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Zhenkang Liang,* Zehong Chen,* Chaowei Zhang, Cui Chen, Wende Yang, Yuxuan Zhang, Hongbo Wei Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People’s Republic of China, Tel +86-020-85253000, Email weihb@mail.sysu.edu.cnPurpose: Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods: We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results: The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion: MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.Keywords: cavernous nerve injury, erectile dysfunction, microvesicles, oxidative stress, ferroptosis

Gengyu Cen,1,&ast; Jun Wang,1,&ast; Xue Wang,1 Yiting Song,1 Shijian Chen,1 Jing Li,2 Qiuhui Huang,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Neurology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email lzj200415@126.comObjective: To investigate the pathogenesis of cancer-related ischemic stroke (CRIS) and to search for reliable biomarkers of CRIS.Methods: Patients with CRIS, only-cancer and only-ischemic stroke who were hospitalized in the First Affiliated Hospital of Guangxi Medical University from May 2022 to January 2024 were recruited, and laboratory and clinical data of the three groups were collected. Peripheral venous blood was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect markers of coagulation (D-dimer) and endothelial integrity (intercellular adhesion molecule-1 (ICAM-1)).Results: The study included 16 patients with CRIS, as well as 16 patients with only-cancer and 16 patients with only-ischemic stroke. Among patients with CRIS, the most common cancer was lung cancer, and the most common pathological type was adenocarcinoma. It was found that compared with patients with only-cancer and only-ischemic stroke, the hemoglobin and lymphocyte percentage in patients with CRIS were decreased (P< 0.05), while the neutrophil percentage and neutrophil to lymphocyte ratio (NLR) were increased (P< 0.05). Compared with only-ischemic stroke group, the lymphocyte absolute value in patients with CRIS was decreased (P< 0.05), and platelet to lymphocyte ratio (PLR), globulin, prothrombin time (PT), international normalized ratio (INR) and ICAM-1 were increased (P< 0.05). D-dimer level was higher in patients with CRIS than in only-cancer group (P< 0.05).Conclusions: In the present study, the increased NLR, PLR, ICAM-1 and D-dimer were expected to be biomarkers of CRIS, indicating that hypercoagulability mediated by cancer inflammation and endothelial damage may be the pathogenesis of CRIS. The novel findings in the present study will facilitate clinicians to identify the patients at high risk of CRIS. Because of the small sample size, the findings need to be validated by prospective large-sample studies in the future.Keywords: cancer-related ischemic stroke, hypercoagulability, pathogenesis, biomarkers

Mark Brommeyer,1,2 Maxine Whittaker,1 Zhanming Liang1 1James Cook University, Townsville, QLD, Australia; 2Flinders University, Adelaide, SA, AustraliaCorrespondence: Mark Brommeyer, College of Business, Government and Law, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia, Email mark.brommeyer@flinders.edu.auIntroduction: Healthcare is experiencing a global period of profound transformation, and digital health shows the promise of dispensing innovative and contemporary service models. However, changes are required to improve the capabilities of health managers in driving successful digital transformation.Objective: This paper aims to explore the organizational barriers that health service managers have encountered when realizing the benefits of a digitally transforming environment. This is part of a larger research study exploring digital competencies for health service managers, with the findings from focus group discussions providing a baseline from which to address the organizational improvements and changes in system capabilities required to assist in realizing the benefits of digital health transformation.Methods: The study is qualitative in nature. It employs focus group discussions to gain an in-depth understanding of the experiences and views of health service managers and identify the benefits and barriers that managers have experienced in introducing digital health in their workplace.Results: Barriers encountered in realizing digital health benefits in the workplace were evidenced across five major themes: (1) change resistance and usage, (2) trust and uniformity, (3) resourcing and procurement, (4) digital literacy, and (5) siloed systems.Discussion: Findings from this study demonstrate that in driving the realization of digital health transformation benefits, health service managers need organizational and system-wide efforts to support managing in the digital health context. The key identified barriers experienced by health service managers include facing human and technical challenges with system adoption and the governance of data-driven decision-making in the digital context.Conclusion: The importance of digital transformation in healthcare is evident and will increasingly become a necessity for organizational survival and success. This study adds important insights into the organizational barriers that health service managers have encountered when realizing the benefits resulting from digital transformation. Addressing these barriers requires macro-, meso- and micro-level system investments. These benefits are enhanced by enabling factors critical for digital health adoption that have been described in key categories involving health system related: (1) policy and system, (2) organizational structure and processes, and human resource management, and (3) people factors. The importance of ensuring the organizational factors driving the realization of benefits in a digitally transforming environment is also addressed and capitalized upon for health service managers.Keywords: healthcare management, health service manager, digital transformation, digital health benefits, workforce development, digital health barriers

Xuanling Chen,1,&ast; Xuewei Qin,1,&ast; Yutong Zhuang,2 Zhengqian Li,3 Zhenhu Liang,4 Hua Zhang,5 Lan Yao,1 Xiaoli Li,6 Jianghong He,7 Xiangyang Guo3 1Department of Anesthesiology, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Institute of Electrical Engineering, Yanshan University, Qinhuangdao, People’s Republic of China; 5Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 6The State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, People’s Republic of China; 7Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo, Peking University, Third Hospital, 49 huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn Jianghong He, Beijing Tiantan Hospital, 119 South Fourth Ring Road West, Fengtai District, Beijing, 100069, People’s Republic of China, Email hejianghong@sina.cnObjective: To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC).Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40– 60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected.Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS− to VS/ UWS and 2 patients in the non-BIS group died during follow-up.Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes.Keywords: chronic disturbance of consciousness, vegetative state/unresponsive wakefulness syndrome, spinal cord stimulation, general anesthesia, bispectral index, improved coma recovery scale

Zhihan Jiang,1,&ast; Yingying Dai,2,&ast; Jing Chang,2 Pingchao Xiang,3 Zhenyu Liang,4 Yan Yin,5 Yongchun Shen,6 Ruiying Wang,7 Bianba Qiongda,8 Hongling Chu,9 Nan Li,9 Xiaoyan Gai,1,10 Ying Liang,1,10 Yongchang Sun1,10 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, GuangZhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 9Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 10Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 13810964766 ; +86 13910979132, Fax +86 108 226 6989, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation.Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred.Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.Keywords: chronic obstructive pulmonary disease, COPD, pulmonary tuberculosis, tuberculosis-associated COPD, protocol

Hao Wang,1 Yinbo Xiao,1 Yumeng Cai,1 Yang Zhou,1 Longyun Chen,1 Jianbin Guo,2 Xiaohua Shi,1 Zhiyong Liang1 1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Zhiyong Liang; Xiaohua Shi, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, Tel +86 10-69159353 ; +86 10-69159365, Email liangzy@pumch.cn; shixiaohua3762@foxmail.comIntroduction: This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer.Methods: Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival.Results: The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone.Conclusion: The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.Keywords: endometrial cancer, lower uterine segment, prognosis

Guojuan Pu,1,2 Zhen Liang,1,2 Jieran Shi,2 Yuan Tao,1,2 Ping Lu,1,2 Huiling Qing,1,2 Junjie Zhang1,2 1Henan Eye Hospital, Henan Eye Institute, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China; 2People’s Hospital of Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Junjie Zhang, Henan Eye Hospital, Henan Eye Institute, Henan Provincial People’s Hospital, and People’s Hospital of Zhengzhou University, Number 7 Weiwu Road, Zhengzhou, 450003, People’s Republic of China, Email zhangjunjie@zzu.edu.cnBackground: Corneal neovascularization (CNV) is a common eye disease that leads to blindness. New treatment strategies are urgently needed due to the limitations of current treatment methods.Methods: We report the synthesis of peptide Nap-FFEEPCAIWF (Comp.3) via chemical conjugation of Nap-FFEE (Comp.2) to antiangiogenic peptide PCAIWF (Comp.1). Comp.3 self-assembled into a hydrogel (gel of 3) composed of nanofibers, which enhanced the antiangiogenic function of the epitope.Results: We developed a novel peptide with an amphiphilic framework, Comp.3, which could self-assemble into a supramolecular hydrogel with a well-ordered nanofiber structure. The nanofibers exhibited good biocompatibility with corneal epithelial cells, presenting a promising strategy to enhance the efficacy of free peptide–based drugs in the treatment of ocular vascular diseases, such as CNV and other angiogenesis-related diseases.Conclusion: Nap-FFEEPCAIWF nanofibers provide an alternative approach to enhancing the therapeutic efficiency of free peptide–based drugs against ocular vascular diseases. Keywords: antiangiogenic peptide, self-assembled, hydrogel, nanofiber, corneal neovascularization

Fangfang Fan,1,2,&ast; Zhe Liang,1,2,&ast; Zhihao Liu,1 Pengfei Sun,1 Lihua Hu,1 Jia Jia,1,2 Yan Zhang,1,2 Jianping Li1,2 1Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China; 2Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Li, Department of Cardiology & Institute of Cardiovascular Disease, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Email lijianping03455@pkufh.comPurpose: Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients.Patients and Methods: This case–control study included 428 case–control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of > 70% and controls with stenosis of < 30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD.Results: Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 μg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 μg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90– 0.99; P = 0.010). Patients with a serine concentration of ≥ 13.41 μg/mL had a lower CHD risk than those with a serine concentration of < 13.41 μg/mL (odds ratio [OR] 0.57, 95% CI 0.39– 0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (Pinteraction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87– 0.98; P = 0.013) than in females.Conclusion: This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.Keywords: serine, coronary heart disease, case–control, one-carbon metabolism

Runzhi Wang,1 Rong Zhao,2 Zhongguo Liang,1 Kaihua Chen,1 Xiaodong Zhu1,3– 6 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia autonomous Region, 010020, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 5Guangxi Clinical Medicine Research Center of Nasopharyngeal Carcinoma, Nanning, Guangxi, 530021, People’s Republic of China; 6Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-Di Road, Nanning, 530021, People’s Republic of China, Tel +86 15778028340, Email zhuxdonggxmu@126.comPurpose: To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population.Patients and Methods: All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan–Meier method.Results: This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18– 2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12– 3.68, P = 0.019), pre-treatment plasma Epstein–Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01– 2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67– 4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk.Conclusion: PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.Keywords: nomogram, platelet distribution width-to-lymphocyte ratio, inflammatory biomarker, locoregionally advanced nasopharyngeal carcinoma, overall survival

Yan Zhang,1,&ast; Senlu Wang,1,&ast; Xinqi Wang,2 Nianqiang Liu,2 Le Wang,2 Xiaomin Wang,1 Zhichao Liang,1 Junan Wang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To analyze the effectiveness of the “Xinjiang Model” for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.Methods: The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze “Xinjiang model” determinants of effectiveness.Results: The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018– 2021 (APC=− 28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012– 2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (P< 0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.Conclusion: The “Xinjiang model” can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.Keywords: pulmonary tuberculosis, implementation effect, registered incidence, determinants, Xinjiang

Yiliang Zhong,1,2,&ast; Jing Wang,3,4,&ast; Zhou Liang,5 Tingcheng Han,3,4 Hua Lu,3,4 Zhaomeng Hou3,4 1Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Department of Spinal Surgery, People’s Hospital of Ganxian District, Ganzhou, People’s Republic of China; 3Department of Orthopedics and Traumatology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, People’s Republic of China; 4Department of Orthopedics and Traumatology, Yancheng TCM Hospital, Yancheng, People’s Republic of China; 5Department of Minimally Invasive Spinal Surgery, Yulin Orthopedic Hospital of Integrated Traditional Chinese and Western Medicine, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaomeng Hou, Department of Orthopedics and Traumatology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, People’s Republic of China, Email houzhaomeng1992@163.comBackground: The increasing utilization of endoscopic lumbar discectomy (ELD) in spinal surgery has sparked widespread interest and research. This study utilizes bibliometric analysis to identify current research trends and advancements in this innovative surgical technique, with the goal of informing and improving surgical practices.Methods: We retrieved relevant literature on ELD from the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as research samples. Various visualization tools, such as VOSviewer, CiteSpace, Scimago Graphica, Pajek, and online bibliometric platform, were employed to generate scientific knowledge maps for the purpose of visual presentation and data analysis.Results: Over the past two decades, there has been significant progress in the research related to ELD, particularly since 2016. China has emerged as the most productive country, while South Korea and the United States have exerted greater academic influence. Tongji University has contributed the highest number of research output, while academic achievements published by Wooridul Spine Hospital are highly esteemed by scholars. Lee SH and Ruetten S are the most prolific author and the most highly cited author, respectively. World Neurosurg has published the highest number of publications, while Spine has become the most influential journal. Clinical Neurology and Surgery are the primary subject categories. Research in this field primarily revolves around improving ELD techniques, evaluating postoperative efficacy and prognosis prediction, studying complications and risk factors, as well as comparative research with other surgical techniques. Keywords such as risk factors, LDH, PETD, lumbar spinal stenosis, degeneration, recurrent herniation, laminectomy, local anesthesia, and foraminoplasty highlight the current research hotspots and future cutting-edge trends.Conclusion: This study employed bibliometric analysis to elucidate the research hotspots and frontiers in ELD. The findings have significant implications for advancing research and development in this field.Keywords: endoscopic lumbar discectomy, bibliometric, visualization analysis, VOSviewer, CiteSpace

Jing Liu,1,&ast; Zeyi Liang,1,&ast; Maocao Zhongla,2 Hongsheng Wang,3 Xu Sun,4 Juanshan Zheng,1 Xuezhi Ding,1 Feng Yang1 1Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, People’s Republic of China; 2Gannan Animal Disease Prevention and Control Center, Hezuo, People’s Republic of China; 3Xiangyang Vocational and Technical College, Xiangyang, People’s Republic of China; 4College of Life Sciences and Engineering, Lanzhou University of Technology, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of enterococcal isolates (Enterococcus faecalis, Enterococcus faecium and Enterococcus hirae) isolated from clinical bovine mastitis cases in Ningxia, China.Patients and Methods: The enterococci were identified by 16S rRNA amplification and sequencing. Antimicrobial resistance was determined by disc diffusion method. Virulence and antimicrobial resistance genes were detected by PCR assays.Results: Overall, 198 enterococcal isolates were identified from 2897 mastitis samples, including 137 (4.7%) E. faecalis, 50 (1.7%) E. faecium and 11 (0.4%) E. hirae. E. faecalis, E. faecium and E. hirae isolates showed high resistance to tetracycline (92.7%, 68.0%, 90.9%), followed by erythromycin (86.9%, 76.0%, 72.7%). The multidrug-resistant strains of E. faecalis and E. faecium were 29 (21.2%) and 13 (26.0%), respectively. The resistance of E. faecalis, E. faecium and E. hirae isolates to tetracycline is mainly attributed to the presence of tetL (alone or combined with tetM and/or tetK), the erythromycin resistance to ermB (alone or combined with ermC and/or ermA). Moreover, cpd (94.2%), gelE (77.4%), efaAfs (93.4%), and esp (79.6%) were the most common virulence genes in E. faecalis. In E. faecium, except for the gene efaAfs (82.0%), other virulence genes are rarely found. Only two strains of E. hirae carrying asa1 gene were detected.Conclusion: The results of this study can provide a reference for the prevention and treatment of bovine mastitis caused by enterococci.Keywords: bovine mastitis, enterococci, antimicrobial resistance, virulence

Shuhan Chen,1,2 Yanle Xie,1,2 Zenghui Liang,1,2 Yu Lu,3 Jingping Wang,4 Fei Xing,1,2 Yuanyuan Mao,1,2 Xin Wei,1,2 Zhongyu Wang,1,2 Jianjun Yang,1,2 Jingjing Yuan1,2 1Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Henan Province International Joint Laboratory of Pain, Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 3Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 4Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USACorrespondence: Jingjing Yuan; Jianjun Yang, Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1, Eastern Jianshe Road, Zhengzhou, Henan Province, 450000, People’s Republic of China, Tel +86 13513719631 ; +86 13783537619, Email yjingjing_99@163.com; yjyangjj@126.comAbstract: Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.Keywords: sleep deprivation, pain, oxidative stress, antioxidants

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

Xiaoyan Yang,1 Liyin Liao,1 Zizhen Liang,1 Shenglong Yu,2 Zhonghui Guo1 1Department of Laboratory Medicine, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, 511400, People’s Republic of China; 2Institute of Cardiovascular Medicine, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, 511400, People’s Republic of ChinaCorrespondence: Zhonghui Guo, Department of Laboratory Medicine, The Affiliated Panyu Central Hospital of Guangzhou Medical University, No. 8, Fuyu East Road, Qiaonan Street, Panyu District, Guangzhou, 511400, People’s Republic of China, Tel +86 20 3485 8850, Email Guo_zhonghui23@163.comObjective: This research aimed to explore the involvement of interleukins (IL) - IL-6, IL-17, IL-21, and IL-23 - in the evolution and diagnosis of non-alcoholic liver fibrosis and cirrhosis.Methods: The study subjects were selected from the patients who visited the Department of Hepatology of X Hospital in Y City from August 2021 to April 2023. Peripheral blood samples were collected. All participants were divided into liver fibrosis, cirrhosis, hepatitis, and healthy subjects four groups. IL-21, IL-17, IL23, IL-6 were detected by double antibody sandwich.Results: The results showed that there was a significant difference in the levels of IL-17, IL-21, and IL-23 among the 4 groups (P< 0.0001). ROC curve analysis showed that the AUC values of IL-17, IL-21 and liver fiber 4 items were > 0.70, suggesting that the diagnostic efficacy of IL-17, IL-21 was similar to that of liver fiber 4 items. Spearman correlation analysis showed that IL-17 had a positive correlation with collagen type III N-peptide, type IV collagen, and Laminin (P < 0.05), and no correlation with Hyaluronic acid (P > 0.05).Conclusion: IL-17, IL-21, and IL-23 play a pivotal role in the inflammatory pathways associated with liver injuries, establishing themselves as potent auxiliary diagnostic markers in identifying liver fibrosis and cirrhosis.Keywords: non-alcoholic liver fibrosis, cirrhosis, diagnostic markers, cytokines

Jingjing Yuan,1,2,&ast; Zenghui Liang,1,&ast; Muhoza Bertrand Geoffrey,1 Yanle Xie,1,2 Shuhan Chen,1,2 Jing Liu,1,2 Yuzhong Xia,1 Huixin Li,1 Yanling Zhao,1 Yuanyuan Mao,1,2 Na Xing,1,2 Jianjun Yang,1,2 Zhongyu Wang,1 Fei Xing1,2 1Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Henan Province International Joint Laboratory of Pain, Cognition and Emotion, Zhengzhou, Henan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Xing; Zhongyu Wang, Department of Anesthesiology, Pain and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road Erqi District, Zhengzhou City, Henan Province, People’s Republic of China, Tel +86-15936275656, Email fccxingf@zzu.edu.cn; wzy781217@163.comPurpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients.Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65– 78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS< 4), frail patients (CFS≥ 4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient’s dose was dependent on the previous patient’s response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded.Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250– 0.284) and 0.301 mg/kg (95% CI 0.284– 0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244– 0.281) and 0.302 mg/kg (95% CI 0.283– 0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia.Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.Keywords: ciprofol, median effective dose, elderly patients, frailty, loss of consciousness

Zetan Chen,1,2 Gang Wu,2 Xiangying Lin,2 Xiaopeng Huang,2 Shuai Zhang,2 Kaihua Chen,1 Zhongguo Liang,1 Xiaodong Zhu1,3,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 3Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-13978873616, Email zhuxdonggxmu@126.comPurpose: Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC).Patients and Methods: From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors.Results: Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis–free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis.Conclusion: High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.Keywords: serum sialic acid, nasopharyngeal carcinoma, prognosis, propensity score matching

Daoda Qi,1,&ast; Yang Chen,1,&ast; Chengyi Peng,1 Yuan Wang,2 Zihao Liang,2 Jingjing Guo,1 Yan Gu1 1Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gu; Jingjing Guo, Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +86 25 83626297, Email guyan703@foxmail.com; guojingjing0017@126.comBackground and Objective: Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era.Methods: A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves.Results: A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3– 5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count < 400/μL, the Activities of Daily Living (ADL) score ≤ 40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤ 7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively.Conclusion: We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.Keywords: early progression, CGA, nomogram, COVID-19, omicron era

Dong Huang,1,&ast; Dingxiu He,2,&ast; Linjing Gong,1,&ast; Wei Jiang,2,&ast; Rong Yao,3 Zongan Liang1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The People’s Hospital of Deyang, Deyang, Sichuan, People’s Republic of China; 3Department of Emergency Medicine, Emergency Medical Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongan Liang, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, People’s Republic of China, Email liangza@scu.edu.cnBackground: There is no predictive tool developed for pneumonia-associated acute respiratory distress syndrome (ARDS) specifically so far, and the clinical risk classification of these patients is not well defined. Our study aims to construct an early prediction model for hospital mortality in patients with pneumonia-associated ARDS.Methods: In this single-center retrospective study, consecutive patients with pneumonia-associated ARDS admitted into intensive care units (ICUs) in West China Hospital of Sichuan University in China between January 2012 and December 2018 were enrolled. The least absolute shrinkage and selection operator (LASSO) regression and then multivariate logistic regression analysis were used to identify independent predictors which were used to develop a nomogram. We evaluated the performance of differentiation, calibration, and clinical utility of the nomogram.Results: The included patients were divided into the training cohort (442 patients) and the testing cohort (190 patients) with comparable baseline characteristics. The independent predictors for hospital mortality included age (OR: 1.04; 95% CI: 1.02, 1.05), chronic cardiovascular diseases (OR: 2.62; 95% CI: 1.54, 4.45), chronic respiratory diseases (OR: 1.87; 95% CI: 1.02, 3.43), lymphocytes (OR: 0.56; 95% CI: 0.39, 0.81), albumin (OR: 0.94; 95% CI: 0.90, 1.00), creatinine (OR: 1.00; 95% CI: 1.00, 1.01), D-dimer (OR: 1.06; 95% CI: 1.03, 1.09) and procalcitonin (OR: 1.14; 95% CI: 1.07, 1.22). A web-based dynamic nomogram (https://h1234.shinyapps.io/dynnomapp/) was constructed based on these factors. The concordance index (C index) of the nomogram was 0.798 (95% CI: 0.756, 0.840) in the training cohort and 0.808 (95% CI: 0.747, 0.870) in testing cohort. The precision–recall (PR) curves, calibration curves, decision curve analyses (DCA) and clinical impact curves showed that the nomogram has good predictive value and clinical utility.Conclusion: We developed and evaluated a convenient nomogram consisting of 8 clinical characteristics for predicting mortality in patients with pneumonia-associated ARDS.Keywords: pneumonia, acute respiratory distress syndrome, mortality, risk factors, nomogram

Jiewei Cui,1,&ast; Yang Li,2,&ast; Qingyan Du,3,&ast; Yuanhui Wei,1 Jinxia Liu,1 Zhixin Liang1 1College of Pulmonary & Critical Care Medicine, 8th Medical Center of Chinese PLA General Hospital, Beijing, 100091, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 3Jiamei Dental Hospital, Beijing, 100143, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixin Liang, Email liangzhixin301@163.comObjective: Bloodstream infection (BSI) is characterized by high mortality, especially among these increasing super-elderly patients (≥ 85 years), and this study was conducted to understand the species distribution, typical clinical features and risk factors for poor prognosis of super-elderly patients with BSI.Methods: Based on previous work, this retrospective study was performed by reviewing an ongoing prospective medical database in a comprehensive tertiary center in China, and all super-elderly patients with BSI in the past 6 years were enrolled in this study.Results: Out of 5944 adult-patients with BSI, there were totally 431 super-elderly patients (≥ 85 years old) enrolled in this study and age ≥ 90 years accounted for 31.1% (134/431). Among these 431 super-elderly patients with BSI, 40 patients (9.3%) were diagnosed with BSI and the remained 401 super-elderly patients (90.7%) were defined as hospital-acquired BSI. The typical feature of these super-elderly patients with BSI was the high proportion of patients with various comorbidities, such as cardiovascular disease (83.8%), ischemic cerebrovascular disease (63.3%) and pulmonary infection (61.0%). The other typical feature was that most (60.1%) of these patients had been hospitalized for long time (≥ 28 days) prior to the onset of BSI, and most patients had received various invasive treatments, such as indwelling central venous catheter (53.1%) and indwelling urinary catheter (47.1%). Unfortunately, due to these adverse features above, both the 7-day short-term mortality (13.2%, 57/431) and the 30-day long-term mortality (24.8%, 107/431) were high. The multivariate analysis showed that both chronic liver failure (OR 7.9, 95% CI 2.3– 27.8, P=0.001) and indwelling urinary catheter (OR 2.3, 95% CI 1.1– 4.7, P=0.023) were independent risk factors for 7-day short-term mortality, but not for 30-day long-term mortality. In addition, the microbiology results showed that the most common species were associated with nosocomial infection or self-opportunistic infection, such as Staphylococcus hominis (18.3%), Staphylococcus epidermidis (11.8%), Escherichia coli (9.7%), Klebsiella pneumoniae (9.3%) and Candida albicans (8.6%, fungi).Conclusion: Super-elderly patients with BSI had typical features, regardless of the pathogenic species distribution and their drug resistance, or clinical features and their risk factors for poor prognosis. These typical features deserved attention and could be used for the prevention and treatment of BSI among super-elderly patients.Keywords: bloodstream infection, elderly, species, risk factor, mortality, aging, central venous catheter, clinical feature

Zhaojun Liang,1,2 Nan Wang,1,2 Chunxue Fan,1,2 Lili Shang,1,2 Yaping Zhang,1,2 Chong Gao,3 Jing Luo1,2 1Division of Rheumatology, Department of Medicine, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory for Immunomicroecology, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Jing Luo, Email ljty966@hotmail.comIntroduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19.Methods: The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma.Results: Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19+B cells, CD4+T cells, CD8+T cells, NK cells, CD4+CD8+T cells and CD4–CD8–T cells (all p< 0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p< 0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p< 0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells.Conclusion: Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.Keywords: coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, adaptive immunity, short-chain fatty acids

Zitian Liang,1,&ast; Ding Chen,2,&ast; Ye Jiang,1 Zhikang Su,2 Yixing Pi,2 Tao Luo,2 Qianzhou Jiang,1 Li Yang,1 Lvhua Guo2 1Department of Endodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China; 2Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Lvhua Guo, Affiliated Stomatology Hospital of Guangzhou Medical University, No. 195 West Dongfeng Road, Guangzhou, 510182, People’s Republic of China, Tel +86-020-81299942, Email 2019686001@gzhmu.edu.cn; 2010686002@gzhmu.edu.cnIntroduction: Effective infection control without irritating the pulp tissue is the key to successful vital pulp therapy. Developing a novel antibacterial biomaterial that promotes dentin regeneration for pulp capping is thus a promising strategy for enhancing vital pulp therapy.Methods: Lithium-doped mesoporous nanoparticles (Li-MNPs) were synthesized using an alkali-catalyzed sol-gel method. The particle size, elemental distribution, surface morphology, pore structure, and ion release from Li-MNPs were measured. Human dental pulp stem cells (hDPSCs) and Streptococcus mutans (S. mutans) were used to evaluate the biological effects of Li-MNPs. In addition, a dental pulp exposure mouse model was used to evaluate the regenerative effects of Li-MNPs.Results: Li-MNPs had a larger surface area (221.18 m2/g), a larger pore volume (0.25 cm3/g), and a smaller particle size (520.92 ± 35.21 nm) than MNPs. The in vitro investigation demonstrated that Li-MNPs greatly enhanced the biomineralization and odontogenic differentiation of hDPSCs through the Wnt/β-catenin signaling pathway. Li-MNPs showed a strong antibacterial effect on S. mutans. As expected, Li-MNPs significantly promoted dentin regeneration in situ and in vivo.Conclusion: Li-MNPs promoted dentin regeneration and inhibited S. mutans growth, implying a possible application as a pulp capping agent in vital pulp therapy.Graphical Abstract: Keywords: lithium, mesoporous nanoparticles, dental pulp stem cells, dentin regeneration, Wnt/β-catenin signaling pathway, antibacterial properties

Jinrong Ning,1,&ast; Guodong Zheng,1,&ast; Yi Cai,1,&ast; Yunguang Hu,2,&ast; Yiqi Liu,1 Enping Lai,1 Baizhong Chen,3 Yujie Liu,1 Ziqi Liang,1 Jijun Fu,1 Minyan Wei1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 2Medical Department, Guangdong Yifang Pharmaceutical Co., Ltd, Foshan, Guangdong, 528200, People’s Republic of China; 3Guangdong Xinbaotang Biological Technology Co., Ltd, Jiangmen, Guangdong, 529000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minyan Wei; Jijun Fu, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China, Tel +86-20-37103268, Email weiminyan@163.com; fujj@gzhmu.edu.cnPurpose: APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy.Methods: The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo.Results: NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation.Conclusion: These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.Graphical Abstract: Keywords: nobiletin, self-assembly micelles, solid dispersion technology, hot melt extrusion, acetaminophen-induced liver injury

Bisheng Shen,1 Baoxin Chen,2 Kuangyi Li,1 Weiyin Cheng,3 Mohammad Mofatteh,4 Robert W Regenhardt,5 Jack Wellington,6 Zhangrong Liang,1 Qi Tang,1 Jingli Chen,1 Yimin Chen7 1Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China; 2Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China; 3Department of Clinical Nutrition, Foshan Hospital of Traditional Chinese Medicine, Foshan City, People’s Republic of China; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 6School of Medicine, Cardiff University, Cardiff, Wales, UK; 7Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of ChinaCorrespondence: Baoxin Chen, Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China, Email P2009495@ipm.edu.mo Kuangyi Li, Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China, Email 13809211066@163.comPurpose: This study aimed to highlight the impact of the COVID-19 pandemic lockdown on emergency department (ED) visits of non-COVID-19 patients in a tertiary hospital and evaluate protocol development during this period.Patients and Methods: Clinical data of patients who visited the ED of Foshan Hospital of Traditional Chinese Medicine during the first-level response in Foshan, Guangdong province in 2020 (from January 23 to February 24) and the same period in 2019 and 2021 were collected. A retrospective cross-sectional analysis was performed to understand the characteristics of critically ill patients and compare the proportion of hospitalizations, deaths, and emergency ambulance calls (EACs).Results: The number of patients presenting to the ED was significantly decreased, with a 37.75% reduction in 2020 (6196) compared to the same period in 2019 (9954). A rise in patient ED presentations was observed in the same period in 2021 (10,503). This decline was mostly in the 15– 45 age group. In 2019, 2020, and 2021, critically ill patients treated by the ED totaled 568 (5.706%), 339 (5.495%), and 590 (5.617%), respectively. Compared to the same period in 2019 and 2021, the proportion of critically ill patients with respiratory system involvement, severe trauma, and poisoning decreased most significantly in 2020 (P< 0.05). In contrast, the rates of EACs, hospitalizations, and deaths increased significantly (P< 0.05).Conclusion: The number of ED visits to hospitals was decreased during the 2020 lockdown, while the rates of EACs, hospitalizations, and deaths increased significantly though there were no documented COVID-19 cases. Optimizing emergency medical resources and ensuring the safety of healthcare providers and patients were essential to provide efficient emergency diagnosis and treatment during the lockdown.Keywords: COVID-19 pandemic, emergency medicine, coping strategies, emergency visit, non-COVID-19 patients

Yunli Zhang,1,2,&ast; Yayuan Liu,1,3,&ast; Bin Qin,1,4 Shiting Tang,1,5 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Intensive Care Unit, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 3Department of Neurology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Neurology, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China; 5Department of Neurology, Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnPurpose: The present study aimed to identify the characteristics, predictors, and imaging features of poor recovery in cases of cerebral venous sinus thrombosis (CVST).Patients and Methods: A total of 290 consecutive adult patients with CVST were enrolled from January 2017 to December 2021 from five hospitals in Nanning, Guangxi. According to the modified Rankin scale (mRS) score at hospital discharge, the patients were classified into good prognosis (GP, mRS ≤ 2) groups and poor prognosis (PP, mRS> 2) groups. Logistic regression was used to identify factors associated with clinical outcomes.Results: Of the 290 patients, 35 were assigned to the PP group and 255 to the GP group. No significant difference in sex was observed between the two groups. Headache (76.21%) was the most frequent symptom of CVST, and local head and neck infection was the major comorbidity (26.21%). Approximately half of the patients (48.62%) had brain injury lesions < 1 cm, and the most commonly affected sinus was the lateral sinus (81.03%). Less-common headaches (odds ratio [OR]: 2.769, p=0.046), altered mental status (OR: 0.122, p< 0.001), hematologic disorder (OR: 0.191, p=0.045), and injury to multiple lobes (OR: 0.166, p=0.041) were associated with poor clinical outcomes.Conclusion: Headache was the most common and protective manifestation of CVST, and disturbances in consciousness were an important indication of poor clinical prognosis. Patients with hematologic diseases also tended to have poor outcomes. No significant correlation was found between the number and location of venous sinus thromboses and clinical prognosis; however, intracranial injury involving multiple lobes was often associated with poor prognosis.Keywords: cerebral venous sinus thrombosis, cerebral infarction, intracranial hemorrhage, hematologic disorder, prognosis

Rong Zhao,1 Zhongguo Liang,1 Kaihua Chen,1 Xiaodong Zhu1– 3 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education/Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Email zhuxdonggxmu@126.comPurpose: There is still uncertainty regarding the prognosis of nasopharyngeal carcinoma (NPC) based on hemoglobin, albumin, lymphocytes, and platelets (HALP) score. The aim of this study was to build and verify a nomogram using HALP score to investigate the prognostic value of NPC and identify low-risk patients in T3-4N0-1 NPC to guide treatment options.Patients and methods: A total of 568 NPC patients with stage T3-4N0-1M0 were recruited in the study, who were given either concurrent chemoradiotherapy (CCRT) or induction chemotherapy (IC) plus CCRT. The prognostic factors of overall survival (OS) were picked by Cox proportional hazards regression analysis to generate a nomogram, which appraised by discrimination, calibration and clinical utility. Patients were stratified according to risk scores calculated by the nomogram, and compared to the 8th TNM staging system using the Kaplan–Meier methods.Results: Multivariate analysis showed that TNM stage, Epstein–Barr virus DNA (EBV DNA), HALP score, lactate dehydrogenase-to-albumin ratio (LAR) and systemic inflammatory response index (SIRI) were independent prognostic indicators for OS, and these factors contained in the nomogram. The nomogram demonstrated a significant enhancement over the 8th TNM staging system in terms of assessing OS (C-index, 0.744 vs 0.615 in the training cohort, P < 0.001; 0.757 vs 0.646 in the validation cohort, P = 0.002). Calibration curves displayed good agreement and the stratification in high-risk and low-risk groups resulted in a significant divergence of Kaplan–Meier curves for OS (P < 0.001). In addition, the decision analysis (DCA) curves confirmed satisfactory discriminability and clinical utility.Conclusion: The HALP score was an independent prognostic factor for NPC. The prognostic function of the nomogram for T3-4N0-1 NPC patients was more accurate compared to the 8th TNM system, facilitating personalized treatment planning.Keywords: Epstein–Barr virus, induction chemotherapy, concurrent chemoradiotherapy, locoregional extension patterns, immunoinflammatory marker

Zeyi Liang,&ast; Jiahao Shen,&ast; Jing Liu, Xu Sun, Yayuan Yang, Yanan Lv, Juanshan Zheng, Xiaoqing Mou, Hongsheng Li, Xuezhi Ding, Feng Yang Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, Gansu, 730050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of Serratia marcescens isolates from clinical bovine mastitis in Ningxia Hui Autonomous Region of China.Methods: S. marcescens was identified by the polymerase-chain reaction of 16S rRNA gene and sequencing. Antimicrobial susceptibility was tested by the disk diffusion method. Genes of resistance and virulence were determined by the PCR.Results: Overall, S. marcescens were confirmed from 32 of 2897 (1.1%) mastitis milk samples. These isolates showed high resistance to cefazolin (30/32, 93.8%) and chloramphenicol (28/32, 87.5%). A 12.5% (4/32) of the isolates displayed multidrug resistance (MDR). The most prevalent resistant genes found in S. marcescens were TEM (32/32, 100%) and CTX-M (24/32, 75.0%; CTX-M-15, 14/32, 43.8%; CTX-M-14, 8/32, 25.0%; CTX-M-65, 2/32, 6.3%) for extended-spectrum beta-lactamase, cmlA (28/32, 87.5%) and floR (16/32, 50.0%) for chloramphenicol resistance, SIM-1 (2/32, 6.3%) for carbapenemases, and sdeB (28/32, 87.5%), sdeY (26/32, 81.3%), sdeR (26/32, 81.3%) and sdeD (20/32, 62.5%) for efflux pumps. Moreover, all isolates carried virulence genes flhD, entB, and kpn, and most of them contained mrkD (30/32, 93.8%), ycfM (26/32, 81.3%), bsmB (26/32, 81.3%), pigP (26/32, 81.3%), kfu (24/32, 75.0%) and shlB (24/32, 75.0%).Conclusion: To our knowledge, this is the first report of genetic determinants for antimicrobial resistance and virulence in S. marcescens isolated from bovine mastitis cases in China. These findings are useful for developing strategies for prevention and treatment of bovine mastitis caused by S. marcescens in China.Keywords: Serratia marcescens, bovine mastitis, antimicrobial resistance, virulence

Defect engineering and doping of semiconductors by ion irradiation are essential in large-scale integration of electronic devices. Here, intense ion pulses from a laser-accelerator, with flux levels up to 1022 ions cm-2 s-1, are used to induce and optimize silicon color centers and photon emitters in the telecom band.

Zhilin Liang,1,&ast; Weiming Liao,2,&ast; Qifu Chen,3 Hui Li,1 Meiling Ye,1 Jin Zou,4 Guofang Deng,1 Peize Zhang1 1Department of Pulmonary Medicine & Tuberculosis, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Thoracic Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, People’s Republic of China; 3Department of Neurosurgery, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Clinical Laboratory, The Third People’s Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, Southern University of Science and Technology, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peize Zhang; Guofang Deng, Tel +8613509650204 ; +8613530027001, Email 82880246@qq.com; jxxk1035@yeah.netAbstract: Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.Keywords: pre-extensive drug resistant TB, tuberculous meningitis, pharmacokinetics, long-tunneled external ventricular drain, drug concentration

Sirou Han,1,2 Min Xu,1 Jiahui Lao,3 Zhanming Liang4 1Hospital Administration Department, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China; 2School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, People’s Republic of China; 3Center for Big Data Research in Health and Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 4College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD, AustraliaCorrespondence: Min Xu, Hospital Administration Department, The Second Affiliated Hospital of Shandong First Medical University, No. 366 Taishan Street, Taian, Shandong Province, 271000, People’s Republic of China, Tel +86-137-9112-0603, Email 13791120603@139.com Zhanming Liang, College of Public Health, Medical and Veterinary Sciences, James Cook University, JCU Townsville Campus, Douglas, Building 41, Room 217, Townsville, QLD, 4870, Australia, Tel +61-7-4781-5040, Email zhanming.liang@jcu.edu.auPurpose: Patient feedback plays a significant role in hospital service improvement. However, how to encourage patient feedback that can guide hospital service improvement is still being explored. By examining patient feedback data related to a tertiary hospital in China that was collected from the “ 12345” Government Service Convenience Hotline (GSCH), the paper discusses the learnings from GSCH in encouraging patient feedback and how quality improvement initiatives have effected the number and types of complaints made by patients and their families via GSCH.Methods: The study retrospectively collected and analyzed complaints on a Tertiary General University-affiliated hospital made via GSCH between 2016 and 2020. Patient care process-related complaints were coded using the health care complaint analysis tool (HCAT) and other complaint data were categorized based on the nature of the complaints. The autoregressive integrated moving average (ARIMA) models and mosaic plots were used to observe complaints trends and different complaint variables, respectively. The relationship between various quality improvement initiatives introduced since 2018 and patient complaints was also tested.Results: Close to 67% (n=2688) of calls made to the GSCH hotlines about the hospital were classified as a complaint including 60.6% vs 39.4% related to patient care process and nonpatient care process, respectively. For patient care process-related complaints, specifically against departments and personnel, 57.72% (n=961) were on clinical departments and 55.87% (n=471) were on doctors. Comparing the proportion of the complaint data in different categories in the two-year period of 2017– 2018 and 2019– 2020, an increase in management problems (47.73% vs 58.50%, P< 0.001) and decrease in relationship problems (33.65% vs 25.69%, P=0.002) were recorded.Conclusion: A unified, transparent, and impartial GSCH platform greatly encourages feedback from patients and families. Feedbacks provide evidence to guide health care organizations in improving the overall experience of patients and the quality of services that they provide.Keywords: patient feedback, medical service, hospital management, hotline, quality improvement, hospital services

Zhongjie Liang,1,2 Huilin Yue,1 Congcong Xu,1 Qian Wang,3 Shengwei Jin2,3 1Department of Neonatology, The Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 3Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Wang; Shengwei Jin, Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of China, Tel +86 577-88002806, Fax +86 577-88832693, Email wqian84@163.com; jinshengwei69@163.comBackground: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants with limited treatments and poor prognosis. Damaged endothelial glycocalyx leads to vascular permeability, lung edema and inflammation. However, whether hyperoxia increases neonatal pulmonary microvascular permeability by degrading the endothelial glycocalyx remains unknown.Methods: Newborn mice were maintained in 60– 70% O2 for 7 days. Protectin DX (PDX), an endogenous lipid mediator, was injected intraperitoneally on postnatal d 0, 2, 4 and 6. Lung samples and bronchoalveolar lavage fluid were taken at the end of the study. Primary human umbilical vein endothelial cells (HUVECs) were cultured in 80%O2.Results: Hyperoxia exposure for 7 days led to neonatal mice alveolar simplification with less radial alveolar count (RAC), mean linear intercept (MLI) and mean alveolar diameter (MAD) compared to the control group. Hyperoxia exposure increased lung vascular permeability with more fluid and proteins and inflammatory factors, including TNF-α and IL-1β, in bronchoalveolar lavage fluid while reducing the heparan sulfate (HS), the most abundant component of the endothelial glycocalyx, in the pulmonary endothelial cells. PDX relieve these changes. PDX attenuated hyperoxia-induced high expression of heparanase (HPA), the endoglycosidase that shed endothelial glycocalyx, p‐P65, P65, and low expression of SIRT1. BOC‐2 and EX527 abolished the affection of PDX both in vivo and intro.Conclusion: In summary, our findings indicate that PDX treatment relieves hyperoxia‐induced alveolar simplification, vascular leakage and lung inflammation by attenuating pulmonary endothelial glycocalyx injury via the SIRT1/NF‐κB/ HPA pathway.Keywords: bronchopulmonary dysplasia, endothelial glycocalyx, inflammation, protectin DX

Shiting Tang,1,&ast; Liuyu Liu,1,&ast; Zhouhua Xie,2 Yaoqin He,2 Yunli Zhang,3 Yiju Xie,4 Shijian Chen,1 Yayuan Liu,1 Yunfei Wei,1,5 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 3Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Neurology, Wuming Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Email liangzhijian@gxmu.edu.cn Yunfei Wei, Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email danggege@163.comObjective: Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS).Methods: Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS.Results: A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%.Conclusion: This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.Keywords: tubercular meningitis, Ischemic stroke, tubercular meningitis-related Ischemic stroke, independent risk factor

Chao Zhang,1,2,&ast; Bingshao Liang,1,&ast; Zhile Xiong,1,2 Zhuwei Liang,1,2 Hao Cai,1 Huamin Zhong,1 Yongqiang Xie,1 Yuanwei Xie,2 Xiaochun Liu,2 Shiying Xie,2 Fangjun Lan,2 Zhenwen Zhou2 1Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Clinical Laboratory, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenwen Zhou, Clinical Laboratory, Longgang District Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86 13925097897, Email zzw6248@126.comPurpose: Chlorhexidine and mupirocin are often prescribed to children in affected communities to prevent colonization and transmission of Staphylococcus aureus, but this has led to an increasing rate of biocide resistance. In this study, we aimed to determine the distribution of biocide resistance genes among S. aureus isolates from school-age children in Guangzhou, investigate chlorhexidine gluconate and mupirocin susceptibility and clonal complex (CC) genotypes in strains carrying biocide-resistance genes, and further explore the role of biofilms in this resistance.Patients and Methods: Antibiotic resistance and multilocus sequence genotyping were performed on 722 S. aureus isolates from previous study. The distribution of nine biocide genes (qacA/B, mupA, mepA, sepA, norA, lmrS, smr, mupB, qacG) was determined by PCR. Isolates carrying qacA/B or mupA genes were further tested for susceptibility to chlorhexidine gluconate (CHG) and mupirocin and biofilm formation abilities.Results: The most prevalent of the nine biocide resistance genes were mepA (95.57%), followed by norA (78.81%), lmrS (77.01%), and sepA (58.17%). The qacG gene was not detected. Distribution of sepA was significantly decreased in CC30 and CC45 genotypes, and presence of sepA was associated with resistance to antibiotics such as CLI, ERY, TCY, SXT, CIP, and LVX. In addition, 64 (94.1%, n=68) qacA/B+ isolates showed CHG resistance, 12 (100.0%, n=12) mupA+ isolates were mupirocin resistant, and 4 (80%, n=5) and 5 (100%, n=5) qacA/B+mupA+ isolates were CHG and mupirocin resistant, respectively. Of these 85 isolates, 98.8% (n=84) had different degrees of biofilm-forming abilities, which were positively associated with CHG and mupirocin resistance.Conclusion: The distribution of biocide resistance genes was associated with special CCs. The qacA/B and mupA genes are highly associated with resistance to CHG and mupirocin, and biofilm formation was found to contribute to this biocide resistance.Keywords: Staphylococcus aureus, biocide resistance genes, qacA/B, children, chlorhexidine, mupirocin, biofilm formation

Guoyan Tang,1,&ast; Fengyan Wang,1,&ast; Zhenyu Liang,1,&ast; Cuixia Liang,2,&ast; Jinling Wang,3,&ast; Yuqiong Yang,1 Wanyi Tang,1,4 Weijuan Shi,1 Guoqiang Tang,3 Kai Yang,5 Zihui Wang,1 Qiasheng Li,1 Hualin Li,1 Jiaxuan Xu,1 Deyan Chen,2 Rongchang Chen5 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Neusoft Medical Systems Co., Ltd, Shenyang, People’s Republic of China; 3Qingyuan Chronic Disease Prevention Hospital, Qingyuan Occupational Disease Prevention Hospital, Qingyuan, People’s Republic of China; 4Qingyuan People’s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China, Email chenrc@vip.163.com Zhenyu Liang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email 490458234@qq.comBackground: Pulmonary vascular alteration is an important feature of chronic obstructive pulmonary disease (COPD), which is characterized by distal pulmonary vascular pruning in angiography. We aimed to further investigate the clinical relevance of pulmonary vasculature in COPD patients using non-contrast computed tomography (CT).Methods: Seventy-one control subjects and 216 COPD patients completed the questionnaires, spirometry, and computed tomography (CT) scans within 1 month and were included in the study. Small pulmonary vessels represented by percentage of cross-sectional area of pulmonary vessels smaller than 5 mm2 or 5– 10 mm2 to the total lung fields (%CSA< 5 or %CSA5– 10, respectively) were measured using ImageJ software. Spearman correlation was used to investigate the relationship between %CSA< 5 and airflow limitation. A receiver operating characteristic (ROC) curve was built to evaluate the value of %CSA< 5 in discriminating COPD patients from healthy control subjects. Segmented regression was used to analyze the relationship between %CSA< 5 and %LAA-950 (percentage of low-attenuation areas less than − 950 HU).Results: We found a significant correlation between %CSA< 5 and forced expiratory volume in one second (FEV1) percentage of predicted value (%pred) (r = 0.564, P < 0.001). The area under the ROC curve for the value of %CSA< 5 in distinguishing COPD was 0.816, with a cut-off value of 0.537 (Youden index J, 0.501; sensitivity, 78.24%; specificity, 71.83%). Since the relationship between %CSA< 5 and %LAA-950 was not constant, performance of segmented regression was better than ordinary linear regression (adjusted R2, 0.474 vs 0.332, P < 0.001 and P < 0.001, respectively). As %CSA< 5 decreased, %LAA-950 slightly increased until an inflection point (%CSA< 5 = 0.524) was reached, after which the %LAA-950 increased apparently with a decrease in %CSA< 5.Conclusion: %CSA< 5 was significantly correlated with both airflow limitation and emphysema, and we identified an inflection point for the relationship between %CSA< 5 and %LAA-950.Keywords: computed tomography, pulmonary vascular pruning, airflow limitation, emphysema, chronic obstructive pulmonary disease

1D organic metal halide hybrids (OMHHs) exhibit strongly anisotropic optical properties, highly efficient light emission, and large Stokes shift, holding promise for novel photodetection and lighting applications. However, the fundamental mechanisms governing their unique optical properties and in particular the impacts of surface effects are not understood. Herein, 1D C4N2H14PbBr4 by polarization‐dependent time‐averaged and time‐resolved photoluminescence (TRPL) spectroscopy, as a function of photoexcitation energy, is investigated. Surprisingly, it is found that the emission under photoexcitation polarized parallel to the 1D metal halide chains can be either stronger or weaker than that under perpendicular polarization, depending on the excitation energy. The excitation‐energy‐dependent anisotropic emission is attributed to fast surface recombination, supported by first‐principles calculations of optical absorption in this material. The fast surface recombination is directly confirmed by TRPL measurements, when the excitation is polarized parallel to the chains. The comprehensive studies provide a more complete picture for a deeper understanding of the optical anisotropy in 1D OMHHs.

Ling Lu,1,&ast; Qiaoyan Liang,2,&ast; Xinyi Zhang,3 Yumeng Xu,3 Dehua Meng,4 Zhaofeng Liang3 1Child Healthcare Department, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Health Care Department, People’s Liberation Army Navy No. 971 Hospital, Qingdao, People’s Republic of China; 3School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China; 4Department of Allergy, Dongtai People’s Hospital, Yancheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaofeng Liang, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, People’s Republic of China, Email liangzhaofeng@ujs.edu.cn Dehua Meng, Department of Allergy, Dongtai People’s Hospital, 02 Fukang West Road, Yancheng, Jiangsu, 224200, People’s Republic of China, Email 2798184241@qq.comAbstract: Gastric cancer (GC) is one of the most common malignant cancers that seriously affect human health. Autophagy is a highly conserved self-defense mechanism found to plays an important role in the occurrence, progression, drug resistance, and prognosis of GC. Noncoding RNAs (ncRNAs) play a critical role in the occurrence and development of a variety of diseases including GC. In recent years, increasing attention has been given to research on autophagy-related ncRNAs, such as miRNA, lncRNA, and circRNA in GC. Herein, we briefly summarize the roles, functions, and the research progress of autophagy and autophagy-related ncRNAs in GC with a focus on the potential application in GC tumorigenesis, development, prognosis, and drug resistance. We also discussed prospects of clinical application, future research direction, and challenges in future research of autophagy-related ncRNAs.Keywords: gastric cancer, autophagy, noncoding RNA, function

Yunfei Wei,1,2,&ast; Shiting Tang,1,&ast; Zhouhua Xie,3 Yaoqin He,3 Yunli Zhang,4 Yiju Xie,5 Shijian Chen,1 Liuyu Liu,1 Yayuan Liu,1 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Tuberculosis, The Fourth People’s Hospital of Nanning City, Nanning, People’s Republic of China; 4Department of Neurology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Department of Neurology, Wuming hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnObjective: There have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).Methods: Active pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.Results: A total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.Conclusion: The findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.Keywords: pulmonary tuberculosis, ischemic stroke, tuberculosis-related ischemic stroke, independent risk factor, pathogenesis

Yi Lu,1 Jiaxi Yu,1 Qiuping Dong,2 Yan Du,3 Zheng Liang1 1Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Cancer Cell Biology, Tianjin’s Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 3Department of Operating Theatre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Zheng Liang, Department of Otorhinolaryngology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, Tel +8618802230827, Email liangzheng01@tmu.edu.cnmailtoPurpose: The involvement of dedicator for cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor for Rac1, in immune infiltration in stomach adenocarcinoma (STAD) remains unclear.Methods: The UALCAN database was used to analyze the expression of the DOCK family. The Kaplan–Meier method and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to assess the prognostic value of the DOCK family in STAD. Furthermore, the correlation between expression of DOCK4 as well as other immune-related marker genes and tumor immune infiltration in STAD was explored using the TIMER and GEPIA websites. Subsequently, the relationship between DOCK4 expression and clinical characteristics was verified using the UALCAN database. Finally, DOCK4 mutation was analyzed via the TIMER2.0 and cBioPortal databases and the DOCK4 protein-protein interaction networks were constructed using the GeneMANIA and STRING websites.Results: DOCK4 was found to be a new prognostic biomarker in STAD. DOCK4 expression in tumors was thoroughly evaluated relative to paracancerous tissues; overexpression of DOCK4 had a negative impact on the prognosis of patients with STAD. DOCK4 was found to be significantly associated with tumor immune infiltration in STAD.Conclusion: In summary, DOCK4 is a potential regulator of the recruitment and regulation of immune-infiltrating cells, thus serving as a valuable prognostic biomarker in STAD.Keywords: DOCK4, stomach adenocarcinoma, immune infiltration, prognostic biomarker, TME

Zhengyan Liang,1 Jinqing Wang,1 Minqiang Zhang,1– 4 Yingshi He,1 Jiaxin Quan,1 Da Yi1 1School of Psychology, South China Normal University, Guangzhou, People’s Republic of China; 2Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou, People’s Republic of China; 3Center for Studies of Psychological Application, School of Psychology, Guangzhou, People’s Republic of China; 4Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of ChinaCorrespondence: Minqiang Zhang, School of Psychology, South China Normal University, No. 55, West of Zhongshan Avenue, Tianhe District, Guangzhou, 510631, People’s Republic of China, Email zhangminqiang@m.scnu.edu.cnIntroduction: There are two types of master’s qualifications in China. One is the academic qualification that pays more attention to academic research, aiming to cultivate research-oriented talents; while the other is the application-oriented qualification that focuses more on practical ability, aiming to cultivate applied-oriented talents. The purpose of this study is to explore the impact of the COVID-19 on the learning activities of postgraduate students, as well as the differences in the extent to which the learning activities of postgraduate students of different qualification types are affected and their mental health status.Methods: A self-constructed scale for the pandemic’s impact on master’s students, the self-rating anxiety scale and the self-rating depression scale were applied in the study. The single- and multi-group latent class analyses were used to investigate the impact of the pandemic on postgraduate students of different qualification types.Results: A total of 2818 responses were collected. The single-group latent class analysis identified four classes. The multi-group latent class analysis showed that no absolute homogeneity existed between different groups. In general, the number of academic master’s students affected was greater than application-oriented master’s students. Application-oriented master’s students were more affected by course activities, while academic master’s students were more affected by academic and social activities. Results show that individuals more affected had higher levels of anxiety and depression. Compared to course activities, impacts on social activities were more likely to cause anxiety and depression.Discussion: Universities can provide a more flexible way of assistance to different qualification types of postgraduate students. Furthermore, social activities play an important role in the mental health of postgraduate students. Therefore, under the background of normalization of pandemic prevention and control, schools should pay more attention to students’ interpersonal communication activities to help relieve students’ anxiety, depression, and other negative emotions.Keywords: COVID-19 pandemic, application-oriented postgraduate students, academic postgraduate students, learning activities, multi-group latent class analysis

Peipei Han,1– 3,&ast; Lin Hou,3,4,&ast; Zhenwen Liang,2 Wuxiong Chen,5 Junxue Li,5 Yazhou Cheng,5 Wenjing Zhou,2 Siya Zeng,2 Jiangtao Pan,2 Lanshan Xu,2 Yi Wang,2 Yangyi Chen,2 Qi Guo1– 3 1Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 3Department of Rehabilitation Medicine, TEDA International Cardiovascular Hospital, Cardiovascular Clinical College of Tianjin Medical University, Tianjin, People’s Republic of China; 4Child Mental Health and Rehabilitation Center, Shenzhen Maternity & Child Health Care Hospital, Shenzhen, People’s Republic of China; 5Department of Rehabilitation Medicine, Shanghai Health Rehabilitation Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Guo, College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, 201318, People’s Republic of China, Tel/Fax +86-22-8333-6977, Email guoqijp@gmail.comBackground: Few longitudinal studies have explored exploring the relationship between sleep duration and sarcopenia. Evidence concerning the relationship between sleep duration and sarcopenia is limited and inconsistent. The purpose of this 3-year prospective study was to explore whether sleep duration was associated with sarcopenia onset in suburb-dwelling older Chinese individuals.Methods: This was a prospective study that included 754 Chinese suburb-dwelling men and women aged ≥ 60 years (men n=327, mean age 65.24± 4.87 years) who were not initially diagnosed with sarcopenia. We defined sarcopenia using the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia. Self-reported sleep duration was a component of the interview measured by trained interviewers. Subjects were categorized into 3 groups at baseline [short: < 6 h, medium: 6– 8 h, and long: > 8 h].Results: The incidence of sarcopenia during the 3-year follow-up was 12.2%. Multivariate logistic regression analyses showed that after adjustments for potential confounders long sleep duration was independently associated with sarcopenia incidence from baseline through the 3-year follow-up: when using the 6– 8 h sleep duration group as a reference, the adjusted ORs for sarcopenia of the groups who slept < 6 and > 8 hours were 2.74 (95% CI 1.05– 7.13) and 1.84 (95% CI 1.07– 3.14).Conclusion: Both short and long sleep durations were associated with a greater incidence of sarcopenia. Thus, sleep duration should be considered when developing prevention and management strategies for sarcopenia.Keywords: longitudinal study, older, sarcopenia, sleep duration, suburb-dwelling

Rong Zhao,1 Zhongguo Liang,1 Kaihua Chen,1 Xiaodong Zhu1– 3 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education/Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China, Tel +86 13978873616, Email zhuxdonggxmu@126.comPurpose: To establish and validate a nomogram to predict overall survival in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) based on inflammatory biomarkers and nutritional indicators.Patients and Methods: A total of 1304 patients who underwent concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) or adjuvant chemotherapy (AC) were included in the study. The prognosis factors of overall survival (OS) were selected by Cox regression analysis to establish the nomogram. Concordance index (C-index), calibration curves, decision curve analysis (DCA) and Kaplan–Meier curves were used to evaluate the nomogram.Results: Using multivariate Cox analysis of clinically important variables, the following variables were incorporated in the prediction of OS: age, gender, T stage, N stage, pre-treatment plasma Epstein–Barr virus (EBV) DNA, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), lactic dehydrogenase-to-albumin ratio (LAR) and prognostic nutritional index (PNI). The discriminative ability, clinical usefulness and calibration of the nomogram revealed good predictive ability as indicated by the C-index (0.717 in nomogram and 0.602 in the 8th AJCC staging system), decision curves, calibration curves and K-M curves.Conclusion: Inflammatory biomarkers and nutritional indicators of survival for LA-NPC were selected to create a nomogram predicting OS. The proposed nomogram resulted in more accurate prognostic prediction than 8th AJCC staging system.Keywords: locoregionally advanced nasopharyngeal carcinoma, inflammatory biomarker, nutritional indicator, nomogram, overall survival

Yayuan Liu,1,&ast; Lizhi Lu,1,&ast; Xuemin Cheng,1 Qixiong Qin,1 Yunfei Wei,2 Dacheng Wang,3 Haihua Li,4 Guohui Li,5 Hongbin Liang,6 Shengyu Li,7 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Province, People’s Republic of China; 3Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, 536000, Guangxi Province, People’s Republic of China; 4Department of Neurology, Fusui County People’s Hospital, Chongzuo, 532100, Guangxi Province, People’s Republic of China; 5Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, 543002, Guangxi Province, People’s Republic of China; 6Department of Neurology, Cenxi People’s Hospital, Cenxi, 543200, Guangxi Province, People’s Republic of China; 7Department of Neurology, The Affiliated Wuming Hospital of Guangxi Medical University, Nanning, 530100, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530000, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnPurpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke.Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden’s J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors.Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051– 1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002– 1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628– 3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index.Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.Keywords: independent risk factors, carcinoembryonic antigen, D-dimer, neutrophil count

Dongdong Xue,1 Jingzhao Han,1 Ze Liang,1 Lin Jia,1 Yifan Liu,1,2 Hongfang Tuo,1 Yanhui Peng1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Department of Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanhui Peng, Department of Hepatobiliary Surgery, Hebei General Hospital, No. 348 Heping West Road, Xinhua District, Shijiazhuang, 050051, Hebei Province, People’s Republic of China, Tel/Fax +86-311-859 8321, Email yhpeng@hebmu.edu.cnAbstract: As a common malignant tumor worldwide, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory, even though treatment methods have improved. Despite the developments in traditional chemotherapy and emerging targeted immunotherapy, the problem of recurrence and metastasis of HCC and adverse effects on survival and prognosis are still serious. Drug resistance is a daunting challenge that impedes HCC treatment. Exosomes, a class of extracellular vesicles ranging in size from 30 to 100 nm, have been the focus of recent studies. Exosomes can activate various signaling pathways and regulate the tumor microenvironment with their cargo, which includes functional lipids, proteins, and nucleic acids. Thus, they change the phenotype of recipient cells via exosome-mediated communication. Exosomes secreted by tumors or stromal cells can also transfer drug-resistant traits to other tumor cells. However, their effects on drug resistance in HCC are not completely understood. In this review, we summarize and discuss the underlying relationship between exosomes and drug resistance in HCC. In addition, we also show that exosomes may act as candidate biomarkers for predicting and monitoring drug responses and as potential targets or vectors to reverse the drug resistance of HCC.Keywords: hepatocellular carcinoma, exosome, tumor microenvironment, targeted therapy

Shiyu Zhang, Zhihai Liang, Xuelian Xiang, Li Liu, Huiying Yang, Guodu Tang Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Province, People’s Republic of ChinaCorrespondence: Guodu Tang, Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, 22 Shuangyong Road, Nanning City, Guangxi Province, People’s Republic of China, Tel +86 13739139408, Email tangguodu@stu.gxmu.edu.cnBackground: The pathogenesis of acute pancreatitis (AP) and the relationship between acute pancreatitis and hypertriglyceridemia are complex and not fully understood. The purpose of this study was to identify the hub genes along with common differentially expressed genes (DEGs) between acute pancreatitis and hypertriglyceridemia.Methods: We downloaded three gene expression profiles of AP and one gene expression profile of hypertriglyceridemia from the Gene Expression Omnibus (GEO) database and filtered the DEGs based on the above four datasets. Next, we identified the hub genes by performing the Gene Ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction (PPI) construction. We also constructed the miRNA-hub gene network and established mouse models with hypertriglyceridemia and AP using a high-fat diet and injection of caerulein (CAE), respectively. Finally, the immunohistochemical analysis was used to verify the differential expressions of hub genes in AP, hypertriglyceridemia, and normal pancreatic tissue.Results: A total of 105 DEGs associated with AP and 149 DEGs associated with hypertriglyceridemia were identified. Additionally, we identified six hub genes of AP, all of which were closely related to the cytoskeleton while two DEGs genes were common in both AP and hypertriglyceridemia. We also verified their expression in mouse models. Finally, a network of miRNA-mRNA was also constructed, and the top seven interactive miRNAs (hsa-mir-1– 3p, hsa-mir-5195– 3p, hsa-mir-145– 5p, hsa-let-7b-5p, hsa-mir-10b-5p, hsa-mir-206, and hsa-mir-613) targeting the most hub genes were identified.Conclusion: Overall, we identified six hub genes associated with AP and two common DEGs associated with AP and hypertriglyceridemia along with seven miRNAs that may regulate AP. This study could provide new ideas for further elucidation of the pathogenesis of hypertriglyceridemia-induced acute pancreatitis in the future.Keywords: acute pancreatitis, biomarkers, hypertriglyceridemia-induced pancreatitis, bioinformatics

Lei Yang,1,&ast; Dingxiu He,2,&ast; Dong Huang,1,&ast; Zhongwei Zhang,3 Zongan Liang1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Emergency Medicine, The People’s Hospital of Deyang, Deyang, Sichuan, People’s Republic of China; 3Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongan Liang Tel +8618980601259Email liangza@scu.edu.cnPurpose: Risk factors and prognostic model of fatal outcomes need to be investigated for the increasing number of immunocompromised hosts (ICHs) who are hospitalized for severe pneumonia with high hospital mortality.Patients and Methods: In this single-center, retrospective study, we recruited 1,933 ICHs with severe pneumonia who were admitted to the intensive care unit (ICU) in West China hospital, Sichuan university, China between January, 2012 and December, 2018. Clinical features, laboratory findings, and fatal outcomes were collected from electronic medical records. Patients were randomly separated into a 70% training set (n=1,353) and a 30% testing set (n=580) for the development and validation of a prediction model. All data within 24 hours of ICU admission were compared between survivors and non-survivors. The risk factors were identified through LASSO and multivariate logistic regression analysis, and then used to develop a predicting nomogram. The nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU was validated by C-index, AUC (area under the curve), calibration curve, and Decision Curve Analysis (DCA).Results: Eight risk factors, including age, fever, dyspnea, chronic renal disease, platelet counts, neutrophil counts, PaO2/FiO2 ratio, and the requirement for vasopressors, were adopted in a nomogram for predicting hospital mortality. The nomogram had great predicting accuracy with a C-index of 0.819 (95% CI=0.795– 0.842) in the training set, and a C-index of 0.819 (95% CI=0.783– 0.855) in the testing set for hospital mortality. Additionally, the nomogram had well-fitted calibration curves. DCA demonstrated that the nomogram was clinically beneficial.Conclusion: This study developed a novel nomogram for predicting hospital mortality of ICHs with severe pneumonia in the ICU. Validation showed good discriminatory ability and calibration, indicating that the nomogram was expected to be a superior predictive tool for doctors to identify risk factors and predict mortality, and might be generally applied in clinical practice after more external validations.Keywords: immunocompromised, severe pneumonia, ICU, risk factors, nomogram

Xi Zhang,1,&ast; Hongyan Wang,1,&ast; Chenzhen Du,1 Xiaoyun Fan,2 Long Cui,3 Heming Chen,4 Fang Deng,5 Qiang Tong,6 Min He,7 Mei Yang,8 Xingrong Tan,9 Lin Li,10 Zerong Liang,11 Yaqin Chen,12 Deqing Chen,13 David G Armstrong,14 Wuquan Deng1 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing University, Chongqing, People’s Republic of China; 2Department of Endocrinology, Hospital for Occupational Diseases of Chongqing, Chongqing, People’s Republic of China; 3Department of Endocrinology, Armed Police Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Endocrinology, Ankang Central Hospital, Ankang, Shaanxi, People’s Republic of China; 5Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, People’s Republic of China; 6Department of Endocrinology, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 7Department of Endocrinology, The People’s Hospital of Shapingba District, Chongqing, People’s Republic of China; 8Department of Endocrinology, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China; 9Department of Endocrinology, The 9th People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 10Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 11Department of Endocrinology, Chongqing Red Cross Hospital, People’s Hospital of Jiangbei District, Chongqing, 400020, People’s Republic of China; 12Department of Endocrinology, The People’s Hospital of Shizhu, Chongqing, People’s Republic of China; 13Department of Endocrinology, The People’s Hospital of Rongchang, Chongqing, People’s Republic of China; 14Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng Email wuquandeng@cqu.edu.cnBackground: Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy’s clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions.Methods: A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy.Results: Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up.Conclusion: Patients’ adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.Keywords: custom-molded offloading footwear, high-risk diabetic foot, patient adherence

Min Zhang,1,2,&ast; Ziwen Wang,1,3,&ast; Zhenshan Liang,4 Niya Hu2 1Department of Blood Transfusion, The Third Affiliated Hospital of Nanchang University, Nanchang City, 330006, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Nanchang, Nanchang City, 330006, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Children’s Hospital of Nanchang University, Nanchang City, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhang; Niya Hu Email zhangmin_20212021@163.com; 364621603@qq.comIntroduction: Janibacter caused bacteriemia is one of the rare infections.Methods: In the present study, we report the first isolation of Janibacter, a rare bacterial infection, from a bacteremia patient in China. Its 16S rDNA was amplified and designated as Janibacter YFY001, which belongs to J. indicus. In addition, its genome was sequenced through combined second- and third-generation genome sequencing methods.Results: Based on its genome, we identified many virulence factors, such as catalase, gelatinase, FbpABC systems, and resistant genes, among others. Interestingly, three genomic islands were found in YFY001 by comparing its genome to environmental Janibacter strains.Discussion: Our study not only provides the necessary genomic information for in-depth study of Janibacter, but also provides a novel methodology for studying future cases of rare bacterial infection.Keywords: bacteriemia, Janibacter, genomic sequencing

Qing Zeng,1 Zhengyan Liang,1 Minqiang Zhang,1– 4 Yuanlin Xia,1 Jia Li,1 Derong Kang,1 Da Yi,1 Jinqing Wang1 1School of Psychology, South China Normal University, Guangzhou, People’s Republic of China; 2Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou, People’s Republic of China; 3Center for Studies of Psychological Application, School of Psychology, Guangzhou, People’s Republic of China; 4Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhengyan Liang; Minqiang ZhangSchool of Psychology, South China Normal University, No. 55, West of Zhongshan Avenue, Tianhe District, Guangzhou, 510631, People’s Republic of ChinaEmail 1064197956@qq.com; 2640726401@qq.comIntroduction: The COVID-19 pandemic broke out and has spread globally since 2019. It became a public health concern. This pandemic has brought tremendous changes in students’ lives and modes of learning. Graduate students are likely to be more affected as they are a part of a special training program. According to the main-effect model, social support has a positive effect on mental health. The pandemic has exerted a negative impact on the social support of individuals, and as a result, the behavior of a person is more likely to be at risk and has resulted in psychological crisis in people/individuals.Methods: A sample of 3137 graduate students responded to the instrument developed to assess the impact of the pandemic on the academic activities and performance, Self-rating Anxiety Scale and Self-rating Depression Scale.Results: The results showed that: 1) the pandemic impacted the academic support and performance of graduate students in varying degrees, 21% of graduate students experienced anxiety, and 33.9% of graduate students experienced depressive symptoms in varying degrees; 2) academic support variables (ie, academic exchange with mentors and peers) and academic performance variables (ie, data collection and thesis writing) were significantly associated with anxiety and depressive symptoms; 3) the model fitted the data well (RMSEA = 0.029; SRMR = 0.014; TLI = 0.99; CFI = 0.996). The direct effects of academic support on anxiety and depressive symptoms were significant. The impact on academic performance played a mediating role between the impact on academic support, anxiety, and depressive symptoms.Discussion: Academic support significantly affected academic performance, which in turn affected anxiety and depressive symptoms. So, it implies that, due to the pandemic, the academic support for graduate students had decreased, resulting in deterioration in academic performance, causing anxiety and depressive symptoms.Keywords: academic support, academic performance, anxiety, depressive symptoms, COVID-19 pandemic, graduate students

Zhen Liang, Zhen Zhang, Jingjing Yang, Ping Lu, Tianyang Zhou, Jingguo Li, Junjie Zhang Henan Eye Hospital, Henan Provincial People’s Hospital & People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Jingguo Li; Junjie ZhangHenan Eye Hospital, Henan Provincial People’s Hospital & People’s Hospital of Zhengzhou University, Number 7 Weiwu Road, Zhengzhou, People’s Republic of ChinaEmail lijingguo@zzu.edu.cn; zhangjunjie@zzu.edu.cnIntroduction: Fungal keratitis (FK) remains a severe sight-threatening disease, and case management is difficult due to ocular intrinsic barriers and drug shortages. Econazole (ECZ), a broad-spectrum antifungal agent, is limited in ocular applications due to the poor water solubility and strong irritant property.Methods: We successfully prepared solid-lipid nanoparticle-based ECZ eye drops (E-SLNs) by microemulsion method, and the physicochemical properties of E-SLNs were investigated. Corneal permeability, antifungal ability against Fusarium spp., irritation and bioavailability compared to ECZ Suspension (E-Susp) were evaluated in vitro and in vivo.Results: E-SLNs were a uniform and stable system which had an average particle size of 19 nm and a spherical morphology. E-SLNs also exhibited controlled release, enhanced antifungal activity without irritation. The pharmacokinetic analysis in vivo confirmed that E-SLNs showed an improved ocular bioavailability and the drug concentration in the cornea were above minimum inhibitory concentration (MIC) for 3 h after single administration.Conclusion: The E-SLNs colloid system is a promising therapeutic approach for fungal keratitis and could serve as a candidate strategy for other ocular diseases.Keywords: fungal keratitis, solid-lipid nanoparticles, econazole, topical administration, corneal penetration

Jiahong Guo,1 Junying Li,2 Hua Wei,1 Zhaozhi Liang1 1Department of Nephrology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, 453000, People’s Republic of China; 2Department of Nephrology, The Affiliated Hospital of Qingdao University Pingdu district, Pingdu City, Qingdao, Shandong, 266000, People’s Republic of ChinaCorrespondence: Junying LiDepartment of Nephrology, The Affiliated Hospital of Qingdao University Pingdu District, No.369 Shanghai Road, Qingdao, Pingdu City, Shandong, 266000, People’s Republic of ChinaEmail lijunying2020@sina.cnBackground: Type 2 diabetes (T2D) is aglobal health burden that accounts for about 90% of all cases of diabetes. Injury to the kidneys is aserious complication of type 2 diabetes. Maackiain, apterocarpan extracted from roots of Sophora flavescens, has been traditionally used for various disease conditions. However, nothing is known about its possible potential effect on HFD/STZ-T2D-induced nephrotoxicity.Methods: In this study, T2D rat model is created by high-fat diet (HFD) for 2 weeks with injection of asingle dose of streptozotocin (35mg/kg body weight). T2D rats were orally administered with maackiain (10 and 20mg/kg body weight) for 7 weeks.Results: Maackiain suppressed T2D-induced alterations in metabolic parameters, lipid profile and kidney functionality markers. By administering 10 and 20mg/kg maackiain to T2D rats, it was able to reduce lipid peroxidation while improving antioxidant levels (SOD, CAT, and GSH). Furthermore, the present study demonstrated the molecular mechanisms through which maackiain attenuated T2D-induced oxidative stress (mRNA: Nrf2, Nqo-1, Ho-1, Gclc and Gpx-1; protein: NRF2, NQO-1, HO-1 and NOX-4), inflammation (mRNA: Tlr, Myd88, IκBα, Mcp-1, Tgf-β, col4, Icam1, Vcam1 and E-selectin; Protein: TLR4, MYD88, NF-κB, IκBα, MCP-1; levels: TNF-α and MCP-1) and apoptosis (mRNA: Bcl-2, Bax, Bad, Apaf-1, Caspase-9 and Caspase-3; protein: Bcl-2, Bax, Caspase-3 and Caspase-9) mediated renal injury. Additionally, significant improvement in kidney architecture was observed after treatment of diabetic rats with 10 or 20mg/kg maackiain.Conclusion: Maackiain protects the kidney by decreasing oxidative stress, inflammation, and apoptosis to preserve normal renal function in type 2 diabetes.Keywords: high-fat diet, streptozotocin, oxidative stress, inflammation, apoptosis, kidney