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Qi Shi,1,* Tingting Hu,2,* Lixia Xu,2,* Jiayuanyuan Fu,1 Yehong Fang,1 Yu Lan,1 Weijia Fan,2 Qiaoli Wu,2 Xiaoguang Tong,1– 3 Hua Yan1– 3 1Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, 300350, People’s Republic of China; 3Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, 300350, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Yan, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Email yanh2023@tmu.edu.cnBackground: Acute lung injury (ALI) is a serious yet common complication in patients with traumatic brain injury (TBI), often associated with poor prognosis. The development of TBI-induced ALI is closely associated with excessive oxidative stress and NLRP3 inflammasome activation. Fingolimod, an immunomodulatory agent, has been reported to attenuate inflammatory responses, restore blood-brain barrier integrity, reduce cerebral edema, and mitigate associated neurological deficits.Objective: This study aimed to investigate the mechanistic role of NLRP3 inflammasome activation in TBI-induced ALI and to evaluate the therapeutic potential of fingolimod in targeting this inflammatory pathway.Results: A rat TBI model was established using the classical free-fall method, and animals were treated with fingolimod (0.5 or 1 mg/kg) daily for three days. The TBI model rats presented with clear signs of histopathological pulmonary damage, an increase in the permeability of capillaries in the lung, and pulmonary edema that coincided with significantly increased NLRP3, caspase-1, and ASC expression in lung tissue samples. This overexpression of NLRP3 inflammasome machinery resulted in the release of IL-1β. Fingolimod treatment, however, reversed all of these effects such that it suppressed NLRP3 activity and normalized levels of IL-1β, leading to the alleviation of inflammation. In line with these results, LPS and nigericin (NLRP3 agonist)-treated NR8383 cells treated using fingolimod exhibited reductions in reactive oxygen species production and NLRP3 inflammasome activation.Conclusion: These findings suggest that NLRP3 inflammasome activation and oxidative stress are key mediators of TBI-induced ALI. Fingolimod exerts protective effects against this condition by inhibiting NLRP3 inflammasome activation, highlighting its potential as a therapeutic agent for TBI-associated pulmonary complications. Keywords: traumatic brain injury, acute lung injury, fingolimod, NLRP3 inflammasomes, reactive oxygen species

Yiyun Xu,1,* Jie Li,1,* Yu Qiu,1 Fuyue Wu,2 Zhuowei Xue,1 Bin Liu,1 Hongjie Fan,1 Yuedi Zhou,1 Qingkai Wu1 1Department of Obstetrics and Gynecology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Organoid Regeneration Research Center, ReMed Regenerative Medicine Clinical Application Institute, Shanghai, 201114, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingkai Wu; Yuedi Zhou, Email wuqingkai@sjtu.edu.cn; zhouyuedi@126.comBackground: Scar formation following large-area vaginal defects post-vaginoplasty is a major clinical challenge. Compared to skin scars, vaginal scars can lead to pain during intercourse and urinary difficulties, severely impacting quality of life. Small extracellular vesicles (sEVs) encapsulate diverse bioactive components, making them potential therapeutic agents. Designing functional scaffolds that incorporate sEVs is a promising approach for scarless vaginal defect repair.Methods: sEVs-loaded scaffolds were developed through electrostatic interactions between negatively charged sEVs secreted by urine-derived stem cells (USC-sEVs) and positively charged human acellular amniotic membranes. The efficacy of sEVs-loaded scaffolds in the treatment of vaginal defects in rabbits was assessed by histological analysis. Immunofluorescence staining, Western blot, qRT-PCR and collagen gel contraction analyses were conducted to evaluate the antifibrotic effects of USC-sEVs. RNA sequencing was employed to elucidate the underlying mechanisms involved. LC‒MS/MS analysis was used to identify candidate upstream proteins in USC-sEVs.Results: In vivo experiments demonstrated that the sEVs-loaded scaffolds promoted scarless healing of vaginal defects in rabbits by modulating collagen deposition, reducing fibrosis, and diminishing inflammation. In vitro experiments revealed that USC-sEVs significantly inhibited the proliferation, collagen production, and activation of fibroblasts with a fibrotic phenotype, indicating the antifibrotic properties of USC-sEVs. Transcriptome and Western blot analyses revealed that USC-sEVs treatment inhibited fibrosis by downregulating the TGF-β and p38 MAPK signaling pathways. LC‒MS/MS analysis identified 2653 proteins encapsulated in USC-sEVs. Western blot analysis revealed that decorin, an inhibitor of the TGF-β signaling pathway, and DUSP3, a negative regulator of p38 phosphorylation, were enriched in USC-sEVs and could be transferred to fibroblasts.Conclusion: USC-sEVs inhibited fibrosis and promoted scarless healing by delivering decorin and DUSP3 proteins, which regulate the TGF-β and p38 MAPK signaling pathways, respectively. This study highlights the potential of sEVs-loaded scaffolds as a promising strategy for scarless vaginal repair following vaginoplasty, offering a novel approach for regenerative medicine with significant translational potential for clinical application. Keywords: small extracellular vesicles, urine-derived stem cells, vaginal defects, scarless repair, anti-fibrosis

Chenyao Lin,1 Hui Zhang,2 Qiaoping Wu,1 Xuedan Qiu,1 Qingcao Li,1 Guangliang Wu3 1Department of Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, People’s Republic of China; 3Department of Clinical Pharmacy, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Qingcao Li, Department of Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, 57 Xingning Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel +86 139-8931-6035, Email lqc_lab@163.com Guangliang Wu, Department of Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, 57 Xingning Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel +86 137-7709-1293, Email Lwuguang0313@163.comBackground: The emergence of multidrug-resistant bacteria limits antibiotic efficacy, making accurate antimicrobial susceptibility testing (AST) essential for clinical decisions. Broth microdilution (BMD) is the gold standard but is impractical for routine application. Current automated AST systems improve efficiency but face accuracy or operational challenges, highlighting the need for reliable and user-friendly solutions.Objective: This study aims to evaluate the performance of a novel automated AST system (AutoMic-i600) based on the BMD method for AST of common clinical bacteria.Methods: A total of 229 clinical isolates (150 Gram-negative and 79 Gram-positive) were prospectively collected from microbiology laboratory between June 2023 and August 2023. We reported the comparison of the AutoMic-i600 and Vitek 2 systems for routine antibiotics, and also validated the detection performance of AutoMic-i600 for novel antibiotics, based on the BMD method.Results: The overall essential agreement (EA) and categorical agreement (CA) between AutoMic-i600 and BMD were 93.2% and 93.5% for Gram-negative bacteria and 98.5% and 97.8% for Gram-positive bacteria, respectively. The overall EA and CA between Vitek 2 and BMD were 92.6% and 93.5% for Gram-negative bacteria and 97.9% and 97.4% for Gram-positive bacteria. Importantly, for drug-resistant bacteria, AutoMic-i600 demonstrated a higher overall agreement than Vitek 2 (EA: 98.1% vs 94.8%, CA: 97.5% vs 92.0%), especially in Gram-negative bacteria (EA: 97.7% vs 93.5%, CA: 97.7% vs 89.3%). The VME rate for Gram-negative bacteria using AutoMic-i600 was significantly lower than that of Vitek 2 (1.0% vs 2.9%). Novel antibiotics detected by AutoMic-i600 exhibited EA and CA rates exceeding 90.0%.Conclusion: Based on these findings, we recommend that the AutoMic-i600 system could be a new option for routine AST testing in a clinical setting. Particularly for drug-resistant bacteria and novel antibiotics, detection with AutoMic-i600 may be more reliable, which could further contribute to the prevention and treatment of drug-resistant bacteria.Keywords: antibiotic susceptibility testing, drug-resistant bacteria, AutoMic-i600 system, automate

Yujia Fu,1,2,&ast; Jingjie Wu,3,&ast; Zhiting Guo,4 Yajun Shi,1 Binyu Zhao,1,2 Jianing Yu,1,2 Dandan Chen,3 Qiwei Wu,1,2 Erxu Xue,3 Haoyang Du,3 Huafang Zhang,1 Jing Shao1,2 1Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of China; 2School of Nursing and Institute of Nursing Research, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU), Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shao, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email 11318202@zju.edu.cnPurpose: This study aims to identify self-management behavior profiles in multimorbid patients, and explore how workload, capacity, and their interactions influence these profiles.Patients and Methods: A sequential explanatory mixed-methods design was employed. In the quantitative phase (August 2022 to May 2023), data were collected from 1,920 multimorbid patients across nine healthcare facilities in Zhejiang Province. Latent Profile Analysis (LPA) was used to identify distinct self-management behavior profiles. Multinomial logistic regression was then used to assess the influence of workload and capacity dimensions (independent variables in Model 1), as well as their interaction (independent variables in Model 2), on these profiles (dependent variables in two models). The qualitative phase (May to August 2023) included semi-structured interviews with 16 participants, and the Giorgi analysis method was used for data categorization and coding.Results: Quantitative analysis revealed three self-management behavior profiles: Symptom-driven Profile (8.0%), Passive-engagement Profile (29.5%), and Active-cooperation Profile (62.5%). Compared to the Active-cooperation Profile, both the Symptom-driven and Passive-engagement Profiles were associated with a higher workload (OR > 1, P < 0.05) and lower capacity (OR < 1, P < 0.05). An interaction of the overall workload and capacity showed a synergistic effect in the Passive-engagement Profile (OR = 1.08, 95% CI = 1.03– 1.13, P < 0.05). Qualitative analysis identified six workload themes, and related coping strategies of three self-management behavior profiles. The integrated results highlighted distinct characteristics: Symptom-driven Profile patients exhibited reactive behaviors with limited health awareness, Passive-engagement Profile patients reduced engagement once symptoms stabilized, while Active-cooperation Profile patients proactively managed their conditions.Conclusion: Identifying three distinct self-management behavior profiles and their relationship with workload and capacity provides valuable insights into multimorbid patients’ experiences, emphasizing the need for tailored interventions targeting workload and capacity to improve health outcomes.Keywords: multimorbidity, self-management, workload, capacity, interaction, mixed-methods study

Yong Chen,1,&ast; Qichao Cui,2,&ast; Jin Cao,1 Qiuyue Wu,1 Peixuan Lu,1 Gang Li,3 Ning Sun1 1Department of Clinical Laboratory Science, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Ultrasound Diagnosis, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Li; Ning Sun, Email nju8icu@126.com; steamsn@163.comObjective: This study investigated the distribution and changes in pancreatic infections among patients with acute pancreatitis (AP) from 2019 to 2023, while exploring the impact of multidrug-resistant bacterial infections on the prognosis of patients with poor outcomes.Methods: This study included patients diagnosed with SAP between 2019 and 2023 and collected the demographic and clinical characteristics of all participants. Based on routine clinical microbiological culture results, the distribution and drug resistance of pathogens associated with pancreatic infections were analyzed. Multivariable logistic regression was used to evaluate the association between multidrug-resistant organism (MDRO) infection and poor prognosis.Results: A total of 1586 pancreatic fluid specimens were analyzed and collected from 843 patients diagnosed with AP. The positive rate of the culture results was 81% (1280/1586), with the predominant pathogens identified as Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, and Acinetobacter baumannii complex. Of the 843 patients, 756 met the criteria, and the proportion of MDROs in pancreatic infections was 87.57% (662/756). Multivariate logistic regression analysis revealed that septic shock, acute kidney injury, and tracheostomy were associated with a poor prognosis, whereas ICU length of stay, infected pancreatic necrosis, and tracheostomy were associated with multidrug-resistant bacterial infections in patients with severe or critical AP.Conclusion: The proportion of MDRO infections in patients with severe or critical AP was notably high, primarily involving multidrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Septic shock, acute kidney injury, and tracheostomy have been identified as independent risk factors of poor prognosis in patients with severe or critical AP.Keywords: severe acute pancreatitis, pancreatic infection, microbiological profiles, multidrug-resistant organism, risk factor

Lu Wang, Huijuan Liu, Guohui Chen, Qinglu Wu, Songrui Xu, Qichao Zhou, Yadong Zhao, Qiaorong Wang, Ting Yan, Xiaolong Cheng Key Laboratory of Cellular Physiology of the Ministry of Education, & Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi Province, 030001, People’s Republic of ChinaCorrespondence: Ting Yan; Xiaolong Cheng, Email enntei@hotmail.com; chengxl@sxmu.edu.cnAbstract: Exosomes are vesicles ranging from 30 to 100 nanometers in size that show great potential as carriers for therapeutic uses and drug delivery. Enriching a specific set of miRNAs in exosomes emphasizes the existence of particular sorting mechanisms that manage the targeted cargo packaging. The molecular mechanism for miRNA sorting has not been understood. It is crucial to understand the mechanism of exosome encapsulation to develop its therapeutic potential. In this review, we will explore the particular processes through which exosomes naturally encapsulate miRNA, as well as discuss the effect on tumors after encapsulation of miRNAs. We also summarize the effects of targeted drug delivery using genetic engineering and chemical methods to modify exosome-encapsulated miRNA. Finally, gaining insight into how exosome cargo is sorted could be applied in clinical settings for precise drug delivery and to hinder the progression of diseases.Keywords: exosomes miRNA, sorting mechanism, tumor microenvironment, cancer

Peng Liu,1,2 Qi Wu,3 Mengjie Li2 1School of Graduate, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Cangzhou Fifth Hospital (People’s Hospital of Qingxian), Cangzhou, People’s Republic of China; 3Department of Respiratory Medicine, General Hospital of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Qi Wu, Department of Respiratory Medicine, General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China, Email wuqitjykdxzyy@163.comPurpose: This retrospective study aimed to evaluate the efficacy of ulinastatin in the treatment of COVID-19 patients compared to conventional therapy.Patients and Methods: A total of 437 COVID-19 patients admitted to the Respiratory Oncology Department of our hospital between December 31, 2022, and July 8, 2023, were included in the study. Patients were classified into the observation group (n=62) receiving ulinastatin in addition to standard treatment and the control group (n=347) receiving standard treatment only. Clinical information, laboratory results, and treatment outcomes were collected and analyzed.Results: The observation group showed an improvement in lymphocyte count compared to the control group. The clinical improvement rate in patients receiving ulinastatin for 7 days or longer was 92.1%, significantly higher than that of patients treated for less than 7 days (62.5%) and those receiving standard treatment (71.0%). No significant difference in total length of hospitalization was observed between the two groups, and no related adverse events occurred in either group.Conclusion: Ulinastatin treatment improves lymphocyte counts in severe COVID-19 patients, and the clinical improvement rate is significantly higher with treatment duration of 7 days or longer. Larger-scale randomized controlled trials are warranted to further explore the role of ulinastatin in the management of COVID-19.Keywords: COVID-19, ulinastatin, severe cases, clinical improvement, radiographic findings

Qiao Wu,1 Wei Sun,1 Jiaojiao Liu,2 Peiwen Zhang2 1Department of Psychiatry, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang City, Sichuan Province, People’s Republic of China; 2Research Center of Educational Neuroscience, School of Educational Science, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People’s Republic of ChinaCorrespondence: Qiao Wu; Peiwen Zhang, Email bridgeqiao@foxmail.com; zhangpeiwen118@sina.comBackground: Major depressive disorder (MDD) poses a significant treatment challenge, with some patients unresponsive to conventional therapies. Electroconvulsive therapy (ECT) can be effective but its mechanisms are not fully understood. This study employs functional Near-Infrared Spectroscopy (fNIRS) to explore the neurobiological changes induced by ECT in A MDD patient, aiming to shed light on its therapeutic effects.Purpose: This study employs fNIRS to assess differences between MDD patient and controls, and examines changes in cerebral hemodynamics and brain network nodes post-ECT to elucidate treatment mechanisms.Methods: 26 age and gender-matched controls and one MDD male patient underwent fNIRS during a verbal fluency task. The patient received ECT, with dynamic evaluation of beta, integral, and centroid values in regions of interest (ROIs) post-treatment. Resting-state fNIRS and functional connectivity assessments were also conducted post-ECT.Results: MDD patient exhibited significantly lower hemodynamic metrics and functional connectivity compared to controls at baseline. Post-ECT, dynamic changes in these metrics were observed, trending towards normalization and showing no significant differences from controls.Conclusion: ECT modifies cerebral hemodynamics and functional connectivity in depressive patients, as evidenced by fNIRS metrics. This study underscores the utility of fNIRS for objective neurobiological monitoring in ECT treatment.Keywords: functional near-infrared spectroscopy, cerebral hemodynamics, major depressive disorder, electroconvulsive therapy

Yaxin Guo,1,&ast; Jun Liao,1,&ast; Shunian Li,1 Yiyan Shang,2 Yunxia Wang,2 Qingxia Wu,3 Yaping Wu,1 Meiyun Wang,1 Fengshan Yan,1 Hongna Tan1 1Department of Radiology, People’s Hospital of Zhengzhou University & Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Radiology, People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 3Beijing United Imaging Research Institute of Intelligent Imaging & United Imaging Intelligence (Beijing) Co., Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongna Tan; Fengshan Yan, Department of Radiology, People’s Hospital of Zhengzhou University & Henan Provincial People’s Hospital, Weiwu Road, Zhengzhou City, 450003, People’s Republic of China, Tel +86-13526766042 ; +86-18637134815, Email natan2000@126.com; mountyan857@163.comBackground: Histological grade is an acknowledged prognostic factor for breast cancer, essential for determining clinical treatment strategies and prognosis assessment. Our study aims to establish intra- and peritumoral radiomics models using T2WI and DWI MR sequences for predicting the histological grade of breast cancer.Methods: 700 breast cancer cases who had MRI scans before surgery were included. The intratumoral region (ITR) of interest was manually delineated, while the peritumoral region (PTR-3 mm) was automatically obtained by expanding the ITR by 3 mm. Radiomics features were extracted using the intra- and peritumoral images from T2WI and DWI sequences on breast MRI. Then, the key features with the strongest predictivity of histological grade were selected. Finally, 9 predictive radiomics models were established based on T2WI-ITR, T2WI-3mmPTR, DWI-ITR, DWI-3mmPTR, T2WI-ITR + 3mmPTR, DWI-ITR + 3mmPTR, (T2WI + DWI)-ITR, (T2WI + DWI)-3mmPTR and (T2WI + DWI)-ITR + 3mmPTR.Results: The (T2WI + DWI)-ITR + 3mmPTR contained 13 DWI features which included a shape feature, a texture feature, and 11 filtered features, as well as 10 T2WI features, all of which were filtered features. Among the 9 models, the combined models showed better performance than the single models in both the training and test sets, especially for the (T2WI + DWI)-ITR + 3mmPTR radiomics model. The (T2WI + DWI)-ITR + 3mmPTR radiomics model achieved a sensitivity, specificity, accuracy, and AUC of 80.4%, 72.4%, 75.0%, and 0.860 in the training set, and 68.9%, 70.5%, 70.0%, and 0.781 in the test set. Decision curve analysis (DCA) showed that the (T2WI + DWI)-ITR + 3mmPTR model had the greatest net clinical benefit compared to the other models.Conclusion: The intra- and peritumoral radiomics methodologies using T2WI and DWI MR sequences could be utilized to assess histological grade for breast cancer, particularly with the (T2WI + DWI)-ITR + 3mmPTR radiomics model demonstrating significant potential for clinical application.Keywords: breast cancer, histological grade, MRI, T2WI, DWI, radiomics

Peng Yuan,1,&ast; Zhong-Hua Ma,2,&ast; Yan Yan,1,&ast; Shi-Jie Li,2 Jing Wang,2 Qi Wu1 1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Endoscopy, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Endoscopy, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Wu, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Endoscopy, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China, Email wuqi1973@126.comBackground: A full examination of gastrointestinal tract is an essential prerequisite for effectively detecting gastrointestinal lesions. However, there is a lack of efficient tools to analyze and recognize gastric anatomy locations, preventing the complete portrayal of entire stomach. This study aimed to evaluate the effectiveness of artificial intelligence in identifying gastric anatomy sites by analyzing esophagogastroduodenoscopy images.Methods: Using endoscopic images, we proposed a system called the Artificial Intelligence of Medicine (AIMED) through convolutional neural networks and MobileNetV3-large. The performance of artificial intelligence in the recognition of anatomic sites in esophagogastroduodenoscopy images was evaluated by considering many cases. Primary outcomes included diagnostic accuracy, sensitivity, and specificity.Results: A total of 160,308 images from 27 categories of the upper endoscopy anatomy classification were included in this retrospective research. As a test group, 16031 esophagogastroduodenoscopy images with 27 categories were used to evaluate AIMED’s performance in identifying gastric anatomy sites. The convolutional neural network’s accuracy, sensitivity, and specificity were determined to be 99.40%, 91.85%, and 99.69%, respectively.Conclusion: The AIMED system achieved high accuracy with regard to recognizing gastric anatomy sites, and it could assist the operator in enhancing the quality control of the used endoscope. Moreover, it could contribute to a more standardized endoscopic performance. Overall, our findings prove that artificial-intelligence-based systems can be indispensable to the endoscopic revolution (Clinical trial registration number: NCT04384575 (12/05/2020)).Keywords: artificial intelligence, convolutional neural network, esophagogastroduodenoscopy, quality control

Yucheng Wang,1,2,&ast; Jitian Weng,3,&ast; Qing Wu,4 Jiamin Wen,1,5 Qiong Gao,1,2 Wei Lu,1 Xiaohua Tao,1 Yi Tang1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4Center for Reproductive Medicine, Department of Gynecology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Dermatology, People’s Hospital of Tiantai County, Taizhou, Zhejiang, 318000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Tang, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 13968076453, Fax +86-0571-85335800, Email tangyi@hmc.edu.cnObjective: This study aimed to investigate the infection rate, types of human papillomavirus (HPV), and the relationship between HPV types and host factors in Zhejiang and lay a foundation for developing a prophylactic HPV vaccine.Methods: A retrospective analysis of the genotyping results of 27 hPV types using exfoliated cells from the cervix, vulva, perianal region, or oral mucosa of 28206 females, and exfoliated cells from the penis, perianal region or oral mucosa of 2923 male patients undergoing treatment between January 2016 and December 2021 at Zhejiang Provincial People’s Hospital was performed.Results: In females, the overall positive rate was 30.26%. The top five HPV types were HPV52, 58, 16, 6, and 53. In males, the overall positive rate was 31.85%. The top five HPV types were HPV6, 11, 16, 52, and 43. About 90.48% of patients with CINII+ were HR-HPV+. HPV33, 16 were the top two HPV types that increased CINII+ risks.Conclusion: Currently, the bivalent (HPV16, 18), quadrivalent (HPV6, 11, 16, 18), and 9-valent (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) HPV vaccines are marketed. Of these, the 9-valent HPV vaccines are more suitable for people in the Zhejiang province; however, it is still insufficient. Therefore, the 11-, 14-, and 15-valent vaccines being developed and marketed include more genotypes, and their outcomes are worth anticipating.Keywords: human papillomavirus, genotype, cervical cancer, vaccine

Yurong Ou, Ningqi Wu, Lishan Shu, Yang Zhao, Yunfang Bao, Qiong Wu Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of ChinaCorrespondence: Qiong Wu, Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, 287, Changhuai Road, Bengbu, Anhui Province, People’s Republic of China, Tel +86-18607490054, Email wuqiong@bbmc.edu.cnBackground: Existing research shows inducing ferroptosis can improve the effectiveness of tumor treatment. Glutathione peroxidase 4 (GPX4) is a ferroptosis inhibitor. Solute carrier family 7, membrane 11 (SLC7A11) plays a key role in glutathione homeostasis, which is important for protecting cells from oxidative stress. β-catenin is the key protein the Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the expression of SLC7A11 and GPX4 in colorectal cancer (CRC) and their relationship with β-catenin and to analyze the association of these two factors with several clinicopathological features and patient survival.Methods: This study retrospectively collected paraffin-embedded tissue samples from 120 CRC patients, who received surgical resection between 2017 and 2018. We examined the patterns of expression of SLC7A11, GPX4 and β-catenin by using immunohistochemistry. Analyzing the relationships between SLC7A11, GPX4, β-catenin and clinical pathological parameters and their relationships with overall survival (OS).Results: Expression of SLC7A11 and GPX4 were high expression in 60.83% and 64.17% among the patients, respectively, and were higher than those in normal tissue. SLC7A11, GPX4 and β-catenin were positively correlated with each other (P< 0.05). Expression of SLC7A11 and GPX4 significantly correlates with tumor stage and lymph node metastasis (P < 0.05). The β-catenin was related to lymph node metastasis, TNM stage and tumor grade. Kaplan–Meier analysis showed that patient’s OS in the SLC7A11 and GPX4 were reduced (P< 0.05). Univariate and multivariate analyses showed that SLC7A11 and GPX4 were independent risk factors for CRC prognosis.Conclusion: SLC7A11 and GPX4 overexpression is associated with β-catenin and poor prognosis and may be important for predicting CRC invasion, metastasis, and prognosis.Keywords: colorectal cancer, SLC7A11, GPX4, β-catenin, prognosis

Wei Song,1,2,&ast; Yaoyang Li,1,&ast; Yifan Jia,1 Lingling Xu,3 Lin Kang,4 Yunshuang Yang,5 Shuyu Wang,1 Qian Zhang,1 Qunli Wu1 1Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Institute of Clinical Medicine, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Department of Geriatric, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 5Department of Preventive Medicine, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Zhang; Qunli Wu, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Email zhangqian1@pumch.cn; chinlie@163.comPurpose: The axon guidance factors and Rho/ROCK pathway play crucial roles in axon protection and nerve repair and has been implicated in the development of diabetic peripheral neuropathy (DPN). This study investigates the protective effects of quercetin against DPN, focusing on axon guidance factors and Rho/ROCK pathway.Methods: DPN was induced by intraperitoneal injection of streptozotocin (STZ) to Sprague-Dawley rats. The DPN model rats were allocated into three groups and administered quercetin at two different doses (30 mg/kg/day and 60 mg/kg/day) or a placebo. Concurrently, healthy rats were divided into two groups and administered either a placebo or quercetin (60 mg/kg/day). Administration was initiated 8 weeks post-STZ injection and continued for a duration of six weeks. To assess quercetin’s neuroprotective effects, biochemical analyses, neurological function tests (mechanical threshold, thermal response latency, motor nerve conduction velocity), and morphological assessments via transmission electron microscopy were conducted. Immunofluorescence and immunohistochemical assays were performed on sciatic nerve tissue and high glucose-induced RSC96 rat Schwann cells to explore quercetin’s pharmacological effects on DPN.Results: Quercetin exhibited neuroprotective effects on both DPN rats and RSC96 cells exposed to high-glucose. A six-week administration of quercetin at both doses significantly improved the peripheral neurological functions and alleviated the pathological changes in sciatic nerve of DPN rats (P< 0.05). Mechanistically, quercetin markedly upregulated the expressions of axonal growth factors, Slit-2 and Netrin-1 in vivo and in vitro (P< 0.05), while inhibiting the aberrant activation of Rho/ROCK signaling pathway in the sciatic nerve of DPN rats.Conclusion: Our findings suggest that quercetin improves DPN through a novel mechanism, indicating its potential as a therapeutic agent for DPN therapy. Keywords: quercetin, diabetic peripheral neuropathy, Rho/ROCK pathway, axon guidance factor, Netrin-1, Slit-2

Qi Wu,1,&ast; Kexin Liu,2,&ast; Ruijuan Hou,1 Xingxing Wu,3 Xiaoyu Ruan,4 Mao Wang,5 Zhiting Sun,6 Lingchang Meng,6 Guoliang Dai,7 Changyin Li,7 Jing Wu,1,6 Genglin Mu6 1Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Gastroenterology, The 981th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Chengde, Hebei, 067000, People’s Republic of China; 3Department of Gastroenterology, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, 450053, People’s Republic of China; 4Internal Medicine Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 5Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 6Institute of Chinese Medicine of Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 7Clinical Pharmacology Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wu, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Institute of Chinese Medicine of Nanjing University, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email wujing@njucm.edu.cnPurpose: Inflammatory bowel disease (IBD) is a serious disease that affects the metabolism and inflammatory responses of human beings. From the perspective of traditional Chinese medicine, damp-heat syndrome is one of the main syndromes of IBD. Rhizoma Paridis, also known as the root of Paris polyphylla, a well-known herbal medicine used in China, is used to treat IBD with damp-heat syndrome (IBD-DH). However, uncertainty still exists regarding the underlying mechanisms and the impact of Rhizoma Paridis on IBD-DH.Methods: The rats in the model (DAT) and medication administration (Rhizoma Paridis total saponins (RPTS) and Pennogenin (PN)) groups were given a high temperature and high humidity environment, high fat and high sugar diet combined with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish the model of experimental colitis of damp-heat type, and the normal control group (RNC) rats were given a normal diet at normal temperature and humidity. Damp-heat control group (DNC) was set with the same condition as DAT without TNBS. Hematoxylin-Eosin (HE) staining was used to observe the histopathological morphology of the rat colorectum. The expression of the metabolism-related genes (Phospholipase A2 (sPLA2, cPLA2), and phosphatidylethanolamine N-methyltransferase (PEMT)) was assessed by using real-time quantitative PCR analysis (RT–qPCR). And the levels of the metabolism-related proteins (sPLA2, cPLA2), S100A8/9, Arg-1, and cytokines were detected by enzyme-linked immunosorbent assay (ELISA) kit. To investigate lipids and amino acids which closely associated with the IBD and IBD-DH, lipid pseudotargeted metabolomics with UHPLC-TQ/MS analysis method, as well as targeted quantitative amino acid analysis were performed.Results: Our data showed that RPTS (50 mg/kg) and PN (20 mg/kg) significantly ameliorated the severity of TNBS-induced colitis and downregulated the levels of circulating proinflammatory cytokines. Compared with RNC group, lipid pseudotargeted metabolomics demonstrated that glycerophospholipids, sphingolipids, carnitine, and glycerolipids were the four most perturbed lipid classes, and amino acids targeted metabolomics demonstrated that serine, N-acetylneuraminic acid, histidine, proline, taurine, and kynurenine changed significantly in DAT group . Correlation analyses showed tight associations between most of differential metabolites and proinflammatory cytokines. RPTS and PN both regulated glycerophospholipid metabolism and sphingolipid metabolism. However, both of them did not have a significant effect on amino acid modulation. RPTS and PN potentially regulated sPLA2, cPLA2, and PEMT.Conclusion: These results showed that RPTS (50 mg/kg) and PN (20 mg/kg) effectively alleviated rats’ colitis of damp-heat type, affected cytokines, and altered lipid metabolism without significant modulation on amino acid metabolism.Keywords: inflammatory bowel disease, lipid pseudotargeted metabolomics, amino acids targeted metabolomics, Rhizoma Paridis saponins, cytokines

Ying Wang,1,&ast; Xuelong Li,2,&ast; Yakun Gao,2 Xun Zhang,3 Yiyi Liu,3 Qing Wu1,3 1Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, Hefei Fourth People’s Hospital, Hefei, Anhui, People’s Republic of China; 2Qingdao Mental Health Center, Qingdao, Shandong, People’s Republic of China; 3School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wu, Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, 316 Huangshan Road, Hefei, 230022, People’s Republic of China, Tel +86-13856919530, Email wuqinghf@163.comPurpose: The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD.Patients and Methods: A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital’s electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings.Results: The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P< 0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P< 0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049− 39.21), BMI (OR=1.398, 95% CI=1.306− 1.497), triglycerides (OR=1.456, 95% CI=1.036− 2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110− 0.672) were risk factors for NAFLD (all P< 0.05).Conclusion: Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.Keywords: China, comorbidity, Psychiatry

Yidan Xu,1,&ast; Lu Zhang,1,&ast; Zhiyang Chen,1 Xiaonan Sun,1 Mengdan Zhao,1 Qirui Wu,2 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 81 Meishan Road, Hefei, Anhui, People’s Republic of China, Tel +86-13965029739, Email haojiqing@ahmu.edu.cnPurpose: This study aims to explore the association of inflammatory markers such as the Systemic Immune-Inflammatory Index (SII) and LANR with the comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer.Patients and Methods: A cross-sectional analysis was conducted on the clinical data of 309 patients with COPD only and 193 patients with COPD and lung cancer who attended the First Affiliated Hospital of Anhui Medical University. Additionally, we examined autonomous risk factors that contribute to the simultaneous development of COPD and lung cancer through univariate and multivariate logistic regression analyses. This analysis resulted in the development of a nomogram model for visual representation. The effectiveness of the model was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and clinical decision analysis (DCA) curve, with internal validation conducted via repeated sampling methods.Results: Multivariate analysis of clinical characteristics and inflammatory markers showed that smoking history of > 60 pack-years, hemoptysis, emphysema, WBC count > 5.53 (× 10^9/L), SII > 629.285, and LANR < 11.39 were significantly associated with the comorbidity of COPD and lung cancer. These factors were subsequently integrated into the nomogram model. The AUC of the model stood at 0.849 (95% CI: 0.815– 0.882), demonstrating a notable improvement over the COPD-LUCSS scoring system (AUC: 0.716, 95% CI: 0.671– 0.761). The DCA curve indicated a notable clinical advantage provided by the model. Additionally, patients with stage IV tumors exhibited elevated SII levels and reduced LANR levels compared to earlier stages, indicating potential prognostic significance for both markers.Conclusion: Increased levels of the inflammatory markers SII and LANR are associated with the risk of comorbidity of COPD and lung cancer.Keywords: lung cancer, inflammation, systemic immune-inflammation index, nomogram, LANR, chronic obstructive pulmonary disease

Shanshan Li,1,2 Le Zhang,3 Boyi Yang,3 Yi Huang,3 Yuqi Guan,3 Nanbo Huang,1 Yingnan Wu,1 Wenshuo Wang,1 Qing Wang,1 Haochen Cai,1 Yong Sun,1 Zijun Xu,1 Qin Wu1,2 1Medical College, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 2Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Qin Wu, Medical College, Jiangsu Vocational College of Medicine, No. 283, South Jiefang Road, Yancheng, 224005, People’s Republic of China, Tel +86-515-88159750, Email hhwuq@163.comBackground: In elderly diabetic patients, depression is often overlooked because professional evaluation requires psychiatrists, but such specialists are lacking in the community. Therefore, we aimed to create a simple depression screening model that allows earlier detection of depressive disorders in elderly diabetic patients by community health workers.Methods: The prediction model was developed in a primary cohort that consisted of 210 patients with diabetes, and data were gathered from December 2022 to February 2023. The independent validation cohort included 99 consecutive patients from February 2023 to March 2023. Multivariable logistic regression analysis was used to develop the predictive model. We incorporated common demographic characteristics, diabetes–specific factors, family structure characteristics, the self–perceived burden scale (SPBS) score, and the family APGAR (adaptation, partnership, growth, affection, resolution) score. The performance of the nomogram was assessed with respect to its calibration (calibration curve, the Hosmer–Lemeshow test), discrimination (the area under the curve (AUC)), and clinical usefulness (Decision curve analysis (DCA)).Results: The prediction nomogram incorporated 5 crucial factors such as glucose monitoring status, exercise status, monthly income, sleep disorder status, and the SPBS score. The model demonstrated strong discrimination in the primary cohort, with an AUC of 0.839 (95% CI, 0.781– 0.897). This discriminative ability was further validated in the validation cohort, with an AUC of 0.857 (95% CI, 0.779– 0.935). Moreover, the nomogram exhibited satisfactory calibration. DCA suggested that the prediction of depression in elderly patients with diabetes mellitus was of great clinical value.Conclusion: The prediction model provides precise and user–friendly guidance for community health workers in preliminary screenings for depression among elderly patients with diabetes.Keywords: prediction model, depression, elderly, diabetes, community–based

Yanhong Liu,1 Qi Wang,1 Chuanlei Zheng,1,2 Zhengchun Huang,3 Jian Li,3 Ming Hao,1 Minghua Dong,1,2 Xiaoting Luo,2,4 Qingfeng Wu1,2 1School of Public Health & Healthcare Management, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, People’s Republic of China; 4School of General Practice Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Qingfeng Wu, Gannan Medical University, Rongjiang New District College Park, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8169713, Fax +86-797-8169600, Email wuqf2006@gmu.edu.cnPurpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures.Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City’s permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence.Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83± 7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03– 1.06), hypertension (OR=2.22, 95% CI:1.71– 2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58– 4.85), overweight (OR=1.73, 95% CI: 1.20– 2.48), high total cholesterol (OR=1.17, 95% CI:1.09– 1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00– 1.40) and serum insulin (OR=1.05, 95% CI:1.03– 1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36– 0.84) was found to be inversely related to T2DM development.Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.Keywords: type 2 diabetes mellitus, cross-sectional studies, epidemiology, influence factors

Qian Wu,1,&ast; Qing-Qing Dong,1,&ast; Si-Hui Wang,1 Yi Lu,1 Yi Shi,1 Xiao-Ling Xu,2 Wei Chen1 1ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64385700-3522, Email cwdoctor@shutcm.edu.cn Xiao-Ling Xu, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cnBackground: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects.Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study.Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression.Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis. Keywords: sepsis, rheinic acid, tanshinone IIA, exosome, hybrid nanosystem

Ke Yin,1 Qiong Wu,2 Xiaosong Gai1 1School of Psychology, Northeast Normal University, Changchun, People’s Republic of China; 2Faculty of Education, Northeast Normal University, Changchun, People’s Republic of ChinaCorrespondence: Qiong Wu, Tel +86 13504314652, Fax +86 85683180, Email wuq936@nenu.edu.cnPurpose: The purpose of this study was to examine differences between directly measured and parent-evaluated executive function in predicting children’s academic achievement and social development, and to explore the mediating roles of peer status and social competence in the effects of executive function on social behavior.Patients and Methods: The study followed 106 first-grade children in an elementary school in China for one year. Regression and mediation analyses were conducted using SPSS 26.0 and AMOS 21.0 to test the hypotheses.Results: First, in a comparison of the predictive role of directly measured and parent-evaluated executive function, directly measured executive function played a more important role in predicting academic achievement, while parent-evaluated executive function played a greater role in predicting social development. Second, parent-evaluated executive function influenced social behavior primarily through social competence and peer status, with social competence playing a more significant mediating role than peer status.Conclusion: Compared with previous studies, the results of the present study provide more direct evidence for the relationship and differences between directly measured and parent-evaluated executive function, further suggesting that they have different efficacy and predictive goals, while the present study also describes the pathways through which executive function influences social behavior: the mediating role of peer status and social competence. This suggests that, on the one hand, educators or researchers need to choose appropriate measures of executive function for their own purposes and, on the other hand, in order to promote the development of children’s social behavior, they need to focus on the development of children’s executive function, social competence and peer relationships.Keywords: peer status, social behavior, social competence, cognitive control, measurement

Jianbao Zheng,1,2,&ast; Zepeng Dong,1,&ast; Xianzhen Jin,1 Jing Li,2 Yuanwu Zou,2 Guanghong Bai,2 Qianhong Wu,2 Shenghang Xu,3 Zifeng Wang,3 Xuejun Sun,1 Dingxin Liu,3 Li Guo3 1Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Tuberculosis Prevention and Treatment Hospital in Shaanxi Province, Xi’an, 710100, People’s Republic of China; 3Center for Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianhong Wu; Li Guo, Email 15902969531@126.com; guoli35@mail.xjtu.edu.cnPurpose: This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb).Methods: We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10− 2 and 10− 4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal–Wallis test was used to analyze the differences in grouping factors at representative time points.Results: The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10− 2 and SM with bacterial suspension concentration of 10− 4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference.Conclusion: The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.Keywords: plasma-activated saline, mycobacterium tuberculosis, antibacterial effect, antibiotic sensitivity

Yan Zhang,1,&ast; Qixing Wu,2,&ast; Mingming Han,2 Chengwei Yang,2 Fang Kang,2 Juan Li,2 Chengwen Hu,1 Xia Chen1 1Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Chen; Chengwen Hu, Email chenxiaahslyy@163.com; huchengwen318@126.comObjective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China.Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications.Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P< 0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338– 12.341, P < 0.001).Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.Keywords: lumbar degenerative disease, older adults, frailty, postoperative outcome

Cheng R, Wang J, Wu Q, et al. Int J Gen Med. 2024;17:1937–1948. The authors have advised that the funding statement on page 1946 is incorrect. The correct funding statement is as follows. FundingThis study was funded by Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation under Grant No. 2023GXNSFAA026455, the Guangxi Natural Science Foundation No. 2023GXNSFAA026165, Health Commission of Guangxi Zhuang Autonomous Region Self-funded research projects (Z20210625), Youth Science Foundation of Guangxi Medical University (GXMUYSF202347) and Innovation Project of Guangxi Graduate Education (YCBZ2022085). The authors apologize for this error.

Ruoxi Cheng,1,&ast; Jie Wang,1,&ast; Qing Wu,1 Peng Peng,1 Guolin Liao,1 Xiuping Luo,1 Zhihai Liang,2 Jiean Huang,1,&ast; Mengbin Qin1,&ast; 1Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiean Huang; Mengbin Qin, Department of Gastroenterology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China, Email hjagxmu@163.com; dr.mmbin@hotmail.comPurpose: This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP).Patients and Methods: The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II–IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting.Results: In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05).Conclusion: The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.Keywords: gastrointestinal injury, acute pancreatitis, DAO, HDC, MMP8

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Meiling He,1 Chunfeng Liang,1 Yadan Pang,1 Mengjie Jiang,1 Meiying Long,2 Zhongqiang Yao,3 Xiaoting Wang,1 Ruijun Zhang,1 Qiaoyuan Wu,1 Shixiong Liang,1 Jianxu Li1 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of General Affairs, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaCorrespondence: Shixiong Liang; Jianxu Li, Tel +86 13917716605 ; +86 18878732921, Email shixliang@sina.com; lijianxu1236@163.comPurpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1.Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC).Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3– 4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1– 3 years AUROC of 78.7, 78.6, and 93.5, respectively.Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.Plain Language Summary: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti‑PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3– 4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation demonstrated good reliability.Keywords: hepatocellular carcinoma, advanced, intensity-modulated radiotherapy, antibody against programmed cell death 1, nomogram

Min Jiang,1,&ast; Hui Zhang,2,&ast; Wenjun Lu,3 Xuedan Qiu,1 Chenyao Lin,1 Rongqing Zhao,1 Qingcao Li,1 Qiaoping Wu1 1Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Intensive Care Units, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingcao Li; Qiaoping Wu, The Affiliated LiHuiLi Hospital of Ningbo University, 1111 Jiangnan Road, Ningbo, Zhejiang Province, 315040, People’s Republic of China, Tel +86-574-55835786, Fax +86-574-55835781, Email lqc_lab@163.com; lhlyywqp@163.comBackground: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP’s virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence.Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence.Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest.Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.Keywords: Klebsiella pneumoniae, capsular serotypes, virulence, MLST

Qian Chen,1,2 Chengyin Yu,1,2 Qingqing Wu,1,2 Rong Song,1,2 Ye Liu,1,2 Sheng Feng,3 Chen Yu,1,2 Jingying Jia1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Jingying Jia, Center Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road (M), Shanghai, People’s Republic of China, Tel/Fax +86-21-54030254, Email jyjia@shxh-centerlab.comPurpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80– 1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.Trial Registration: ClinicalTrials.gov NCT06083116.Keywords: henagliflozin, drug-drug interaction, hydrochlorothiazide, pharmacokinetics, tolerability, pharmacodynamics, selective sodium-glucose cotransporter 2

Zilong Yue,1,2,&ast; Yan Jin,1,3,&ast; Hui Sha,1,&ast; Qin Wu,1,&ast; Lele Li,1 Yabin Xia,1 Kaifeng Hu1 1Department of Gastrointestinal Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 2General Surgery Department, Guoyang Branch of Anhui Provincial Hospital, Bozhou, Anhui, People’s Republic of China; 3Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaifeng Hu, Department of Gastrointestinal Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, No. 2, Zheshan West Road, Anhui, 241001, People’s Republic of China, Tel +86-13655537677, Email kaifenghu76@163.comPurpose: Investigating the therapeutic efficacy of Laparoscopic Sleeve Gastrectomy (LSG) in low BMI (30– 35 kg/m2) patients with obesity, and exploring the correlation between patients’ preoperative BMI and postoperative weight loss.Methods: Comparing the weight loss, remission of comorbidities, occurrence of complications, and quality of life among the different BMI patients who underwent LSG. Analyzing the relationship between BMI and percentage of excess weight loss (%EWL) by using Spearman correlation analysis and linear regression analysis.Results: The %EWL at 12 months after the surgical procedure was (104.26± 16.41)%, (90.36± 9.98)%, and (78.30± 14.64)% for patients with Class I, II, and III obesity, respectively, P< 0.05. Spearman correlation coefficients between %EWL and BMI at 1, 3, 6, and 12 months after surgery were R=− 0.334 (P< 0.001), R=− 0.389 (P< 0.001), and R=− 0.442 (P< 0.001), R=− 0.641 (P< 0.001), respectively. The remission of hypertension, diabetes and dyslipidaemia did not differ significantly between groups (P> 0.05).Conclusion: Individuals with obesity for varying BMI can experience favorable outcomes following LSG surgery. It is advisable to consider LSG treatment for patients with Class I obesity.Keywords: laparoscopic sleeve gastrectomy, body mass index, percentage of excess weight loss

Quantong Wu,1 Fuchao Xu,2 Jie Wang,3 Ming Jiang2 1Department of Anesthesiology, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Emergency Department, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Neurosurgery department, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Ming Jiang, Department of Anesthesiology, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Gulou District, Nanjing, Jiangsu, People’s Republic of China, Email 2021122013@stu.njmu.edu.cnPurpose: To systematically evaluate the effectiveness and safety of ketamine in preventing propofol injection pain (PIP).Patients and Methods: The electronic databases including PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception until 2 August 2023. Randomized controlled trials (RCT) comparing ketamine with placebo or other interventions to alleviate PIP in adults were included. Fixed-effects or random-effects models were used to calculate pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) based on the heterogeneity of the studies included.Results: Thirteen RCTs involving 2105 patients were included. In terms of reducing the incidence of PIP, ketamine is more effective than placebo (RR = 0.43, 95% CI = [0.34, 0.55], P < 0.00001), lidocaine (RR = 0.70, 95% CI = [0.55, 0.90], P = 0.005), dexmedetomidine (RR = 0.52, 95% CI = [0.40, 0.66], P < 0.00001), and thiopental (RR = 0.25, 95% CI = [0.08, 0.83], P = 0.02). In reducing the incidence of severe PIP, ketamine is superior to placebo (RR = 0.12, 95% CI = [0.08, 0.19], P < 0.00001), and lidocaine (RR = 0.34, 95% CI = [0.21, 0.56], P < 0.0001), except dexmedetomidine (RR = 0.20, 95% CI = [0.04, 1.13], P = 0.07), and thiopental (RR = 0.33, 95% CI = [0.04, 3.10], P = 0.33). Compared with mixed injection, separate injection of ketamine and propofol showed no significant difference in the incidence of PIP (RR = 0.96, 95% CI = [0.31, 3.00], P = 0.95) and severe PIP (RR = 1.19, 95% CI = [0.07, 21.29], P = 0.90). Based solely on the reports from the studies included, subanesthetic doses of ketamine are generally safe in preventing PIP.Conclusion: A subanesthetic dose of ketamine can effectively and safely reduce the incidence of PIP and severe PIP in adults, and is more effective than lidocaine, dexmedetomidine, and thiopental.Registration: PROSPERO CRD42023455093.Keywords: ketamine, pain, injection, propofol, meta-analysis

Wenping Li,1 Ting Xu,2 Liuting Diao,2 Qishu Wu3 1Prudence College, Zhejiang Business Technology Institute, Ningbo, People’s Republic of China; 2Business School, Ningbo University, Ningbo, People’s Republic of China; 3Zhejiang Business Technology Institute, Ningbo, People’s Republic of ChinaCorrespondence: Qishu Wu, Zhejiang Business Technology Institute, Airport Road, Haishu District, Ningbo, 1988, People’s Republic of China, Email 10824010@zjbti.net.cnPurpose: Perceived discrimination among higher vocational college students is a prevalent issue in China and is linked to various mental and behavioral problems, including mobile phone addiction. Yet, the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction remain ambiguous.Methods: To address this issue, we recruited 1253 higher vocational college students to elucidate the relationship between perceived discrimination and mobile phone addiction. Participants completed a series of self-report questionnaires assessing perceived discrimination, mobile phone addiction, negative emotions, and learning burnout.Results: Our findings suggest that perceived discrimination positively influences mobile phone addiction. The negative emotions and learning burnout play mediating effects between perceived discrimination and mobile phone addiction, respectively. Notably, we observe a chain mediating role of negative emotions and learning burnout play between perceived discrimination and mobile phone addiction.Conclusion: The results of our study demonstrate that higher vocational college students who perceived stronger discrimination are inclined to exhibit heightened emotional, cognitive, and learning challenges, such as increased negative emotions and learning burnout, which contribute to more serious excessive mobile phone use. These findings elucidate the mechanisms underlying the relationship between perceived discrimination and mobile phone addiction, enriching our understanding of the underlying emotional, cognitive, and learning dynamics in higher vocational college students.Keywords: perceived discrimination, mobile phone addiction, negative emotions, learning burnout, structural equation model

Jie Liu,&ast; Xia Li,&ast; Wanli Xie, Yanting Wang, Zhenzhen Xu, Yun-Xiao Bai, Quanjun Zhou, Qingping Wu Department of Anesthesiology, Union Hospital, 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; Quanjun Zhou, Email wqp1968@126.com; quanjunzhou2023@163.comObjective: The risk factors of postoperative pulmonary complications (PPCs) have been extensively investigated in non-cardiac surgery and non-elderly adult patients undergoing cardiac surgery. However, data on elderly patients after cardiopulmonary bypass (CPB) is limited. This study aimed to evaluate the risk factors and short-term outcomes for PPCs in elderly patients undergoing CPB procedures.Patients and Methods: Data from 660 patients who underwent CPB over a six-year period at a tertiary care hospital were collected. The primary outcome encompassed the incidence of PPCs, including re-intubation, postoperative mechanical ventilation exceeding 48 hours, pulmonary infection, pleural effusion requiring thoracic drainage, and acute respiratory distress syndrome. Missing data were managed using multiple imputation. Univariate analysis and the multiple logistic regression method were utilized to ascertain independent risk factors for PPCs.Results: Among the 660 patients, PPCs were observed in 375 individuals (56.82%). Multiple logistic regression identified serum albumin levels < 40 g/L, type of surgery, CPB duration > 150 minutes, blood transfusion, and intra-aortic balloon pump use before extubation as independent risk factors for PPCs. Patients experiencing PPCs had prolonged mechanical ventilation, extended hospitalization and ICU stays, elevated postoperative mortality, and higher tracheotomy rates compared to those without PPCs.Conclusion: Elderly patients following CPB displayed a substantially high incidence of PPCs, significantly impacting their prognosis. Additionally, this study identified five prominent risk factors associated with PPCs in this population. These findings enable clinicians to better recognize patients who may benefit from perioperative prevention strategies based on these risk factors.Keywords: postoperative pulmonary complications, elderly patients, cardiopulmonary bypass, cardiac surgery

Xuning Lu,1,2 Guoju Li,1 Qin Wu,1 Wei Ni,1 Silin Pan,1 Quansheng Xing1 1Heart Center, Qingdao Women and Children’s Hospital, Shandong University, Qingdao, Shandong Province, People’s Republic of China; 2Heart Center, Dalian Municipal Women and Children’s Medical Center (Group), Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Quansheng Xing, Heart Center, Qingdao Women and Children’s Hospital, Shandong University, 217 Liaoyang West Road, Qingdao, Shandong Province, 266034, People’s Republic of China, Tel +86 136 0642 6893, Fax +86 532 8285 7650, Email xqs_qdfnet@126.comObjective: The outcomes of fetuses with isolated congenital heart disease (CHD) diagnosed prenatally have not been investigated in a population-based study in China. This population-based study aimed to evaluate the rate of voluntary termination of pregnancy after the prenatal diagnosis of isolated CHD in Qingdao, China.Methods: This was a population-based retrospective study in which data were collected from all pregnant women in Qingdao (eastern China) from August 2018 to July 2020; fetal data, maternal data and data on pregnancy outcomes were extracted from medical records regarding prenatal diagnosis of CHD. The inclusion criteria were as follows: pregnant women or their husbands who had a household registration in Qingdao and who underwent regular prenatal screening in Qingdao. The exclusion criterion was the failure to sign an informed consent form. Counseling for all parents of fetuses with CHD was provided by a multidisciplinary team of experienced pediatric cardiologists, obstetricians, geneticists, etc. According to the type and severity of CHD, the pregnancy termination rate was analyzed.Results: Among the 126,843 pregnant women, 1299 fetuses with a prenatal diagnosis of CHD were included in the study. Among the included fetuses, 1075 were diagnosed with isolated CHD, and the overall pregnancy termination rate was 22.8%. Termination rates varied according to the complexity of CHD (low complexity vs moderate complexity, P=0.000; low complexity vs high complexity, P=0.000; moderate complexity vs high complexity, P=0.000), with rates of 6.0% for low complexity, 54.2% for moderate complexity, and 99.1% for high complexity. The decision to terminate the pregnancy in cases of isolated CHD was unrelated to maternal age (P=0.091) but was related to gestational age (p=0.000).Conclusion: In Qingdao, 99.1% of parents whose fetuses were diagnosed with isolated high-complexity CHD chose to voluntarily terminate the pregnancy. The pregnancy termination rate increased with increasing complexity of prenatally diagnosed CHD.Plain Language Summary: In our study population, with the popularity of prenatal diagnosis, complex congenital heart disease will disappear, because 99.1% of parents whose fetuses were diagnosed with isolated high-complexity congenital heart disease chose voluntary pregnancy termination.Keywords: congenital heart defect, fetal echocardiography, prenatal diagnosis, termination of pregnancy

Chunkun Yang,1,&ast; Qinwei Zhu,2,&ast; Yanbo Chen,3,&ast; Kui Ji,2 Shuanghong Li,2 Qian Wu,1 Qingquan Pan,2 Jun Li1 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, People’s Republic of China; 3Department of Arrhythmia, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.Keywords: curcumin, intima, endothelial cells, vascular smooth muscle cell, cardiovascular diseases, inflammation, apoptosis

Fei Meng, Qin Wu, Wei Zhang, Shirong Hou Department of Ultrasound, Xuan Cheng City Central Hospital, Xuancheng, Anhui, People’s Republic of ChinaCorrespondence: Fei Meng, Xuan Cheng City Central Hospital, No. 117, Tonggong Road, Xuanzhou Distinct, Xuancheng, Anhui, 242000, People’s Republic of China, Tel +86-18956308225, Email Fly_MengUltrasound@163.comIntroduction: Patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) face a significant risk of hepatic fibrosis. Liver stiffness measurement (LSM) is commonly used to exclude advanced fibrosis, but its effectiveness in predicting fibrosis progression, especially in initially fibrosis-free patients, remains under-investigated. Although radiomics and machine learning (ML) models show promise in interpreting intricate data and predicting clinical outcomes, their application in assessing the fibrosis progression risk has not been fully explored. This study aimed to address this gap by developing and validating ML-based models to identify patients at risk of fibrosis progression using clinical data and multimodal radiomics features, thereby enhancing NAFLD and T2DM management.Methods: The study involved a retrospective analysis of 618 diabetic patients with NAFLD. These patients were divided into training and external validation cohorts. Based on LSM values, patients were classified into “Low-risk” and “Fibrosis-risk” groups. Radiomics features from multimodal ultrasound imaging were extracted, standardized, and utilized to develop various ML models. The models were internally validated based on these radiomics or clinical data, and the optimal model’s feature importance was analyzed using the Shapley Additive Explanations (SHAP) approach, followed by external validation.Results: Of the 618 patients, 18.1% demonstrated an LSM≥ 6.5kPa, indicating a higher risk of hepatic fibrosis. The study identified 25 significant fibrosis-related radiomics features, with the support vector machine (SVM) model demonstrating superior performance in both internal and external validations. The SHAP analysis identified five key determinants of fibrosis risk, which included three radiomics features from shear wave elastography (SWE) and two from grayscale imaging.Conclusion: This study demonstrates the utility of an SVM model based on radiomics features derived from SWE and grayscale imaging for predicting fibrosis progression in diabetic patients with NAFLD, thereby enabling timely and effective therapeutic interventions.Keywords: nonalcoholic fatty liver disease, type 2 diabetes mellitus, hepatic fibrosis, machine learning, radiomics, support vector machine

Xinmiao Hu,1– 3,&ast; Qian Wu,1,2,&ast; Qunfeng Lu,4,5,&ast; Jiangao Zhang,6 Xiaowei Yang,7 Wenjian Chen,3 Ping Wang,3 Qinglin Yu,3 Jingan Dong,3 Yan Sang8 1School of Medicine, Tong University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Nursing, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 6Nantong Visionland Eye Hospital, Jiangsu, People’s Republic of China; 7School of Medicine, Nantong University, Jiangsu, People’s Republic of China; 8Department of Nursing, Department of Computer Technology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Sang, Department of Computer Technology, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu, 226001, People’s Republic of China, Tel +86 13862915051, Email sangyan_cn@126.comPurpose: To identify the difficulties and burdens related to the experience of caring for children.Methods: A phenomenological approach was used in this qualitative study. Semi-structured and adolescents with idiopathic nephrotic syndrome (INS) in mainland China. Interviews lasting 35– 90 minutes were conducted with 13 parental caregivers of youth with INS. The Colaizzi’s analysis was used in data analysis.Results: The mean age of parental caregivers was 40.3 ± 6.1 years, and the average caregiving year of 3.2 ± 3.3 years. Most INS patients were male (69.2%), had a mean age of 7.6 ± 4.2 years. Based on the analysis of the data, five major themes emerged. These were: persistent emotional burden; neglected physical burden; overwhelming financial burden; absence of social support system and burden related to loss of normal life.Conclusion: Health professionals must develop strategies to provide stage-by-stage, targeted health education and psychological support services to parental caregivers of INS youth in China. The government must subsidize routine medications and frequent hospitalizations to minimize the financial burden on parental caregivers of INS youth. Moreover, anti-discrimination policies must be established to protect caregivers from explicit discrimination in public places.Keywords: caregiver, burden, idiopathic nephrotic syndrome, youth

Chuqian Chen,1,&ast; Qinglu Wu,2,&ast; Junfeng Zhao,3 Guoxiang Zhao,4 Xiaoming Li,5 Hongfei Du,2 Peilian Chi6,7 1Department of Medical Humanities, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, Guangdong, People’s Republic of China; 3Institute of Psychology and Behavior, Henan University, Kaifeng, Henan, People’s Republic of China; 4Department of Psychology, Henan Normal University, Xinxiang, Henan, People’s Republic of China; 5Department of Health Promotion, Education, and Behavior, University of South Carolina, Columbia, SC, USA; 6Department of Psychology, Faculty of Social Sciences, University of Macau, Macau, People’s Republic of China; 7Centre for Cognitive and Brain Sciences, University of Macau, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peilian Chi, Department of Psychology, Faculty of Social Sciences, University of Macau, Mailing: E21-3049, Macau, 999078, People’s Republic of China, Tel +853 8822-4025, Email peilianchi@um.edu.moPurpose: The study aims to understand how enacted stigma influences bereavement coping at the style (scale) level and the specific pathways at the strategy (item) level.Methods: The longitudinal data of 755 children orphaned by parental Acquired Immune Deficiency Syndrome (AIDS) in rural China were used. Grief processing and deliberate grief avoidance were measured at wave 1 (baseline) and wave 2 (one-year follow-up) to reflect bereavement coping in the contexts of being with family members, being with friends, being with community members, and being alone. Enacted stigma that measured at wave 1 was used to assess the experienced stigma of these AIDS-orphaned children. Network analyses were run following regressions.Results: Controlling for demographics and baseline-level bereavement coping, multivariate regressions revealed that enacted stigma at wave 1 significantly predicted grief processing and deliberate grief avoidance at wave 2. Network analyses showed that, for grief processing, stigma increased searching for meaning alone and with friends and expressing feelings to community members, which then provoked the same strategy across contexts. Meanwhile, stigma triggered the deliberate grief avoidance network by initially suppressing the expression of feelings to community members.Conclusion: Enacted stigma contributes to bereavement coping. Stigma stirs up complex feelings but forces AIDS-orphaned children to suppress expressions, and it increases needs to process grief through meaning making but cuts supporting forces by promoting avoidance. Interventions are imperative to reduce stigma, improve emotion regulation, and facilitate meaning making for people bereaved by stigmatized deaths.Keywords: enacted stigma, bereavement coping, AIDS, orphans, network analysis, parental loss

Jinpeng Xu,1 Guomei Tian,2 Jingran He,1 Fangmin Deng,1 Fangting Chen,1 Qi Shi,1 Jian Liu,1 Hongyu Zhang,1 Ting Zhang,1 Qunhong Wu,1 Zheng Kang1 1School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Zheng Kang, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China, Email kangzheng@hrbmu.edu.cnPurpose: To understand the public’s self-willingness to report medical insurance fraud and their expectations on others, to provide a reference for the government to do a good job in medical insurance anti-fraud.Methods: Data were obtained from a questionnaire survey of 846 respondents in China. Descriptive statistical analyses and multinomial logistic regression were used to analyze the different subjective attitudes of the public toward different subjects when faced with medical insurance fraud and the influencing factors.Results: 511 (60.40%) respondents were willing to report medical insurance fraud, while 739 (87.35%) respondents expected others to report it. 485 (57.33%) respondents were willing and expected others to report medical insurance fraud, followed by those who were not willing but expected others to report it (254, 30.02%). Compared to those who were unwilling to report themselves and did not want others to report, those who believe their reporting is useless (OR=3.13, 95% CI=1.15– 8.33) and those who fear for their safety after reporting (OR=2.96, 95% CI=1.66– 5.26) were more likely to expect others to report. Self-reporting willingness was stronger among the public who were satisfied with the government’s protective measures for the safety of whistleblowers (OR=4.43, 95% CI=1.38– 14.17). The public who believe that both themselves and others have responsibilities to report medical insurance fraud were willing to report and expect others to do the same.Conclusion: The public had a “self-avoidance” and “other-reliance” mentality in medical insurance anti-fraud. The free-rider mentality, lack of empathy, concerns about own risk after reporting, and the interference of decentralized responsibility were important factors contributing to this public mentality. At this stage, the government should prevent the public’s “collective indifference” in medical insurance anti-fraud efforts. Improving the safety and protection of whistleblowers and making everyone feel more responsible and valued may be effective incentives to enhance the public’s willingness to report.Keywords: medical insurance, anti-fraud, whistleblower, subjective attitudes

Ying Wang,1,2,&ast; Yiyi Liu,1– 3,&ast; Xun Zhang,1– 3 Qing Wu1– 3 1Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Anhui Mental Health Center, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wu, Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, 316 Huangshan Road, Hefei, 230022, People’s Republic of China, Tel +8613856919530, Email wuqinghf@163.comPurpose: Sex-based differences in patients with bipolar disorders (BD) are well recognized, and it is well known that the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) are both higher in men than in women. Although metabolic disorders such as NAFLD are common in patients with BD, sex differences and risk factors for NAFLD comorbidity in these patients have not been thoroughly explored. This study aimed to investigate sex differences in patients with comorbid NAFLD and BD and associated risk factors.Methods: This retrospective cross-sectional study included 710 patients with BD. Clinical data of patients with BD, including information on fasting glucose, liver function-related enzymes, relevant lipid data, uric acid, the triglyceride-glucose index (TyG), and demographics, were derived from the hospital electronic medical record system from June 2020 to July 2022. We performed logistic regression analysis and calculated the odds ratios with 95% confidence intervals of factors using t-tests, χ²-tests, and receiver operating characteristic. NAFLD was diagnosed using liver ultrasonography.Results: The prevalence of NAFLD was higher in male patients with BD than in female patients (50.9% vs 38.5%), and there were significant differences in the years of education and marital status (all P< 0.05). Regression analysis showed that the risk factors for comorbidities were the body mass index (BMI), fasting glucose, and apolipoprotein B levels in male patients and the BMI, bipolar disease course, glutamine transpeptidase levels, and the TyG in female patients.Conclusion: Sex-based differences exist in risk factors and in the prevalence of comorbid NAFLD among patients with BD. BMI is a sex-independent risk factor, and clinical attention should be targeted to risk factors associated with comorbid NAFLD related to sex, especially in female patients with BD who presenting a high TyG index.Keywords: sex differences, triglyceride-glucose index, metabolic disorders, prevalence

Yingxian Luo, Qiong Wu, Runtang Meng, Fuzhi Lian, Chen Jiang, Meiyu Hu, Yaxin Wang, Haiyan Ma School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mahaiyan@hznu.edu.cnObjective: To evaluate the associations between serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), with a focus on gender differences, and variations among women pre-and post-menopausal stages.Design: A retrospective cohort study.Setting: A large community-based survey was conducted every two years from 2010 to 2018 in Hangzhou, Zhejiang Province, Southeastern China.Participants: 10,218 participants (40 years or above) without CKD at baseline who underwent three physical examinations were enrolled. CKD was defined as an eGFR of less than 60 mL/min/1.73m2.Methods: Participants with SUA levels were divided into four groups (Q1-Q4) based on baseline SUA quartiles. The Q1 was the reference. By stratifying participants by gender, the relationships between SUA levels and eGFR were investigated using the generalized additive mixture model. The associations of SUA and the risk of incident CKD were examined using multivariate logistic regression models in the generalized estimating equation.Results: After adjusting for confounding variables, a nonlinear association between SUA and eGFR was observed in females, while an approximately linear relationship was observed in males, suggesting that elevated SUA levels are associated with renal function decline. Furthermore, the highest quartile of SUA was associated with a 2.16-fold (95% CI: 1.31– 3.58) increased risk of CKD in males and a 2.76-fold (95% CI: 1.59– 4.78) increased risk in females, compared with the lowest quartile. And the spline curves demonstrated a U-shaped pattern, suggesting a potential threshold effect of SUA on the risk of CKD. Additionally, Subgroup analyses revealed significant associations between elevated SUA levels with CKD in postmenopausal women, but not in premenopausal women.Conclusion: Elevated SUA levels are associated with an increased risk of CKD development and renal function decline in middle-aged and elderly individuals, particularly in postmenopausal women.Keywords: uric acid, estimated glomerular filtration rate, chronic kidney disease, Chinese cohort

Xianyu Xie,1,&ast; Zijun Zhao,2,&ast; Qinde Wu3,&ast; 1Department of Medical Administration, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2School of Public Administration & Law, Fujian Agriculture and Forestry University, Fuzhou, Fujian, People’s Republic of China; 3Department of Education Administration, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinde Wu, Department of Education Administration, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +0086-13365917369, Fax +0086-0591-83325046, Email qdwu88@126.comPurpose: This study aimed to analyze first-choice medical institutions for middle-aged and older adults in Fujian Province to promote the development of hierarchical diagnosis and treatment for them.Patients and Methods: Single factor analysis, disordered multi-classification logistic regression, and multiple correspondence classification were used to analyze the influencing factors of first-choice medical institutions for middle-aged and older adults. A total of 486 valid questionnaires were obtained. The questionnaire was based on Health Service Integration Theory and the behavioral model of Andersen.Results: Age, education level, living area, monthly income, nearest medical institution to home, and integrated health service system understanding significantly influenced respondents’ preference of first medical institution. Middle-aged and older adults were more inclined to visit county and municipal hospitals first. The treatment center’s proximity was also an important determinant of their first-choice selection of medical care.Conclusion: To realize high-quality hierarchical diagnosis and treatment and integrated health service system construction, it is important to improve the service capacity of primary medical institutions, increase the training of family doctors, implement the contract coverage of family doctors, optimize the allocation and geographical layout of primary medical institutions, ensure adequate income levels, and promote township hospital staff.Keywords: hierarchical diagnosis, middle-aged adult, older adult, first medical institution, influencing factors

Lietao Wang,1,&ast; Xin Fu,1,&ast; Min He,1,&ast; Lvyuan Shi,1 Dingyuan Wan,1 Yucong Wang,1 Qin Wu,1 Jing Yang,1 Bayuan Cai,2 Hongtao Xia,3 Hongxu Chen,4 Ge Zhang,5 Xianying Lei,6 Wei Zhang,7 Zhongxue Feng,7 Bo Wang,1 Zhongwei Zhang1 On behalf of Heat Stroke Research Group in Southwestern China1Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Critical Care Medicine, The People’s Hospital of Jiajiang, Leshan, People’s Republic of China; 3Department of Critical Care Medicine, Suining Central Hospital, Suining, People’s Republic of China; 4Department of Critical Care Medicine, The Hospital of Traditional Chinese Medicine of Leshan, Leshan, People’s Republic of China; 5Department of Critical Care Medicine, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 6Department of Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 7Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Wang; Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85422739, Email wchicu@126.com; 716461751@qq.comObjective: The aim of this nationwide multicenter study was to ascertain the risk factors associated with in-hospital mortality in patients with heat stroke admitted to intensive care units (ICUs) and to develop a nomogram for prognostic prediction.Methods: A retrospective analysis was conducted on clinical data collected from ICU patients diagnosed with heat stroke across multiple centers nationwide. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for in-hospital mortality. Based on the results of the multivariate analysis, a nomogram was constructed to estimate the individualized probability of mortality. Internal validation of the nomogram was performed, and its performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).Results: A total of 292 ICU patients with heat stroke were included in this study. Three risk factors, namely Cr (creatinine), AST (aspartate aminotransferase), and SBP (systolic blood pressure), were found to be significantly associated with in-hospital mortality. These risk factors were incorporated into the nomogram, which exhibited good discriminative ability (area under the ROC curve of the training and validation cohorts were 0.763 and 0.739, respectively) and calibration. Internal validation and decision curve analysis confirmed the stability and reliability of the nomogram.Conclusion: This nationwide multicenter study identified key risk factors for in-hospital mortality in ICU patients with heat stroke. The developed nomogram provides an individualized prediction of mortality risk and can serve as a valuable tool for clinicians in the assessment and management of ICU patients with heat stroke.Keywords: heat stroke, intensive care unit, in-hospital mortality, risk factors, nomogram

Fei Meng, Qin Wu, Wei Zhang, Shirong Hou Department of Ultrasound, Xuan Cheng City Central Hospital, Xuancheng, Anhui, People’s Republic of ChinaCorrespondence: Fei Meng, Xuan Cheng City Central Hospital, No. 171, Tonggong Road, Xuanzhou Distinct, Xuancheng, Anhui, 242000, People’s Republic of China, Tel + 86-18956308225, Email Fly_MengUltrasound@163.comBackground: Diabetic kidney disease (DKD) patients have a high risk of suffering from cardiovascular disease (CVD), placing a heavy cost on the public health system. In this study, we intended to develop and validate a shear-wave elastography (SWE)-based radiomics nomogram for predicting the development of CVD in DKD patients. This approach allows extensive use of the valuable information contained in ultrasound images, thus helping clinicians to identify CVD in DKD patients.Methods: Totally 337 and 145 patients constituted the training and validation cohorts, respectively. The radiomics features of the segmented kidney in ultrasound images were extracted and selected to generate the rad-score of each patient. These rad-score, as well as the predictors of risk of CVD occurrence from the clinical characteristics, were included in the multivariate analysis to develop a nomogram. It was further assessed in the training and validation cohorts.Results: Patients with CVD accounted for 30.9% (104/337) in the training cohort and 31.0% (45/145) in the validation cohort. The rad-score was calculated for each patient using 6 features extracted from the ultrasound images. The radiomics nomogram was built with the rad-score, age, systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C). It was superior to the clinical nomogram developed without the rad-score and demonstrated promising discrimination, calibration, and clinical utility in both training and validation cohorts.Conclusion: We developed and validated an SWE-based radiomics nomogram to predict CVD risk in patients with DKD. The model was demonstrated to have a promising prediction performance, showing its potential to identify CVD in DKD patients and assist decision-making for appropriate early intervention.Keywords: radiomics, nomogram, shear-wave elastography, cardiovascular disease, diabetic kidney disease

Qian Wu,1 Jing Shi,2 Juan Huang,3 Delu Gan,1 Lijun Zhang,1 Pu Li1 1Department of Laboratory Medicine, The Second Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Information Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pu Li, Department of Clinical Laboratory, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China, Fax +86-23-63693195, Email lipu@hospital.cqmu.edu.cnBackground: Escherichia coli (E. coli) is a common pathogen in bloodstream infections (BSI), and the production of extended-spectrum beta-lactamases (ESBLs) is its main mechanism of resistance. However, the impact of different ESBL genotypes of E. coli on the resistance to Cefepime (FEP) remains unclear.Methods: A total of 2356 cases of BSI patients were collected. The experimental group included 188 ESBL-positive E. coli strains that were resistant to FEP but sensitive to ceftazidime (CAZ). Antibiotic usage and resistance rates were evaluated through antimicrobial susceptibility testing and antibiotic usage records. The ESBL genotypes were identified, and the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of FEP were determined.Results: In ESBL-positive E. coli, three ESBL genotypes were identified: 188 strains of CTX-M, 130 strains of TEM-1, and 26 strains of OXA-10. Among them, 124 strains carried both CTX-M-9 and TEM-1 genotypes, 22 strains carried two CTX-M genotypes (CTX-M-1 and CTX-M-2), 20 strains carried both CTX-M-9 and OXA-10, and 6 strains carried three genotypes (CTX-M-9, CTX-TEM-1, and OXA-10). The MIC50, MIC90, MPC50, and MPC90 of the 188 ESBL-positive E. coli were 64, 256, 128, and 528, respectively. The MIC values ranged from 32 to 256, while the MPC values ranged from 64 to 528. The MIC50, MIC90, MPC50, and MPC90 of the 40 ESBL-negative E. coli were 0.5, 1, 64, and 128, respectively; the MIC values ranged from 0.25 to 4, while the MPC values ranged from 32 to 256, respectively.Conclusion: ESBL-positive E. coli induces an increase in the MIC value of FEP, leading to an increase in FEP resistance. The inoculation effect also causes a significant increase in the MPC value of FEP, especially the increase in selection index value, indicating selective enrichment and amplification of drug-resistant mutants, resulting in clinical treatment failure.Keywords: Escherichia coli, cefepime, ESBLs, mutant prevention concentration

Junlong Ma,1,2,&ast; Jie Huang,1,&ast; Chan Zou,1 Qian Wu,1 Jinlian Xie,1 Xingfei Zhang,1 Xiaoyan Yang,1 Shuang Yang,1 Ziteng Wu,3 Yan Jiang,3 Sen Yu,3 Xuqing Zhang,4 Guoping Yang,1,5 Mingyuan Li1 1The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 3Nanjing Delova Biotech Co., Ltd., Nanjing, Jiangsu, 210042, People’s Republic of China; 4King-eagle Med Co., Ltd., Changsha, Hunan, 410013, People’s Republic of China; 5Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingyuan Li, Email lmyuan3@126.comBackground: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects.Methods: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg MobicⓇ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated.Results: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15– 60 mg (Cmax and AUC0-t were 5.82– 17.66 μg/mL and 58.08– 251.17 μg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference.Conclusion: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain.Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).Keywords: meloxicam, phase I trial, pharmacokinetic, safety, novel formulation

Wei Sun,1 Qiao Wu,1 Li Gao,2 Zhong Zheng,3 Hu Xiang,1 Kun Yang,1 Bo Yu,1 Jing Yao1 1Department of Psychiatry, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang City, Sichuan Province, People’s Republic of China; 2Department of Neurology, The Third People’s Hospital of Chengdu, Chengdu Institute of Neurological Diseases, Chengdu City, Sichuan Province, People’s Republic of China; 3Neurobiological Detection Center, West China Hospital Affiliated to Sichuan University, Chengdu City, Sichuan Province, People’s Republic of ChinaCorrespondence: Qiao Wu, Department of Psychiatry, the Third People’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang City, Sichuan Province, People’s Republic of China, Email bridgeqiao@foxmail.comAbstract: Transcranial magnetic stimulation (TMS) has become increasingly popular in clinical practice in recent years, and there have been significant advances in the principles and stimulation modes of TMS. With the development of multi-mode and precise stimulation technology, it is crucial to have a comprehensive understanding of TMS. The neuroregulatory effects of TMS can vary depending on the specific mode of stimulation, highlighting the importance of exploring these effects through multimodal application. Additionally, the use of precise TMS therapy can help enhance our understanding of the neural mechanisms underlying these effects, providing us with a more comprehensive perspective. This article aims to review the mechanism of action, stimulation mode, multimodal application, and precision of TMS.Keywords: transcranial magnetic stimulation, mechanism, stimulation mode, multimodal application, precision

Maoze Gao,1,&ast; Yaohui Fang,1,&ast; Zhangrui Liu,1 Xinpeng Xu,1,2 Hua You,1,2 Qifeng Wu1 1School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Institute of Healthy Jiangsu Development, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinpeng Xu, School of Public Health, Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email xuxinpeng@njmu.edu.cnBackground: Effective healthcare utilization throughout pregnancy is essential in protecting mother and child health, but the maternal healthcare utilization and its associated factors among migrant women are still underexplored.Methods: The data came from the 2018 China Migrants Dynamic Survey. Our analysis included 6337 pregnant migrant women. Prenatal healthcare utilization comprises receiving at least 5 antenatal care (ANC) times and establishing the maternal health record within the first 12 weeks of pregnancy. Postnatal healthcare utilization refers to whether an individual received a postpartum visit and a physical health examination within 28 days and 42 days following delivery. A multivariate binary logit model was employed to investigate the factors related to maternal healthcare utilization.Results: 67.15% of the 6337 participants established health records within the first 12 weeks of pregnancy, and 88.35% received at least five ANC visits. 76.88% and 84.20% of migrant pregnant women received a postpartum visit and a health examination respectively. Age was positively correlated with receiving at least five ANC visits (OR:1.245, 95% CI: 1.038– 1.493), a postpartum visit within 28 days (OR: 1.272, 95% CI: 1.107– 1.460) and a physical examination within 42 days after delivery (OR=1.174, 95% CI: 1.002– 1.376). Education, household income, health insurance and maternal health education were positively associated with prenatal and postnatal healthcare utilization (P< 0.05). Number of Children negatively correlated with ANC times (OR: 0.742, 95% CI: 0.613– 0.898) and receiving health examination after delivery (OR: 0.720, 95% CI: 0.610– 0.849).Conclusion: There is still potential for improvement in the maternal healthcare utilization, particularly in postnatal healthcare. Strengthening the follow-up, focusing on those who are younger, have lower socioeconomic status, and are members of ethnic minorities, and continuing to strengthen maternal health education for them can promote the maternal healthcare utilization before and after delivery.Keywords: maternal healthcare utilization, prenatal and postnatal, migrant pregnant women, China

Qixing Wu,&ast; Yiyuan Luo,&ast; Mingming Han, Juan Li, Fang Kang Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Kang, Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei City, Anhui Province, 230036, People’s Republic of China, Tel +86 18155127799, Email kangfang199771@163.comPurpose: This study aimed to investigate the value of the Pain Sensitivity Questionnaire (PSQ) for the prediction of postoperative pain and the relationship between pain sensitivity and postoperative pain in kidney donors undergoing living-related kidney transplantation.Patients and Methods: A total of 148 kidney donors were selected and the preoperative pain sensitivity questionnaire was administered the day before surgery. Kidney donors were assigned to low PSQ group (PSQ < 6.5, n = 76) or high PSQ group (PSQ ≥ 6.5, n = 72). The primary endpoint was the number of patient-controlled analgesia (PCA). Other outcomes included: the incidence of acute pain, flurbiprofen axetil remediation rate, the incidence of chronic pain, neuropathic pain assessment scale (Douleur Neuropathique 4 Questions, DN4), visual analog scale (VAS) at rest after surgery as well as the correlation between PSQ and QST (Quantitative Sensory Testing).Results: The low PSQ group had a significantly lower number of PCA than high PSQ group (P < 0.0001). The incidence of acute pain was 75% in low PSQ group and 100% in high PSQ group (P < 0.0001). Furthermore, flurbiprofen axetil remediation rate was lower in low PSQ group than that in high PSQ group (P = 0.042). The incidence of chronic pain was significantly lower in low PSQ group than in high PSQ group (6.6% vs 61.1%, P < 0.001). Moreover, DN4 was significantly lower in low PSQ group than that in high PSQ group (P < 0.001). The PSQ-mean was significantly negatively correlated with QST in kidney donors. VAS at rest for the low PSQ group were lower than those of the high PSQ group.Conclusion: The PSQ was found to be associated with the intensity or postoperative pain and might be used to screen patients prior to living-kidney transplantation.Keywords: pain, pain sensitivity, pain sensitivity questionnaire, kidney donor

Zhixin Liu,1,2,&ast; Huanyu Zhang,1 Nan Wang,1,&ast; Yajie Feng,1,&ast; Junping Liu,1 Lin Wu,1 Zhaoyue Liu,1 Xinru Liu,1 Libo Liang,1 Jie Liu,3 Qunhong Wu,1 Chaojie Liu4 1Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of China; 3Intensive Care Unit, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Libo Liang; Jie Liu, Email llbhit@163.com; liujie21814@126.comBackground: This study aimed to test the mediating role of anxiety and insomnia in the association between fear of infection and fatigue.Methods: A cross-sectional questionnaire survey was conducted on the nurses deployed to Heihe. A serial multiple mediation model was established to determine the role of anxiety and insomnia in the association between fear of infection and fatigue.Findings: Over half (53.0%) of the study participants reported experiencing fear of infection despite stringent personal protection measures. The scores of anxiety (11.87± 5.19), insomnia (16.33± 5.95), and fatigue (45.94± 12.93) were moderately correlated, with a Pearson correlation coefficient ranging from 0.501 to 0.579. Anxiety, either alone or in combination with insomnia, mediated the association between fear of infection and fatigue.Conclusion: The findings suggest that anxiety and insomnia play a mediating role in the relationship between fear of infection and fatigue. These results emphasize the importance of implementing targeted mental health interventions and work arrangements to address the well-being of healthcare professionals.Keywords: fear of infection, anxiety, insomnia, fatigue, COVID-19

Yanqing Xing,1 Liting Feng,1 Yangdou Dong,2 Yupeng Li,1 Lulu Zhang,1 Qiannan Wu,1 Rujie Huo,1 Yanting Dong,1 Xinrui Tian,1 Xinli Tian3 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Basic Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Cardiology, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xinrui Tian, Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, People’s Republic of China, Tel +8613834575570, Email tianxr@126.com Xinli Tian, Department of Cardiology, Chinese PLA General Hospital, No. 7 Medical Center No. 5 Nanmencang, Dongsijiao, Dongcheng District, Beijing, People’s Republic of China, Email 18600501329@126.comPurpose: Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma.Methods: Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay.Results: We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls.Conclusion: This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.Keywords: asthma, bioinformatics, ferroptosis, GSEA, GSVA, immune microenvironment