec type, Panton-Valentine leukocidin, antibiotic resistance, pneumonia

Yuan Ze,1 Huiming Tu,2 Lin Zhang,3,4 Yu Bai,5 Yilin Ren,2 Xin Chen,1 Yuzheng Xue,2 Renjuan Sun,6 Yuling Yang,7 Jie Yang,2 Xuan Zhou,2 Li Liu8 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China; 4School of Population Medicine and Public Health, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Gastroenterology, Changhai Hospital of Shanghai, Shanghai, People’s Republic of China; 6Outpatient Nursing department, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 7Nursing department of Geriatrics Ward, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 8Data Center, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Huiming Tu, Department of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86-13861753621, Email tuhuiming1891@163.comObjective: To compare the screening efficacy of colonoscopy and pathologically confirmed single and combined Asia-Pacific colorectal screening (APCS), faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing protocols.Methods: From April 2021 to April 2022, 842 volunteers participated in primary colorectal cancer (CRC) screenings using APCS scoring, FIT and sDNA testing and 115 underwent a colonoscopy. One hundred high-risk participants were then identified from the results of both processes. The differences in the three CRC screening tests in combination with the colonoscopy pathology diagnostics were evaluated using Cochran’s Q test, the Dunn–Bonferroni test and area under the receiver operating characteristic curve (AUC) value analysis.Results: Both FIT and sDNA testing demonstrated a 100% performance in detecting CRC. For advanced adenoma, the sensitivity of the FIT + sDNA test scheme (double positive) was 29.2%, and the sensitivities of the combined FIT + sDNA test and APCS scoring + sDNA test schemes were 62.5% and 95.8%, respectively. The FIT + sDNA testing kappa value of advanced colorectal neoplasia was 0.344 (p = 0.011). The sensitivity for nonadvanced adenoma of the APCS score + sDNA test scheme was 91.1%. In terms of positive results, the sensitivity of the APCS score + FIT + sDNA detection protocol was significantly higher than that of the APCS score, FIT, sDNA detection, and FIT + sDNA detection methods (adjusted p < 0.001, respectively). For the FIT + sDNA test, the kappa value was 0.220 (p = 0.015) and the AUC was 0.634 (p = 0.037). The specificity of the FIT + sDNA test scheme was 69.0%.Conclusion: The FIT + sDNA test scheme demonstrated superior diagnostic efficacy, and the combined APCS score + FIT + sDNA test scheme demonstrated remarkable improvements in CRC screening efficiency and sensitivity for detecting positive lesions.Keywords: faecal immunochemical testing, stool DNA test, colonoscopy, primary screening, colorectal cancer

Jun-Hong Ma,1 Yuan Bai,2,3 De-Shun Xie,4 Gui-Fang Yang1 1Neurology Department, Heze Municipal Hospital, Heze, Shandong Province, 274000, People’s Republic of China; 2Vascular Surgery Department, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 3Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4CT Department, Heze Municipal Hospital, Heze, Shandong Province, People’s Republic of ChinaCorrespondence: Yuan Bai, Vascular Surgery Department, Shanxi Bethune Hospital, No. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86 13934660965, Email yuanbai_by1830@163.comObjective: To explore the current status of interruption events in nursing document writing in the intensive care unit (ICU) using a cross-sectional survey.Methods: Between May and October 2021, the convenience sampling method was used to observe the interruption events in nursing document writing in the ICU. A total of 54 nurses and 7 indicators were observed: the start time, end time, interruption period, source, type, duration and outcome of interruption events.Results: A total of 438 interruption events in nursing document writing occurred in 85.955 hours, with a frequency of 5.093 times/hour and a duration of 4787.00 (1152.00, 13,109.00) seconds. The frequency of interruption events in nursing document writing was the highest (11 times/hour) and the duration was the longest (9581.50 seconds) from 08:00 to 12:00. The main sources of interruptions for nurses with 10 or more years of service or with the professional title of nurse are nurses themselves and their colleagues. The main sources of interruptions for nurses who have been in charge for 10 years or over are the working environment and doctors. This intervention in work continuity occurs unexpectedly; however, if adjustments are made to nursing procedures, the interruption can be terminated rapidly or adverse consequences can be avoided. Years of working experience, seniority level, interruption time periods and professional titles were independent factors influencing the number of interruption events, and they were all positively correlated. The results of this study show that there were statistically significant differences in the incidence of negative outcomes among ICU nurses with varying years of working experience and professional titles.Conclusion: Interruptions in nursing document writing have high frequency, complex sources and multiple types. For senior nurses, the outcome was predominantly positive, while for junior nurses, it was predominantly negative.Keywords: ICU, nurses, nursing documents, interruption events

Bao Sun,1,2,&ast; Yingshuang Tang,2,&ast; Dan Chen,3 Yanning Bai,4 Yuanyuan Zhang,5 Suning Chen,2 Yi Qiao,2 Jingwen Wang2 1Department of Pharmacy, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Pharmacy, Xijing Hospital, Fourth Military Medical Unversity, Xi’an, Shaanxi, People’s Republic of China; 3Department of pharmacy, 404 Hospital of Mianyang, Mianyang, Sichuan, People’s Republic of China; 4Department of Clinical Pharmacy, Yan’ an University Affiliated Hospital, Yan’an, Shaanxi, People’s Republic of China; 5Department of Pharmacy, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Qiao; Jingwen Wang, Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi, People’s Republic of China, Email 694305040@qq.com; wangjingwen8021@163.comAbstract: Biliary cryptococcosis infection is extremely rare and difficult for preoperative diagnosis. We report a rare case of 61-year-old woman with biliary cryptococcal infection. To explore the general rule and case characteristics of biliary cryptococcal infection and provide a reference for future diagnosis and treatment, we consulted the PubMed database for reported biliary cryptococcal infection from 1985 to 2021. Including the present one, we collected 12 reports, among which half were male and five were younger than 18 years old. Clinical manifestations were mainly jaundice, while in vitro examination revealed bile duct dilatation and bile duct stenosis. In 8 cases (66.67%), symptoms improved or healed after antifungal treatment. Although preoperative misdiagnosis of cryptococcal infection is high, the antifungal treatment is quite effective. Thus, early accurate diagnosis can effectively improve the cure rate of biliary cryptococcosis infected patients.Keywords: biliary cryptococcosis, obstructive jaundice, Cryptococcus neoformans, literature analysis

Weitong Li,1,&ast; Haiyan Yin,1,&ast; Yulei Song,1 Wenjing Tu,1 Lulu Wang,1 Yongqi Liang,1 Yamei Bai,1,&ast; Guihua Xu2,&ast; 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Email 7115@njucm.edu.cnBackground: Social isolation is a serious and pervasive health issue among older people, and it is difficult to identify and assess effectively. Based on a thorough and scientific evaluation index system, AHP-Fuzzy comprehensive evaluation could be a valuable technique.Objective: It is crucial to establish interventions that focus on risk factors for the prevention of social isolation in order to give a strong scientific foundation for enhancing older people’s health habits. This can be achieved by using a fuzzy comprehensive evaluation method to assess the risk of social isolation in older people.Methods: A hundred community members over 60 from Nanjing were selected as the evaluation subjects in China. After the element layer was split into three categories of “social risk, economic risk, and cultural risk” using the analytic hierarchy process approach, a total of 22 assessment indicators were picked to develop a risk evaluation index system.Results: The risk level of social isolation belonging to the “low risk, relatively low risk, medium risk, relatively high risk, high risk” of membership degree are respectively “ 0.3392, 0.2632, 0.2257, 0.1069, 0.0650”. Fuzzy comprehensive evaluation analysis showed that social relations (0.4934), monthly income (0.4654), health status (0.5960) were significant factors of social isolation risk in older people. The results showed that factors related to social risk had the most significant impact on social isolation.Conclusion: It is scientific and feasible to construct the risk evaluation index model of social isolation risk for the elderly by using AHP-Fuzzy comprehensive evaluation method. In preventing social isolation of older people in the future, we should pay attention to the impact of social and cultural factors on them, and provide practical intervention programs and references from the government, community, family.Keywords: AHP, fuzzy comprehensive evaluation method, social isolation, older people

Yifeng Chen,&ast; Jian Zhang,&ast; Fengsu Hou, Yuanhan Bai Shenzhen Mental Health Center, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhan Bai, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, No. 77 Zhenbi Road, Pingshan District, Shenzhen City, 518118, People’s Republic of China, Email baiyuanhan@163.comBackground: Lithium has been widely used to treat bipolar disorder (BD), although its adherence is rarely reported in China. This study aimed to explore the rate of lithium adherence and its associated factors in patients with BD, which has rarely been reported in China.Methods: We conducted a cross-sectional study among patients in Shenzhen Mental Health Center (Shenzhen Kangning Hospital), who were aged 12 years or above, were diagnosed with BD based on the International Classification of Diseases, tenth edition (ICD-10), and had been on lithium for at least 1 month. We collected information on sociodemographic and clinical characteristics and on knowledge about and attitudes toward lithium. We also investigated patients’ concerns while taking lithium and where they can and wish to obtain information on lithium.Results: Of the 244 enrolled patients and 221 patients aged 18 years or older, 52% and 50% disclosed low adherence to lithium, respectively. Factors associated with poor lithium adherence were a younger age (odds ratio (OR): 0.962, 95% confidence interval (CI): 0.933– 0.992), female sex (OR: 2.171, 95% CI: 1.146– 4.112), and no hospitalization history (OR: 0.389, 95% CI: 0.217– 0.689) for the full sample, and more years of education (OR: 4.086, 95% CI: 1.397– 11.946) and fewer hospitalizations (OR: 0.615, 95% CI: 0.467– 0.809) for patients aged 18 years or older. Less knowledge of periodic tests conducted during lithium treatment played a critical role in low lithium adherence (regression analysis of the full sample: OR: 0.642, 95% CI: 0.532– 0.775, regression analysis of subgroups: OR: 0.609, 95% CI: 0.500– 0.742). The treatment duration was a major concern among patients on lithium, and patients preferred obtaining lithium-associated information through health services and WeChat.Conclusion: The rate of lithium adherence was low in this study. Psychoeducation to increase lithium compliance should mainly focus on patients who are young and provide thorough background information on lithium. Health services should actively provide lithium-associated information. A greater need for medication information based on WeChat was observed, implying its potential role in adherence-related psychoeducation.Keywords: bipolar disorder, lithium, adherence, China

Lei Lei,1 Yihua Bai,1 Yang Fan,1 Yaling Li,1 Hongying Jiang,1 Jiaping Wang2 1Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Radiology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yihua Bai, Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email baiyihua@kmmu.edu.cnBackground: Diabetic nephropathy (DN) is a primary driver of end-stage renal disease. Given the heterogeneity of renal lesions and the complex mechanisms of DN, the present-day diagnostic approach remains highly controversial. We aimed to design a diagnostic model by bioinformatics methods for discriminating DN patients from normal subjects.Methods: In this study, transcriptome sequencing was performed on 6 clinical samples (3 from DN patients and 3 from healthy volunteers) from the Second Affiliated Hospital of Kunming Medical University. Construction of a competing endogenous RNA (ceRNA) network based on differentially expressed (DE)-mRNAs and -long noncoding RNAs (lncRNAs). Subsequently, the CytoHubba plugin was used to identify hub genes from DE-mRNAs in the ceRNA network and to perform functional enrichment analysis on them. The least absolute shrinkage and selection operator (LASSO) regression analysis was responsible for screening the diagnostic biomarkers from hub genes and assessing their diagnostic power using ROC curves. The pathways involved in hub genes were revealed by single-gene Gene Set Enrichment Analysis (GSEA). Moreover, we verified the expression levels of diagnostic biomarkers by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot.Results: A total of 10 hub genes were screened from the ceRNA network, which appeared to be associated with the viral infection, kidney development, and regulation of immune and inflammatory responses. Subsequently, LASSO regression analysis established a diagnostic model consisting of DDX58, SAMD9L, and TLR6 with a robust diagnostic potency (AUC = 1). Similarly, single-gene GSEA showed a strong association of these diagnostic biomarkers with the viral infection. Furthermore, PCR and Western blot demonstrated showed that DDX58, SAMD9L, and TLR6 were upregulated in DN patients at both transcriptome and protein levels compared to healthy controls.Conclusion: We confirmed that differentially expressed hub genes may be novel diagnostic biomarkers in DN.Keywords: diabetic nephropathy, DN, diagnosis, ceRNA, biomarker

Chun-Shuang Guan,1,&ast; Zhi-Juan Liu,2,&ast; Yan-Ni Du,1,&ast; Hui Chen,1 Yan Bai,1 Zhi-Bin Lv,1 Yan-Li Xu,2 Ru-Ming Xie,1,&ast; Bu-Dong Chen1,&ast; 1Department of Radiology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Chronic Disease Management Centre, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ru-Ming Xie; Bu-Dong Chen, Tel +8613911320739 ; +8613801358954, Email mingrux1@163.com; chenbudong00@126.comPurpose: To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge.Patients and Methods: A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher’s exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0.Results: There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe–critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient’s condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%).Conclusion: The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients’ age and disease conditions were positively correlated with residual lesions.Keywords: COVID-19, follow-up studies, tomography, X-ray computed, lung

Lei Zhang, Jun Zhao, Yun Bai, Xiuping Liu Department of Obstetrics and Gynecology, the Third Hospital of Hebei Medical University, Shijiazhuang City, 050051, People’s Republic of ChinaCorrespondence: Lei Zhang, Department of Obstetrics and Gynecology, the third hospital of Hebei Medical University, No. 139 of Ziqiang Road, Qiaoxi District, Shijiazhuang City, Hebei Province, 050051, People’s Republic of China, Tel +86-0311-88602058, Email leizhang1442@163.comObjective: This study aimed to compare fertility outcomes in patients who underwent different laparoscopic surgeries and to determine the most beneficial surgical treatment for tubal ectopic pregnancy (EP) patients who wished to become pregnant in the future.Methods: In this retrospective study, patients aged 18– 36 years, who had been diagnosed with a tubal EP in our hospital, were enrolled. Based on the treatment methods, the patients were divided into three groups, ie a salpingectomy group, a salpingotomy with suturing group and a salpingotomy without suturing group. The follow-up time for the enrolled patients was more than three years. Serum beta (β)-human chorionic gonadotropin (β-HCG) levels were monitored after surgery. The intrauterine pregnancy (IUP) rate at 12, 24 and 36 months postoperatively, and recurrent EP rate were compared.Results: The median time for β-HCG level returning to normal in the salpingectomy group was much shorter than in the salpingotomy with suturing or salpingotomy without suturing groups (P < 0.001). The 12, 24 and 36-month IUP rates among the three groups were not significantly different. A recurrent EP was found in only one patient in the salpingotomy with suturing group and two patients in the salpingotomy without suturing group.Conclusion: In this study, we found that salpingectomy and salpingotomy with or without suturing methods reflected no significant differences in fertility outcomes for tubal EP patients.Keywords: ectopic pregnancy, salpingectomy, salpingotomy, intrauterine pregnancy, fertility

Hang Zhou,1 Fang Ma,2 Yi Zhang,2 Youqin Tan,2 Yangjuan Bai,3 Qiulan Hu,4 Wei Wei,5 Yanjiao Wang1 1Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Cardiology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4ICU in Geriatric Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Neurosurgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Yanjiao Wang, Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, 295#, Xichang Road, Kunming, People’s Republic of China, Tel +86-138-889-29699, Email mayuwyj1974@126.com Correspondence: Fang Ma, Department of Nursing, The First Affiliated Hospital of Kunming Medical University, 295#, Xichang Road, Kunming, People’s Republic of China, Tel +86-159-251-89957, Email rebeccamalei@126.comPurpose: To explore perceptions of antipsychotics associated side-effects among family caregivers of patients with schizophrenia.Patients and Methods: A descriptive qualitative study was applied in a tertiary referral hospital in China. Purposeful sampling of 18 family caregivers of patients with schizophrenia were interviewed about their perceptions towards antipsychotics related side effects.Results: According to content analysis, three themes emerged from the data: (a) nightmare in the treatment with the categories of sleep disturbances; physical impairment; appearance impairment; (b) opposite attitudes toward side-effect with the categories of being vigilant; do not care; (c) diverse ways of coping side-effects with the categories of asking for help from professionals; self-determined; try any quack’s prescription.Conclusion: The side effects of antipsychotics not only damage the health of patients, but also increase the burden and stress of caregivers. However, caregivers have different attitudes and coping styles about the side effects of antipsychotics. Health professionals should be aware of the influence of individual background and cultural factors on caregivers’ attitudes towards drug side effects. Furthermore, health professionals should also provide caregivers with knowledge about drug side effects, coping skills, and appropriate management strategies to promote health outcomes for people with schizophrenia.Keywords: schizophrenia, family caregivers, antipsychotics, drug side effects, content analysis

Yixuan Bai,1 Chenggang Lei,2 Na Zhang,1 Yuhui Liu,1 Zhengyu Hu,3 Yan Li,4 Ran Qi5 1Department of Digestive Internal Medicine, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao, People’s Republic of China; 3Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Gastroenterology, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Department of General Surgery, Tongji Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Ran Qi, Department of General Surgery, Tongji Hospital of Tongji University, School of Medicine, Tongji University, 389 Xincun Road, Putuo District, Shanghai, 200092, People’s Republic of China, Email 2011070@tongji.edu.cnAim: The aim of this study was to identify clinical endoscopic indicators related to peri-ulcerative mucosal inflammation and to analyze whether the degree of peri-ulcerative mucosal inflammation appearance is an independent risk factor for gastric ulcer rebleeding.Methods: We conducted a retrospective study that included patients with gastric ulcer bleeding who were hospitalized at three medical centers in China from January 1, 2016 to December 31, 2019. Ulcer rebleeding that occurred within 30 days of successful initial hemostasis was analyzed to determine whether this event was related to the degree of peri-ulcerative mucosal inflammation appearance or other mucosal inflammation-related factors.Results: We enrolled 1111 patients and determined that GBS-Rebleeding-ROC (P< 0.001), age (P=0.01), use of NSAIDs (P=0.001), bile reflux (P< 0.001), and Helicobacter pylori (P< 0.001) are all risk factors for peri-ulcerative mucosal inflammation appearance. Through multivariate analysis, we determined that severe peri-ulcerative mucosal inflammation appearance (P=0.002) was an independent risk factor for ulcer rebleeding within 30 days. Finally, we developed a risk assessment model using factors associated with mucosal inflammation that may be useful for early prediction of rebleeding.Conclusion: The risk factors for peri-ulcerative mucosal inflammation appearance were identified. Severe peri-ulcerative mucosal inflammation appearance is an independent risk factor for ulcer rebleeding.Keywords: gastric ulcer, peptic ulcer bleeding, risk factors, rebleeding, peri-ulcerative mucosal inflammation

Liurui Dou, Mingyue Shi, Juanjuan Song, Xiaona Niu, Junwei Niu, Shengjie Wei, Dan Li, Yanliang Bai, Kai Sun Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, Henan, People’s Republic of ChinaCorrespondence: Kai Sun; Yanliang BaiDepartment of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, No. 7 Weiwu Road, Jinshui District Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86-18237110038; +86-13783605211, Email sunkai@cellscience.org; yanliangbai@126.comBackground: The ratio of C-reactive protein to albumin (CAR) is an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in several solid tumours and chronic lymphocytic leukaemia (CLL). However, no studies have investigated the prognostic value of the CAR in patients with acute myeloid leukaemia (AML).Objectives and Methods: We retrospectively analysed 212 newly diagnosed non-M3 AML patients. Using the receiver operating characteristic curve (ROC) method, the optimal cut-off value for CAR was determined. We investigated the correlations of the pretreatment CAR levels with clinical characteristics, treatment response of induction chemotherapy, overall survival (OS) and event-free survival (EFS). We also assessed the prognostic value of the CAR compared with other inflammation-based prognostic parameters by the area under the curve (AUC).Results: According to the ROC curve, the optimal cut-off value of CAR was 1.015. CAR was associated with age, C-reactive protein (CRP) levels, albumin levels, ferritin levels, bone marrow blast percentage, French-American-British (FAB) classification, immunophenotype and 2017 European Leukemia Net (2017 ELN) risk stratification. Importantly, we found that high CAR was a powerful indicator of a lower complete remission (CR) rate (p< 0.001), worse OS (p< 0.001) and worse EFS (p< 0.001). Subgroup analysis showed that a high CAR was associated with shorter OS and EFS in patients with intermediate risk stratification or those aged ≤ 65 years or those without haematopoietic stem cell transplantation (HSCT). In the multivariate analysis, the CAR was an independent prognostic factor for OS and EFS. Furthermore, the predictive value of CAR for OS is superior to that of CRP, albumin and GPS in de novo AML patients aged ≤ 65 years old.Conclusion: CAR is a simple and effective prognostic marker in patients with AML. It could be an additional prognostic factor that help further precise the current risk stratification of non-M3 AML, particularly for patients in intermediate risk stratification and those aged ≤ 65 years and those who did not undergo HSCT.Keywords: acute myeloid leukaemia, C-reactive protein to albumin ratio, prognosis

Nan Liu,1 Yuchun Bai,1 Xing Li,1 Yanfei Zhang2 1College of Public Health of Xi’an FanYi University, Xian, Shaanxi Province, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xian, Shaanxi Province, People’s Republic of ChinaCorrespondence: Yanfei ZhangThe Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi Province, People’s Republic of China, Tel/Fax +86-29-87679301, Email zhangyanfei723@163.comPurpose: Scabies is a common, neglected, and a major health concern skin disease in the world. Improper care may produce a series of complications and even lead to the spread of diseases. Nursing students, as future health-care workers, are vital to the prevention and care of diseases. However, to date, few studies have focused on the basis of their disease cognition for scabies. This study aims to evaluate the level of undergraduate nursing students’ awareness of scabies disease.Methods: A questionnaire survey was conducted among all undergraduate nursing students in Xi’an FanYi University, Xian, Shaanxi Province, China.Results: All the 132 undergraduate nursing students completed the questionnaire. The true ignorance rate of scabies in this survey was 82.6%. However, among the 56 students (42.4% of total) who thought they knew about the disease. Only 23 students (17.4% of the samples) had 75% or more satisfactory knowledge. Fewer students claimed that they had read about the itchy-mite-disease in books (N = 20, 15.2%). Compared with college textbooks (P-value < 0.05) and medical books (P-value < 0.05), other books (medical journals) provide more information about scabies. Nearly half of the students did not know that the scabies can be contagious. All students expressed their willingness to learn about scabies knowledge and participate in the diagnosis and treatment of scabies (100%).Conclusion: This study shows that undergraduate nursing students have a poor level of knowledge about scabies. There is an urgent need to improve nursing students’ awareness of scabies and increase their knowledge base, so as to strengthen the standardized nursing of scabies and reduce the prevalence of scabies.Keywords: scabies, knowledge, nursing education, nursing students, healthcare

Tongqiang Li,1,2,&ast; Qin Shi,1,2,&ast; Jiacheng Liu,1,2,&ast; Yingliang Wang,1,2 Chen Zhou,1,2 Chaoyang Wang,1,2 Shuguang Ju,1,2 Songjiang Huang,1,2 Chongtu Yang,1,2 Yang Chen,1,2 Yaowei Bai,1,2 Bin Xiong1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin XiongDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, People’s Republic of ChinaEmail herr_xiong@126.comObjective: To investigate the efficiency and safety of callispheres beads loaded with donafenib (DCBs) for embolization in a VX2 liver tumor, as well as the improvement of tumor angiogenesis following embolization.Methods: Forty New Zealand white rabbit VX2 liver tumors were treated with four different drugs via the hepatic artery: NS (normal saline), CB (blank callispheres beads), ACB (adriamycin-loaded callispheres beads) and DCB (DCBs). Hematoxylin-eosin staining was performed to assess tumor necrosis, while MRI was employed to detect the changes in tumor size. The safety was evaluated by the liver and kidney function parameters, and the immunofluorescence and immunohistochemical staining were performed to reflect the tumor hypoxia and tumor angiogenesis following embolization.Results: The DCB group had the smallest tumor growth rate, but the tumor necrosis rate was the highest of the four groups. Compared to the CB and ACB groups, the DCB group did not aggravate the liver damage and had no influence on kidney function. The staining results showed that, although the tumor hypoxia deteriorated after DCBs embolization, the expression of VEGF (vascular endothelial growth factor) reduced, thus inhibiting tumor angiogenesis.Conclusion: DCB administration via hepatic artery is an effective and safe treatment for a preclinical liver cancer model, with the unique benefit of suppressing tumor angiogenesis following embolization.Keywords: hepatocellular carcinoma, donafenib, transcatheter arterial chemoembolization, tumor angiogenesis, efficacy, safety

Min Zhong,1 Xu Jiang,1 Sha Zhu,1 Ruxin Gu,1 Yu Bai,2 Hong He,3 Yang Pan,1 Pingyi Xu,4 Jun Yan,1 Li Zhang1 1Department of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Biological Sciences, University of Toronto Scarborough, Toronto, ON, Canada; 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 4Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Li Zhang; Jun YanDepartment of Geriatric Neurology, Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of ChinaEmail neuro_zhangli@163.com; 815473709@qq.comPurpose: Sleep disturbance is one of the common symptoms in Parkinson’s disease (PD). The study of sleep disturbance used to concentrate on treated PD. This study aimed to investigate the factors that are associated with the sleep quality of drug-naïve patients with PD.Patients and Methods: All participants were interviewed using a standard questionnaire to collect basic information. PD severity, depression symptoms, anxiety symptoms, sleep quality, cognitive status, life quality, and the presence of rapid eye movement (REM) sleep behavior disorder (RBD) and minor hallucination were assessed using corresponding rating scales. The patients with a Pittsburgh Sleep Quality Index score ≤ 6 fell into the poor sleep group, and those with REM Sleep Behavior Disorder Screening Questionnaire score ≥ 5 were considered to have probable RBD.Results: Seventy drug-naive patients with PD and 30 healthy controls matched for age, sex, and education were recruited. Up to 41.4% of the patients suffered from sleep disturbance, and 24.3% of the patients had RBD. Poor sleepers were more likely to have left-side predominant motor symptoms. Compared with good sleepers, poor sleepers, particularly female patients, had more burden in the aspect of anxiety and depression. RBD was associated with more nonmotor symptoms, poor sleep quality, bad performance in cognition orientation domain, anxiety, depression, presence of minor hallucination, and poor life quality.Conclusion: Sleep disturbances are common in drug-naïve PD and require wide attention. Motor symptom laterality and gender difference in mood are associated with sleep quality. Depression, anxiety, and RBD are highly related to sleep disturbance. RBD has many comorbidities, which can influence the cognitive function and life quality of the patients.Keywords: Parkinson’s disease, drug naïve, sleep disturbance, REM sleep behavior disorder, depression, anxiety

Wenhao Ding,1,&ast; Yanyan Li,1,&ast; Yichun Bai,1 Yuhong Li,2 Lei Wang,3 Yongbin Wang1 1Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, People’s Republic of China; 2National Center for Tuberculosis Control and Prevention, China Center for Disease Control and Prevention, Beijing, People’s Republic of China; 3Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universität Zu Berlin and Berlin Institute of Health, Berlin, Germany&ast;These authors contributed equally to this workCorrespondence: Yongbin WangDepartment of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 453000, People’s Republic of ChinaEmail wybwho@163.comObjective: COVID-19 may have a demonstrable influence on disease patterns. However, it remained unknown how tuberculosis (TB) epidemics are impacted by the COVID-19 outbreak. The purposes of this study are to evaluate the impacts of the COVID-19 outbreak on the decreases in the TB case notifications and to forecast the epidemiological trends in China.Methods: The monthly TB incidents from January 2005 to December 2020 were taken. Then, we investigated the causal impacts of the COVID-19 pandemic on the TB case reductions using intervention analysis under the Bayesian structural time series (BSTS) method. Next, we split the observed values into different training and testing horizons to validate the forecasting performance of the BSTS method.Results: The TB incidence was falling during 2005– 2020, with an average annual percentage change of − 3.186 (95% confidence interval [CI] − 4.083 to − 2.281), and showed a peak in March–April and a trough in January–February per year. The BSTS method assessed a monthly average reduction of 14% (95% CI 3.8% to 24%) in the TB case notifications from January–December 2020 owing to COVID-19 (probability of causal effect=99.684%, P=0.003), and this method generated a highly accurate forecast for all the testing horizons considering the small forecasting error rates and estimated a continued downward trend from 2021 to 2035 (annual percentage change =− 2.869, 95% CI − 3.056 to − 2.681).Conclusion: COVID-19 can cause medium- and longer-term consequences for the TB epidemics and the BSTS model has the potential to forecast the epidemiological trends of the TB incidence, which can be recommended as an automated application for public health policymaking in China. Considering the slow downward trend in the TB incidence, additional measures are required to accelerate the progress of the End TB Strategy.Keywords: COVID-19, tuberculosis, BSTS, ARIMA, causal impact, nowcasting and forecasting

Ruirui Zhang,1 Shanjun Gao,2 Shenghui Wang,3 Jiewen Zhang,1,3 Yingying Bai,3 Shuang He,3 Pan Zhao,3 Hongju Zhang1,3 1Department of Neurology, Henan Provincial People’s Hospital Affiliated to Henan University, Zhengzhou, Henan, People’s Republic of China; 2Microbiome Laboratory, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Neurology, Henan Provincial People’s Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Hongju ZhangDepartment of Neurology, Henan Provincial People’s Hospital Affiliated to Henan University, Zhengzhou, Henan, People’s Republic of ChinaEmail hongjuz@sina.comPurpose: To explore the characteristics of gut microbiota and its relationship between clinical manifestations in patients with type 1 narcolepsy (NT1).Patients and Methods: Scale and polysomnography were performed in 20 NT1 patients and 16 healthy controls (HC group) to evaluate the clinical characteristics of NT1. Illumina sequencing was performed on bacterial 16S ribosomal RNA gene using V3-V4 regions to compare the fecal microbiota in all subjects. Associations between clinical characteristics and gut microbiota were analyzed using partial correlation analysis.Results: Compared with the HC group, the NT1 group had a significantly higher ESS score, longer total sleep time, increased wakefulness, decreased sleep efficiency, disturbance of sleep structure, shorter mean sleep latency, and increased sleep-onset REM periods (all P < 0.05). No differences in alpha and beta diversity were observed between the two groups. In contrast, there were significant differences at the level of class, order, family, and genus (all P < 0.05). LEfSe analysis showed that the relative abundance of Klebsiella in the NT1 group was higher than that in the HC group (P < 0.05), while the relative abundance of Blautia, Barnesiellaceae, Barnesiella, Phocea, Lactococcus, Coriobacteriia, Coriobacteriales, Ruminiclostridium_5, and Bilophila were lower (all P < 0.05). Partial correlation analysis revealed that partial differential bacteria in the NT1 group were correlated with total sleep time, sleep efficiency, stage 1 sleep, arousal index, and sleep latency (all P < 0.05).Conclusion: Our data revealed differences in intestinal flora structure between NT1 patients and the normal population, thus providing a theoretical basis for future microecological therapy for narcolepsy. However, future larger sample size studies and different study designs are needed to further clarify the possible pathogenesis and potential causality of intestinal flora in NT1 patients and explore the new treatment strategies.Keywords: type 1 narcolepsy, gut microbiota, 16SrRNA, high throughput sequencing

Yang Bai,1,&ast; Fei Guan,1,&ast; Feifan Zhu,1 Chunjie Jiang,1 XiaoXiao Xu,1 Fang Zheng,2 Wenqi Liu,1 Jiahui Lei1 1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiahui LeiDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-13329722645Fax +86-27-83691246Email leijiahui@hotmail.comPurpose: Schistosoma japonicum-infected IL-33 and ST2 gene deficiency (IL-33−/− and ST2−/−, respectively) mice were used to explore the role of the IL-33/ST2 axis in liver pathology targeting regulatory T cells (Treg)/T helper 17 cells (Th17).Materials and Methods: Each mouse was infected percutaneously with 20 S. japonicum cercariae. Hepatic mass index (HMI), liver egg granulomas, hepatic fibrosis biomarkers and serum levels of alanine aminotransferase (ALT) were investigated. Treg and Th17 frequency was determined by flow cytometry. Expressions of Foxp3, ST2, TGF-β 1, IL-10, RORγt, and IL-17A were measured via quantitative real-time polymerase chain reaction (qRT-PCR). Concentrations of TGF-β 1, IL-10 and IL-17A were tested with ELISA. In vitro experiments, mRNA expressions of Foxp3, TGF-β 1, IL-10, Atg5, Beclin-1 and p62 associated with polarization of Treg by recombinant mouse IL-33 (rmIL-33) were detected by qRT-PCR.Results: An increased expression of IL-33/ST2 was shown in S. japonicum-infected mice. Deficiency of IL-33 or ST2 gene led to an aggravated liver pathology, which was evidenced by elevated hepatic granuloma volume, HMI and ALT levels and fibrosis, which was demonstrated by increased hepatic collagen deposition in the infected mice. Injection of rmIL-33 into the infected IL-33−/− mice strongly abrogated the liver pathology and fibrosis, whereas no detectable effect with injecting rmIL-33 into the infected ST2−/− mice. Furthermore, depletion of the IL-33/ST2 axis inhibited Treg, accompanied by increased Th17. rmIL-33 treatment upregulated Treg and downregulated Th17 in the infected IL-33−/− mice, while no effect in the infected ST2−/− mice. rmIL-33 led to elevated expressions of Atg5, Beclin-1 and inhibited expression of p62 in expansion of Treg.Conclusion: The IL-33/ST2 axis plays a protective role in S. japonicum infected mice, which is closely related to increasing Treg responses as well as suppressing Th17 responses. Expansion of Treg by IL-33 may be associated with its regulation of autophagy.Keywords: IL-33, ST2, liver pathology, fibrosis, Treg, Th17, autophagy

Qin Shi,1,2,&ast; Tongqiang Li,1,2,&ast; Songjiang Huang,1,2,&ast; Yaowei Bai,1,2 Yingliang Wang,1,2 Jiacheng Liu,1,2 Chen Zhou,1,2 Yang Chen,1,2 Bin Xiong1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin XiongDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, People’s Republic of ChinaEmail herr_xiong@126.comPurpose: To evaluate the effect and immune response of transcatheter arterial embolization (TAE) combined with donafenib in rabbit VX2 liver tumor model.Materials and Methods: Thirty-six New Zealand white rabbits with VX2 liver tumor were randomly divided into three groups. The LD group was treated with the emulsion of 0.5 mL lipiodol and 4 mg donafenib via hepatic arterial administration. The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The control group was treated with the equal volume of saline. Four rabbits were euthanized in each group on day 1, 3 and 7 after treatment. The tumor growth, histological markers associated with angiogenesis and immune response were assessed by imaging and histopathology. In addition, immune modulatory cytokines included interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and biochemical hepatorenal function were measured.Results: Compared to other groups, LD group achieved lower tumor growth rate, fewer metastatic lesions, and higher tumor necrosis rate on day 7 after treatment. The percentage of CD31-positive area in the LD group was significantly lower than that in the LE group on day 3 and 7 after treatment. In addition, CD8+ lymphocytes infiltration was more pronounced in LD group than in LE group on day 7 after treatment, regardless of in the tumor or adjacent liver tissue. Serum cytokines including IL-6, TNF-α and IFN-γ were strongly upregulated in the LD group on day 1 after treatment. And there was no significant difference in the hepatorenal function between LD group and LE group after treatment.Conclusion: The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer.Keywords: liver cancer, transcatheter arterial embolization, donafenib, tumor angiogenesis, immune response

Yuhan Xiao,1,&ast; Yanyan Li,1,&ast; Yuhong Li,2 Chongchong Yu,1 Yichun Bai,1 Lei Wang,3 Yongbin Wang1 1Department of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, People’s Republic of China; 2National Center for Tuberculosis Control and Prevention, China Center for Disease Control and Prevention, Beijing, People’s Republic of China; 3Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt–Universität Zu Berlin and Berlin Institute of Health, Berlin, Germany&ast;These authors contributed equally to this workCorrespondence: Yongbin WangDepartment of Epidemiology and Health Statistics, School of Public Health, Xinxiang Medical University, No. 601 Jinsui Road, Hongqi District, Xinxiang, Henan Province, 453003, People’s Republic of ChinaTel +86-373-3831646Email wybwho@163.comObjective: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS).Methods: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA).Results: The TBATS (0.27, {0,0}, -, {< 12,4>}) and SARIMA (0,1,(1,3))(0,1,1)12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May–June and November–December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=− 6.767, 95% confidence intervals: − 10.592 to − 2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years.Conclusion: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.Keywords: HFRS, hantavirus, TBATS, SARIMA, ETS, trend, seasonality, time series analysis

Luna Sun,1,2,&ast; Bin Yi,3,&ast; Xiao Pan,4,&ast; Lili Wu,1,2,&ast; Zhilei Shang,1,2,&ast; Yanpu Jia,1,2 Xiandong Tao,3 Feng Zhao,5 Weifen Xie,6 Zhuoer Sun,1,2 Yonghai Bai,4 Weizhi Liu1,2 1Lab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The Emotion & Cognition Lab, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Eastern Hepatobiliary Surgery Hospital, Shanghai; Department II of Infectious Disease, Huoshenshan Hospital, Wuhan, 430100, People’s Republic of China; 4Department of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China; 5Hongkou District of Changhai Hospital, Naval Medical University, Shanghai, 200081, People’s Republic of China; 6Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhi LiuLab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel/Fax +86-21-81871671Email 13024141970@163.comYonghai BaiDepartment of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of ChinaTel/Fax +86-21-81885057Email baiyonghai179@126.comBackground: The outbreak of COVID-19 has developed into a pandemic. Data are required that specifically address the psychological consequences in COVID-19 confirmed patients. This study mainly aimed to examine posttraumatic stress disorder (PTSD) symptoms and sleep quality among COVID-19 confirmed patients during hospitalization.Methods: An observational study was conducted in two designated hospitals in Wuhan, China. Data were collected from 190 patients hospitalized with laboratory-confirmed COVID-19 infection between February 10, 2020 and March 13, 2020.Results: The mean age of the 190 confirmed patients was 55.7 years (SD = 13.7), of which 96 (50.5%) were female and 88 (46.3%) had family members or acquaintances infected with COVID-19. Lymphocytopenia was presented in 62 (32.6%) patients and 25 (13.2%) patients showed oxygen desaturation. The prevalence of high PTSD symptoms was 22.6% among the 190 patients. The median time from symptom onset to first medical visit and hospitalization was 2 days (IQR, 1– 5) and 16 days (IQR, 10– 27), respectively. Patients’ PTSD symptoms were positively related to the time from symptom onset to first medical visit (r = 0.156, p < 0.05) and hospitalization (r = 0.181, p < 0.01). There were significant correlations between sleep quality and PTSD symptoms (r = 0.312– 0.547, p < 0.01).Conclusion: The prevalence of high PTSD symptoms was 22.6% among hospitalized COVID-19 patients. Early diagnosis and treatment of COVID-19 symptoms are beneficial to infected patients both physically and psychologically. With the recovery of physical symptoms, psychological intervention is desired to promote the trauma recovery in COVID-19 patients.Keywords: COVID-19, patients, psychological, PTSD, sleep quality