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Weihua Xu,1 Jiayu Xu,1 Yingying Zhou,1 Weiwei Yang,1 Hui Huang,1 Jun Xue,1 Jing Zhang2 1Ultrasound Medicine Department, Zhabei Central Hospital in Jing’an District, Shanghai, People’s Republic of China; 2Ultrasound Medicine Department, Daning Community Health Service Center in Jing’an District, Shanghai, People’s Republic of ChinaCorrespondence: Weihua Xu, Ultrasound Medicine Department, Zhabei Central Hospital in Jing’an District, Shanghai, People’s Republic of China, Tel +86-13917752615, Email 835233143@qq.comPurpose: To explore the early diagnostic value of superb microvascular imaging (SMI) features within the rotator cuff gap for frozen shoulder.Patients and Methods: This prospective study enrolled patients with acute early-stage frozen shoulder seeking treatment at Zhabei Central Hospital in Jing’an District, Shanghai, between July 2021 and December 2022 were enrolled in this study. Healthy controls were collected in a 1:1 ratio from the same hospital’s physical examination center. All participants underwent SMI and power Doppler ultrasound (PDUS) of the rotator cuff gap.Results: The study included 79 patients with frozen shoulder and 77 healthy controls. Compared with the healthy control group, the patient group had a higher proportion of hypoechoic rotator cuff gap (81.0% vs 48.1%, P< 0.001), a thicker coracohumeral ligament (2.60± 1.01 vs 2.03± 0.97, P< 0.001), a thicker glenohumeral joint capsule (3.10± 0.99 vs 2.46± 1.17, P< 0.001), and elevated blood grading using SMI (P< 0.001) and PDUS (P=0.014). The highest area under the curve (AUC) was observed for SMI blood flow grading (AUC=0.824, 95% CI: 0.755– 0.880, P< 0.001), resulting in 82% sensitivity and 77% specificity when using a cutoff of 1. SMI blood flow grading was associated with external rotation < 30° (P=0.007) and abduction < 30° (P=0.013) but not with internal rotation < 30° (P=0.630) or flexion < 30° (P=0.562).Conclusion: The grading of SMI blood flow may emerge as a valuable predictive indicator for the early stages of frozen shoulder. This simple ultrasound technique holds the potential to enhance the diagnostic process, enabling early initiation of treatment and potentially improving patient outcomes.Keywords: adhesive capsulitis of the shoulder, microcirculation, ultrasonography, early diagnosis, predictive value

Xian Du,1,&ast; Jun Hu,1,&ast; Jianhua Xue,1 Yuan Zhuang,2 Xuefeng Tang,1 Zhiyue Xu1 1Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People’s Republic of China; 2The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyue Xu; Xuefeng Tang, Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), 67 Dajishan, Wuxi, 214065, People’s Republic of China, Email hepenxiaozi@163.com; 978665164@qq.comPurpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients’ quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients.Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ 2 tests and logistic regression models.Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue.Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.Keywords: non-alcoholic fatty liver disease, fatigue, exercise, anxiety, sleep

Yao Wang,1,&ast; Mingtang Zeng,1,&ast; Tianfei Fan,1 Ming Jia,2 Ruxi Yin,1 Jia Xue,1 Longjun Xian,3 Ping Fan,1 Mei Zhan1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Nanchong Institute for Food and Drug Control, Nanchong, People’s Republic of China; 3Department of Thoracic Surgery, Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Fan; Mei Zhan, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email m13980602288@163.com; mandyzhanmei@163.comAbstract: Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.Keywords: MOF, ZIF-8, cell membrane, biomimetic drug delivery

Xia Li,1 Yue Jin,1 Jian Xue2 1Department of Molecular Diagnosis, Northern Jiangsu People’s Hospital, Yangzhou, People’s Republic of China; 2Department of Emergency Medicine, Yizheng People’s Hospital, Yangzhou, People’s Republic of ChinaCorrespondence: Yue Jin, Department of Molecular Diagnosis, Northern Jiangsu People’s Hospital, No. 98, Nantong West Road, Yangzhou, Jiangsu Province, People’s Republic of China, Email yyue_king@163.comAbstract: Collagen, the predominant protein constituent of the mammalian extracellular matrix (ECM), comprises a diverse family of 28 members (I–XXVIII). Beyond its structural significance, collagen is implicated in various diseases or cancers, notably breast cancer, where it influences crucial cellular processes including proliferation, metastasis, apoptosis, and drug resistance, intricately shaping cancer progression and prognosis. In breast cancer, distinct collagens exhibit differential expression profiles, with some showing heightened or diminished levels in cancerous tissues or cells compared to normal counterparts, suggesting specific and pivotal biological functions. In this review, we meticulously analyze the expression of individual collagen members in breast cancer, utilizing Transcripts Per Million (TPM) data sourced from the GEPIA2 database. Through this analysis, we identify collagens that deviate from normal expression patterns in breast cancer, providing a comprehensive overview of their expression dynamics, functional roles, and underlying mechanisms. Our findings shed light on recent advancements in understanding the intricate interplay between these aberrantly expressed collagens and breast cancer. This exploration aims to offer valuable insights for the identification of potential biomarkers and therapeutic targets, thereby advancing the prospects of more effective interventions in breast cancer treatment.Keywords: collagen, breast cancer, extracellular matrix, prognostic marker

Jinli Xue,1 Yige Wu,1 Meng Chen2 1Research Center for Energy Economics, School of Business Administration, Henan Polytechnic University, Jiaozuo, People’s Republic of China; 2Shandong Provincial Territorial Spatial Ecological Restoration Center, Jinan, People’s Republic of ChinaCorrespondence: Meng Chen, Email yuanlinlin8807@163.comPurpose: Idiosyncratic deals (I-deals), a novel human resource management implement, has significantly contributed to attracting, retaining and motivating personnel to enhance creativity. Building upon self-categorization theory, this study investigates the impact of I-deals on creativity and the moderating role of psychological safety in this process by perceived insider status.Participants and Methods: To mitigate common method bias and causal lag effects, this study was conducted in three phases with a half-month interval for data collection. In this study, a total of 331 employees from six enterprises in China were selected to test the hypotheses using Bootstrap and Johnson-Neyman methods.Results: Results show that I-deals have a positive influence on creativity. Perceived insider status acts as intermediary between I-deals and creativity; Psychological safety strengthens the influence of I-deals on perceived insider status and further enhances the indirect influence of I-deals on creativity through perceived insider status.Conclusion: This study demonstrates that organizations can leverage the unique characteristics of I-deals to fully showcase the diverse talents of their personnel, while simultaneously enhancing their psychological security. This, in turn, empowers employees to confidently propose new ideas and methods, thus catalyzing the generation of creativity.Keywords: I-deals, perceived insider status, psychological safety, creativity, self-categorization theory

Bo-Lun Zhang,1 Jia Liu,2 Guanghao Diao,2 Jianping Chang,1 Junshuai Xue,1 Zhen Huang,1 Hong Zhao,1 Lingxiang Yu,2 Jianqiang Cai1 1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, the Fifth Medical Center of the PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianqiang Cai, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel +86-10-87787100, Fax +86-10-67709698, Email caijianqiang@cicams.ac.cnPurpose: We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤ 20 ng/mL).Patients and Methods: Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings.Results: We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651– 0.721). The nomogram model’s clinical application value surpassed that of standard HCC staging systems.Conclusion: The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.Keywords: hepatocellular carcinoma, alpha-fetoprotein-negative, immunity, inflammation, nutrition, recurrence-free survival

Xin Y, Zhang W, Mao C, et al. Onco Targets Ther. 2020;13:1833–1844. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 with images from unrelated articles. Specifically, The images for Figure 4B and 4D have been duplicated with images for Figures 1C, 2E and 6D from Li C, Zhang Y, Tang Y, Xiao J, Gao F, Ouyang Y, Cheng X. LncRNA CRNDE modulates cardiac progenitor cells’ proliferation and migration via the miR-181a/LYRM1 axis in hypoxia. J Thorac Dis. 2020;12(5):2614-2624. https://doi.org/10.21037/jtd.2020.03.22. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jiaojiao Xue,1 Ziwei Zhang,1 Yuting Sun,2 Di Jin,3 Liming Guo,1 Xiangyan Li,4 Daqing Zhao,4 Xiaochun Feng,5 Wenxiu Qi,4 Haoyu Zhu5 1College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Nephrology, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 5Department of Nephropathy and Rheumatology in Children, Children’s Medical Center, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of ChinaCorrespondence: Wenxiu Qi, Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Biomacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel +86-431-860177630, Email qiwenxiu0517@163.com Haoyu Zhu, Department of Nephropathy and Rheumatology in Children, Children’s Medical Center, First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel +86-431-81953813, Email doctorzhuhaoyu163@163.comAbstract: Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between the bloodstream and the walls of blood vessels. These versatile cells serve myriad functions, including the regulation of vascular tension and the management of hemostasis and thrombosis. Inflammation constitutes a cascade of biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently a protective mechanism, dysregulated inflammation can precipitate a host of vascular pathologies. ECs play a critical role in the genesis and progression of vascular inflammation, which has been implicated in the etiology of numerous vascular disorders, such as atherosclerosis, cardiovascular diseases, respiratory diseases, diabetes mellitus, and sepsis. Upon activation, ECs secrete potent inflammatory mediators that elicit both innate and adaptive immune reactions, culminating in inflammation. To date, no comprehensive and nuanced account of the research progress concerning ECs and inflammation in vascular-related maladies exists. Consequently, this review endeavors to synthesize the contributions of ECs to inflammatory processes, delineate the molecular signaling pathways involved in regulation, and categorize and consolidate the various models and treatment strategies for vascular-related diseases. It is our aspiration that this review furnishes cogent experimental evidence supporting the established link between endothelial inflammation and vascular-related pathologies, offers a theoretical foundation for clinical investigations, and imparts valuable insights for the development of therapeutic agents targeting these diseases.Keywords: endothelial cells, endothelial inflammation, vascular-related diseases, atherosclerosis, diabetes mellitus, cardiovascular diseases

Qiongyang Zhou,1,&ast; Yue Ji,2,&ast; Yanzhu Lv,3 Jing Xue,3 Yuhui Wang,3 Yin Huang4 1Department of Acupuncture and Moxibustion, The First People’s Hospital of Wenling, Wenling, People’s Republic of China; 2First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Department of Acupuncture, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yin Huang, Email colbycovington@163.comBackground: Acupuncture may be effective to treat post-stroke cognitive impairment (PSCI). We aimed to evaluate the reliability of the systematic reviews/meta-analyses (SRs/MAs) evidence regarding acupuncture treatment of PSCI.Methods: The methodological quality was appraised with Methodological Quality of Systematic Reviews 2 (AMSTAR-2). We evaluated reporting quality with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and evidence quality with Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system.Results: The inclusion criteria were met by fifteen reviews. All studies assessed by AMSTAR-2 had critically poor methodological quality due to the limitations on the lack of the provision of the list of excluded trails, screening of duplicate study, and protocol registration. For reporting quality, response rate of “yes” was less than 50% in Q5 (protocol and registration topic), Q8 (Search) and Q23 (Additional analysis). Evidence quality of outcome measures was low or worse with GRADE because when the data was qualitatively synthesized, low quality and small sample size trials provided the data.Conclusion: Acupuncture may be beneficial for PSCI. Because of limitations and inconsistent conclusions, further research is needed to provide higher evidence for acupuncture on PSCI.Keywords: acupuncture, treatment, cognitive impairment, stroke, evidence

Jue Wang,1 Shaoting Wen,2 Jiaolong Xue3 1Business School, Open University of Henan, Zhengzhou, People’s Republic of China; 2School of Management, Guangdong Ocean University, Zhanjiang, People’s Republic of China; 3Business School, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jiaolong Xue, Email jiaolongxue@scu.edu.cnPurpose: Although user engagement has been paid increasing attention, the work on user disengagement is scarce, and little is understood about how overloads elicited by excessive social commerce activities affect user disengagement. Based on the stimulus-organism-response (SOR) framework and psychological reactance theory (PRT), the authors aimed to investigate the effects of social commerce overloads (SCOs) on user disengagement, its influential mechanism, and the buffer effect of guanxi.Participants and Methods: The authors conducted an online survey to collect the data and then examined our theoretical model and hypotheses. This study employed SPSS 20.0 software and Amos 24.0 software to examine the hypothesized relationships and the model.Results: Social commerce overloads (ie, information overload (IO), social overload (SO), and communication overload (CO)) positively impact reactance via inferences of manipulative intent (IMI) and compulsive perception (CP); IMI and CP positively influence reactance; IMI, CP, and reactance positively affect user disengagement (ie, neglecting behavior and blocking behavior); guanxi has the buffer effect on the relationship between IMI (CP) and user disengagement, negatively moderates the impacts of IMI on user disengagement (ie, neglecting behavior and blocking behavior), and negatively moderates the effects of CP on blocking behavior but not neglecting behavior.Conclusion: The findings of this study contribute to the literature on PRT and user disengagement by displaying the effects of excessive social commerce activities on user disengagement and uncovering the buffer effect of guanxi, which can help social e-commerce practitioners better reduce the negative effect of social commerce overloads.Keywords: social commerce overloads, inferences of manipulative intent, reactance, guanxi, user disengagement

Junshuai Xue,1 Yang Liu2 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan City, People’s Republic of ChinaCorrespondence: Yang Liu, Department of General surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 18560088317, Email liuyang_sdu@126.comAbstract: Mesenchymal stromal/stem cells (MSCs) have the ability of self-renewal, the potential of multipotent differentiation, and a strong paracrine capacity, which are mainly used in the field of clinical medicine including dentistry and orthopedics. Therefore, tissue engineering research using MSCs as seed cells is a current trending directions. However, the healing effect of direct cell transplantation is unstable, and the paracrine/autocrine effects of MSCs cannot be effectively elicited. Tumorigenicity and heterogeneity are also concerns. The combination of MSCs as seed cells and appropriate vector materials can form a stable cell growth environment, maximize the secretory features of stem cells, and improve the biocompatibility and mechanical properties of vector materials that facilitate the delivery of drugs and various secretory factors. There are numerous studies on tissue engineering and inflammation of various biomaterials, mainly involving bioceramics, alginate, chitosan, hydrogels, cell sheets, nanoparticles, and three-dimensional printing. The combination of bioceramics, hydrogels and cell sheets with stem cells has demonstrated good therapeutic effects in clinical applications. The application of alginate, chitosan, and nanoparticles in animal models has also shown good prospects for clinical applications. Three-dimensional printing technology can circumvent the shortage of biomaterials, greatly improve the properties of vector materials, and facilitate the transplantation of MSCs. The purpose of this narrative review is to briefly discuss the current use of MSC-based carrier biomaterials to provide a useful resource for future tissue engineering and inflammation research using stem cells as seed cells.Keywords: mesenchymal stromal/stem cells, vector biomaterial, tissue engineering, inflammation, cell transplantation

Junxian Ren,1,&ast; Rongcheng Yu,1,&ast; Jingyan Xue,1 Yiqi Tang,1 Sihui Su,1 Chenxi Liao,1 Quanyi Guo,2 Weimin Guo,3 Jinxuan Zheng1 1Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China; 2Institute of Orthopedics, Chinese PLA General Hospital, Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People’s Republic of China; 3Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimin Guo, Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +86 20 87755766&num;6236, Email guowm5@mail.sysu.edu.cn Jinxuan Zheng, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuan West Road, Guangzhou, 510055, People’s Republic of China, Tel +86 20 83802802, Email zhengjx27@mail.sysu.edu.cnAbstract: The maintenance of bone homeostasis includes both bone resorption by osteoclasts and bone formation by osteoblasts. These two processes are in dynamic balance to maintain a constant amount of bone for accomplishing its critical functions in daily life. Multiple cell type communications are involved in these two complex and continuous processes. In recent decades, an increasing number of studies have shown that osteogenic and osteoclastic extracellular vesicles play crucial roles in regulating bone homeostasis through paracrine, autosecretory and endocrine signaling. Elucidating the functional roles of extracellular vesicles in the maintenance of bone homeostasis may contribute to the design of new strategies for bone regeneration. Hence, we review the recent understandings of the classification, production process, extraction methods, structure, contents, functions and applications of extracellular vesicles in bone homeostasis. We highlight the contents of various bone-derived extracellular vesicles and their interactions with different cells in the bone microenvironment during bone homeostasis. We also summarize the recent advances in EV-loaded biomaterial scaffolds for bone regeneration and repair.Keywords: bone, homeostasis, metabolism, extracellular vesicles, regeneration

Dehua Wu1 &ast;, Baojuan Ye1 &ast;, Chunyan Tang,2,3 Jingjing Xue,2,3 Qiang Yang,1 Fei Xia1 1School of Psychology, School of Education, Center of Mental Health Education and Research, Jiangxi Normal University, Nanchang, People’s Republic of China; 2Health Education and Counseling Center, Nanchang Medical College, Nanchang, People’s Republic of China; 3Health Education and Counseling Center, Jiangxi Health Vocational College, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Tang, Nanchang Medical College/Jiangxi Health Vocational College, No. 689 Huiren Avenue, Xiaolan Economic Development Zone, Nanchang, Jiangxi Province, Email tangchunyan@ncmc.edu.cnBackgrounds and Aims: Self-compassion is important for authentic-durable happiness, particularly during the COVID-19 pandemic. To better understand the potential complexity of effects, this study sought to explore (a) the mediating role of meaning of life in the association between self-compassion and authentic-durable happiness and (b) the moderating role of COVID-19 burnout in the relationship between self-compassion and meaning of life.Methods: We conducted a cross-sectional online survey study in China from February 1 to 14, 2021. Online survey questionnaire technique and convenience sampling method were used for data collection. Participants anonymously completed the measures of self-compassion scale short form, COVID-19 burnout scale, meaning in life questionnaire, and subjective authentic-durable happiness scale. The data were examined utilizing Pearson’s r correlations and moderated mediation analysis.Results: This study included 1165 Chinese college students (Mage = 19.68 years, SD = 1.37). Self-compassion (M = 3.39, SD = 0.49) was significantly positively associated with authentic-durable happiness (M = 3.82, SD = 0.66) (r = 0.45, p < 0.001), and mediation analyses indicated that meaning of life (M = 4.65, SD = 0.86) partially mediated this association (indirect effect = 0.103, SE = 0.016, 95% CI = [0.073, 0.135]). Moderated mediation analysis further revealed that COVID-19 burnout (M = 1.87, SD = 0.72) buffered the relation between self-compassion and meaning of life (β = − 0.05, p < 0.033).Discussion and Conclusion: Findings of this study shed light on a correlation between self-compassion and authentic-durable happiness. In addition, this study underlines the importance of intervening in COVID-19 burnout among college students and enhancing the meaning of life in order to promote and safeguard authentic-durable happiness in the setting of COVID-19.Keywords: coronavirus, students, self-compassion, meaning of life, happiness, psychological burnout

Qing-Xia Wang,1 Jiao Xue,1 Mei-Jie Shi,2 Yu-Bao Xie,2 Huan-Ming Xiao,2 Sheng Li,2 Ming Lin,2 Xiao-Ling Chi2 1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Xiao-Ling Chi, Department of Hepatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China, Tel +86+39318398, Fax +86-020-81867705, Email chixiaolingqh@163.comBackground: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel proposed concept that is being recognized worldwide. Both chronic hepatitis B (CHB) and MAFLD have been independently attributed to an increased risk of disease development to cirrhosis. However, it is still unclear whether MAFLD is associated with an increased risk of cirrhosis in CHB patients.Aim: This study aimed to analyze the impact of MAFLD on the risk of cirrhosis in CHB patients.Methods: In this retrospective cohort study, consecutive CHB patients with or without MAFLD were enrolled from January 1st, 2007, to May 1st, 2020, in Guangdong Provincial Hospital of Chinese Medicine. Inverse probability treatment weighting (IPTW) was performed to balance the covariates across groups. The weighted Kaplan–Meier analysis and Cox regression analysis were used to compare both groups for the risk of cirrhosis.Results: A total of 1223 CHB patients were included in this study during the median follow-up of 5.25 years; of these patients, 355 were CHB-MAFLD patients. After IPTW, the weighted Kaplan–Meier analysis showed that the weighted cumulative incidence of cirrhosis was significantly higher in patients with MAFLD than that in patients without MAFLD (12.6% versus 7.1%, P=0.015). In the weighted multivariate Cox analysis, coexisting MAFLD was related to an increased risk of cirrhosis [adjusted weighted hazard ratio (HR) 1.790; P =0.020]. Age (> 40 years, adjusted weighted HR, 1.950; P=0.015), diabetes mellitus (adjusted weighted HR, 1.883; P=0.041), non-antiviral treatment (adjusted weighted HR, 2.037; P=0.013), and baseline serum HBV DNA levels (> 2.4 log10 IU/mL, adjusted weighted HR, 1.756; P=0.045) were significant risk factors for cirrhosis.Conclusion: We found that MAFLD was associated with a higher risk of cirrhosis in CHB patients.Keywords: chronic hepatitis B, metabolic dysfunction-associated fatty liver disease, hepatic steatosis, cirrhosis

Jianjun Jiang,1,&ast; Junshuai Xue,2,&ast; Yang Liu1 1Department of General Surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Tel +86 18560088317, Email E-mail:liuyang_sdu@126.comBackground: Most studies to date have focused on predicting the risk of venous thromboembolism (VTE), but prediction models about mortality risk in VTE are rarely reported. We sought to develop and validate a multivariable model to predict the all-cause mortality risk in patients with acute VTE in emergency settings.Methods: A total of 700 patients were included from Qilu Hospital of Shandong University and were randomly assigned into training set (n=490) and validation set (n=210) in an 7:3 ratio. Multivariate logistics regression analysis was performed to identify independent variables and develop a prediction model, which was validated internally using bootstrap method. The discrimination, calibration and clinical utility were evaluated by receiver operating characteristic curve (ROC) analysis, Hosmer-Lemeshow (HL) test, Kaplan-meier (KM) analysis and decision curve analysis (DCA).Results: There were 52 patients (10.6%) dying and 437 (89.4%) surviving in training set. Age (odds ratio [OR]: 4.158, 95% confidence interval [CI]: 2.426– 7.127), pulmonary embolism (OR: 1.779, 95% CI: 1.124– 2.814), platelet count (OR: 0.507, 95% CI: 0.310– 0.830), D-dimer (OR: 1.826, 95% CI: 1.133– 2.942) and platelet/lymphocyte ratio (OR: 2.166, 95% CI: 1.259– 3.727) were independent risk variables associated with all-cause mortality. The model had good predictive capability with an AUC of 0.746 (95% CI: 0.668,0.825), a sensitivity of 0.769 (95% CI: 0.607,0.889), a specificity of 0.672 (95% CI: 0.634,0.707). The validation model had an AUC of 0.739 (95% CI: 0.685,0.793), a sensitivity of 0.690 (95% CI: 0.580,0.787), a specificity of 0.693 (95% CI: 0.655,0.729). The model is well calibrated and the HL test showed a good fit (χ2=5.291, p=0.726, Nagelkerke R2=0.137). KM analysis and DCA showed a good clinical utility of the nomogram.Conclusion: This study identified independent variables affecting all-cause mortality in patients with acute VTE, and developed a prediction model and provided a nomogram with good prediction capability and clinical utility.Keywords: venous thromboembolism, prediction model, mortality, risk variable, platelet/lymphocyte ratio

Jinli Xue,1 Mengting Zhu,2 Yanan Guo,3 Demin Kong4 1Research Center for Energy Economics, School of Business Administration, Henan Polytechnic University, Jiaozuo, People’s Republic of China; 2School of Management, Shanghai University, Shanghai, People’s Republic of China; 3School of Financial Management, Zhejiang Financial College, Hangzhou, People’s Republic of China; 4School of Humanities, Shanghai University of Finance and Economics, Shanghai, People’s Republic of ChinaCorrespondence: Mengting Zhu, School of Management, Shanghai University, Shanghai, People’s Republic of China, Tel +86-18682641363, Email jocelemy@163.comPurpose: According to the traditional view, “underdog expectations” induce self-doubt in employees, resulting in negative effects. However, a new study suggests that underdog expectations may encourage employees to work harder, resulting in positive effects. Based on regulatory focus theory, this study constructed a moderated double-mediation model to explain the “double-edged sword effect” of underdog expectations.Subjects and Methods: A three-wave survey method and leader–employee pairing method were used to conduct a questionnaire survey among 346 employees drawn from five enterprises in Shanghai, China. Statistical analysis methods, including hierarchical regression analysis, simple slope analysis, and difference analysis, were used for data analysis. SPSS 24.0, Amoss 24.0, and Mplus 7.4 software were employed to test four proposed hypotheses.Results: Under the positive moderating effect of prevention focus, underdog expectations reduce employee work engagement by adopting an avoidance path of employee feedback-avoiding behaviors(β = 0.090, p < 0.01). Moreover, underdog expectations play a negative role in this situation . Under the positive moderating effect of promotion focus, underdog expectations improve employee work engagement by adopting an approach of proving others wrong (β = 0.189, p < 0.001). Moreover, underdog expectations play a positive role in this situation.Conclusion: The study results refined the double-sided effects of underdog expectations on employee work engagement and provided theoretical and practical implications for managers on how to motivate employees with underdog expectations and how to better convey expectations to subordinates.Keywords: underdog expectations, regulatory focus theory, prove others wrong, feedback-avoiding behaviors

Rui Zhao,1 Jianbo Xue,1 Xueli Zhang,1 Maohuan Peng,1 Jing Li,1 Bing Zhou,1 Long Zhao,1 Thomas Penzel,2 Meir Kryger,3 Xiao Song Dong,1 Zhancheng Gao,1 Fang Han1 1Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Sleep Medicine Center, Charité-Universitätsmedizin, Berlin, Germany; 3Division of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USACorrespondence: Xiao Song Dong; Zhancheng Gao, Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, No. 11 Xizhimen Nandajie, Xicheng District, Beijing, 100044, People’s Republic of China, Email dongxiaosong@pkuph.edu.cn; zcgao@bjmu.edu.cnObjective: A novel ring-worn oximeter (Circul) uses reflective photoplethysmography and automated signal processing to calculate oxygen desaturations. We evaluated the ability of Circul to detect obstructive sleep apnea in Chinese adults.Methods: We recruited 207 Chinese Han subjects: 70% males, mean age 48.2± 14.7 years, mean BMI 27.6± 4.8 kg/m2 and mean AHI 28.6± 25.2 events/h. All participants underwent simultaneous polysomnography (PSG) and Circul testing in a sleep laboratory. Oxygen desaturation index (ODI), mean oxygen saturation (MSpO2), cumulative time at SpO2< 90% (CT90), cumulative percentage of sleep time spent with SpO2< 90% (CT90/TST) were derived and compared for the Circul and the PSG.Results: The ODI was 25.3± 24.5 events/h using PSG and 22.2± 24.5 events/h using Circul (P< 0.0001), with an intraclass correlation coefficient (ICC) of 0.884. CT90 and CT90/TST between the two methods were not different; the MSpO2 level calculated by PSG was slightly lower than Circul, 95.0% (93.0– 96.0%) vs 95.3% (93.9– 96.6%), P< 0.0001. Circul-ODI had a good correlation (r=0.91, p< 0.0001) and close agreement with PSG-AHI (Bland-Altman analysis: Mean Difference 6.4, 95% CI − 14.8 to 27.5 events/h). Using a threshold of AHI ≥ 5 events/h, the Circul had 87% sensitivity, 83% specificity, 5.09 positive likelihood ratio (LR+), 86% accuracy, and 0.929 area under the curve (AUC).Conclusion: Circul ring pulse oximetry can detect OSA with reasonable reliability. The Circul system is a reliable and comfortable choice for OSA assessment.Keywords: obstructive sleep apnea, reflective photoplethysmography, pulse oximetry, polysomnography

Zongbo Zhao,&ast; Jianzhong Xue,&ast; Ziliang Zhuo, Wei Zhong, Hui Liu Department of Neurology and Institute of Neurology, The Affiliated Changshu Hospital of Xuzhou Medical University, Suchow, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Liu, Tel/Fax +860512-52925530, Email laoniu20201111@163.comObjective: To investigate the association between IL7R rs6897932 and multiple sclerosis (MS) in southern Chinese people.Methods: In total, 147 MS patients and 530 healthy controls were recruited according to the revised McDonald criteria. The TaqMan method was used for genotyping.Results: With genetic models, we can observe that the additive model, the dominant model, and the recessive model of IL7R rs6897932 were significantly associated with MS [additive model: p=0.032; dominant model (adjusted): p< 0.001, OR=3.61 (95% CI 2.25– 5.83); recessive model (adjusted): p< 0.001, OR=6.80 (95% CI 3.49– 13.89)].Conclusion: Our results suggest that IL7R rs6897932 is associated with MS in a southern Chinese population. More and larger MS studies to explore the genetic risk factors of MS are warranted.Keywords: single-nucleotide polymorphism, multiple sclerosis, IL7R, interleukin

Jiao Xue,1 Qing-Xia Wang,1 Huan-Ming Xiao,2 Mei-Jie Shi,2 Yu-Bao Xie,2 Sheng Li,2 Ming Lin,2 Xiao-Ling Chi2 1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People’s Republic of ChinaCorrespondence: Xiao-Ling Chi, Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Dade Road 111, Guangzhou, 510120, People’s Republic of China, Tel +86+39318398, Fax +86-020-81867705, Email chixiaolingqh@163.comPurpose: Both metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatitis B virus (HBV) are risk factors for hepatocellular carcinoma (HCC). Although concurrent MAFLD is common in patients with HBV-related HCC, whether MAFLD increases the risk of poor prognosis in patients with HBV-related HCC remains unclear. This study aimed to investigate the impact of MAFLD on prognosis in patients with HBV-related HCC.Patients and Methods: In this retrospective cohort study, 549 patients with HBV-related HCC were enrolled from January 2010 to April 2020 in Guangdong Provincial Hospital of Chinese Medicine, including 169 patients with MAFLD (MAFLD group) and 380 patients without MAFLD (Non-MAFLD group). Propensity score matching (PSM) analysis was performed to balance the baseline characteristics. Kaplan–Meier survival curves were performed to compare the prognosis between the two matched groups. A multivariate Cox proportional hazards model was used to determine the risk factors for poor prognosis.Results: The median follow-up time for all patients was 20 (interquartile range 8– 40) months. We found concurrent MAFLD was associated with a significantly decreased PFS rate before and after PSM analysis. The 1-year, 2-year, and 3-year PFS rates for the MAFLD and Non-MAFLD groups after PSM were 61.3% and 70.8%, 43.9% and 54.5%, 31.1% and 41.8%, respectively. Cox multivariable analysis showed that concurrent MAFLD was an independent risk factor for poor prognosis (death or progression) (HR = 1.49, P = 0.001). More interestingly, the risk of poor prognosis was significantly higher in the MAFLD subtype with metabolic components ≥ 2 compared to those with metabolic components < 2 (HR = 1.97, P < 0.001).Conclusion: Concurrent MAFLD was associated with a higher risk of poor prognosis in patients with HBV-related HCC, especially MAFLD with metabolic components ≥ 2.Keywords: hepatocellular carcinoma, hepatitis B virus, metabolic dysfunction-associated fatty liver disease, poor prognosis

Junshuai Xue,1 Nianfeng Sun,2 Yang Liu3 1Department of General Surgery, Qilu Hospital of Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Women’s and Children’s Hospital Affiliated to Qingdao University, Qingdao, 266001, People’s Republic of China; 3Department of General Surgery, Vascular Surgery, Qilu Hospital of Shandong University, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Nianfeng Sun; Yang Liu, Tel +86 18561810688 ; +86 18560088317, Email sunnianfeng@126.com; liuyang_sdu@126.comBackground: Non-healing skin wounds are a common complication in diabetic patients. Vector biomaterials embedded with mesenchymal stem cells (MSCs) are considered a promising treatment approach. In this study, we presented a novel and effective approach to accelerate diabetic skin wound healing.Methods and Materials: Human umbilical cord mesenchymal stem cells (hUC-MSCs) were shaped into spheres. RADA16-I, KLT, and RGD nanopeptides were selected for self-assembly into hydrogels. hUC-MSCs spheroids (hUC-MSCsp) were combined in vitro with self-assembled nanopeptide hydrogels and subsequently transplanted into a mouse model of diabetic skin trauma.Results: Compared with the PBS, hUC-MSCs, hUC-MSCsp, and hUC-MSCs with hydrogel groups, hUC-MSCsp with hydrogel significantly accelerated wound healing (p< 0.01) and shortened the healing time (10 vs 14 vs 21 days). The expressions of IL-6, IL-10, IL-1β, and TNF-α were significantly decreased (p< 0.001). The expression of VEGF was significantly higher in the hUC-MSCsp with hydrogel group (p< 0.05), and the density of neovascularization in the fresh skin tissue at the wound was also remarkably increased (p< 0.01).Conclusion: Nanopeptide hydrogels loaded with hUC-MSCsp accelerated diabetic skin wound healing by inhibiting inflammation and promoting angiogenesis compared with conventional stem cell transplantation, which deserves further investigation.Keywords: diabetic wound, human umbilical cord mesenchymal stem cell, spheroid, nanopeptide hydrogels, treatment

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's

Junshuai Xue,&ast; Jianjun Jiang,&ast; Yang Liu Department of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, Jinan City, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Department of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, No. 107, Road Wen Hua Xi, Jinan City, Shandong Province, 250012, People’s Republic of China, Tel +86 18560088317, Email liuyang_sdu@126.comBackground: Idiopathic hypereosinophilic syndrome (IHES) often causes inflammatory damage to multiple organs. However, whether immune/inflammatory indicators and other factors are associated with mortality in patients with IHES remains unclear.Patients and Methods: The clinical data and follow-up results of 167 patients with IHES were retrospectively analyzed using Cox regression analysis and receiver operating characteristic curve (ROC).Results: Of 167 patients, 120 were men (71.9%) and 47 were women (28.1%). The median age was 52 (36.0, 68.0) years. The median follow-up period was 42.8 (18.5, 75.1) months, during which all-cause mortality occurred in 26 patients (15.6%). Age (HR: 1.041, 95% CI: 1.015– 1.068; p = 0.002), lymphocyte counts (109/L, HR: 0.866, 95% CI: 0.816– 0.907; p = 0.013), platelet counts (109/L, HR: 0.994, 95% CI: 0.989– 0.999; p = 0.012) and NLR (HR: 1.161, 95% CI: 1.054– 1.280; p = 0.003) were independent risk factors for all-cause mortality. There was no relationship between PLR, and SII and all-cause mortality (p = 0.181 and 0.202, respectively). ROC analysis showed that the AUCs of age, lymphocyte count (109/L), platelet count (109/L) and NLR were 0.712 (95% CI: 0.601– 0.824), 0.584 (95% CI: 0.448– 0.719), 0.686 (95% CI: 0.560– 0.812), and 0.797 (95% CI: 0.695– 0.899), respectively, with sensitivities of 0.5, 0.462, 0.769, and 0.792, respectively, and specificities of 0.765, 0.745, 0.617, and 0.845, respectively. Kaplan–Meier analysis (Log rank test) showed that patients with age ≥ 73.5 years, lymphocyte count (109/L) < 1.45, platelet count (109/L) < 225 and NLR ≥ 2.54 had high mortality. Patients with high NLR (≥ 2.54) usually have multiorgan involvement, with cardiac involvement and skin involvement being the most common. Patients with NLR ≥ 2.54 had significantly higher absolute eosinophil counts (p = 0.047) and percentages (p = 0.041).Conclusion: We identified NLR for the first time as an independent predictive factor for all-cause mortality in patients with IHES, necessitating its further application in clinical practice.Keywords: idiopathic hypereosinophilic syndrome, mortality, risk variable, neutrophil/lymphocyte ratio

Dan Li,1,&ast; Xin Zhang,2,3,&ast; Yunzhong Wang,2 Jian Xue,2 Xueqiang Ji,2 Xuejun Shao,2– 4 Yang Li2– 4 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China; 3Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China; 4Clinical Medical College of Pediatrics, Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Li; Xuejun Shao Email 11418092@zju.edu.cn; xjshao@suda.edu.cnObjective: To investigate the epidemiology and drug resistance of pathogens isolated from cerebrospinal fluid samples at a children’s medical center in eastern China and provide the basis for anti-infection treatments.Methods: In all, 307 non-duplicated strains of pathogens were isolated from cerebrospinal fluid samples in the Children’s Hospital of Soochow University from January 2006 to December 2020. Mass spectrometry was used for pathogen identification. The VITEK 2 Compact system and Kirby-Bauer method were applied to determine antimicrobial susceptibility.Results: Among the 307 isolates, gram-positive bacteria, gram-negative bacteria and fungi accounted for 60.26%, 34.53%, and 5.21%, respectively. The most prevalent pathogens were Streptococcus pneumoniae (26.06%), Escherichia coli (20.20%) and Streptococcus agalactiae (17.26%). The number of isolates was highest in winter. The most prevalent gram-positive bacterium in children < 6 months old was Streptococcus agalactiae, while Streptococcus pneumoniae was the most in children were > 6 months old. The drug resistance of gram-positive bacteria, fungi and Haemophilus influenza were not high. In addition, 35 strains of gram-negative bacteria produced extended-spectrum β-lactamases (ESBLs) and 6 strains were identified as multidrug-resistant (MDR) bacteria. These strains showed much higher resistance to the antibiotics than other strains.Conclusion: Cases of meningitis among children have increased in the past 15 years and MDR bacteria were also identified. The emergence of MDR bacteria is a cause for great concern and requires further investigation.Keywords: cerebrospinal fluids, infection, children, drug resistance, epidemiology

Huijie Li,1 Jia Xue,2 Tianjiao Xu,1 Long Wang,1 Liwei Zhang1 1School of Public Administration, Jilin University, Changchun, People’s Republic of China; 2School of Political Science and Law, Northeast Normal University, Changchun, People’s Republic of ChinaCorrespondence: Jia XueSchool of Political Science and Law, Northeast Normal University, Changchun, People’s Republic of ChinaEmail xuej060@nenu.edu.cnPurpose: China’s success in containing the coronavirus is an ongoing process of identifying loopholes and refining the management in the COVID-19 risk chain. This article discusses the role of personal needs in epidemic control and linked psychological needs with management measures to propose intervention advice on curbing viral transmission in a systematic way.Methods: Based on case studies, we showed the integration of the Maslow’s Hierarchy of Needs in the COVID-19 risk chain. The analysis combined the micro-view from individual needs and macro influences from governmental measures. The proposed chain of vulnerabilities could help identify critical links of COVID-19 crisis management in case that cascading effects such as super-spread can be intercepted in time.Results: The article mainly focused on curbing the viral transmission timely whenever cluster of cases resurge. Considering the triggered activities from personal needs may facilitate the spread, minimizing the impact scale while managing the crisis could start with protecting vulnerable population, well governing potential hotspots, and necessary restrictions on group activities. Besides, “individual” protections combined with “institutional” solutions are strongly advocated. The worst scenario would be the governance link slackened or made mistakes, together with delayed identification, plus unprotected way of living and gathering. In order to cut the transmission in time, besides virus-blocking strategies and vaccination approach, screening measures in combination with the satisfaction of personal needs would help identify confirmed cases earlier. Publicizing the model citizen of being responsible could show needs’ satisfaction can live with the virus elimination. At the emergency response stage, it is also crucial to secure fewer loopholes in the health system and strengthen the self-protection barrier by all means.Conclusion: China’s experience offers a reference for the balance between the resurgence of clustered cases and sustained recovery. As long as the global pandemic continues, its impact on personal activities will not stop, and vice versa. The chain of vulnerabilities integrating psychological needs into the COVID-19 risk management can provide clear clues for cutting further transmission in an efficient and more socially acceptable way.Keywords: pandemic control experience, China, COVID-19, risk management

Xu Zhu,1 Jing Xue,2 Zheng Liu,3 Wenjie Dai,4 Hui Xu,5 Qiaoling Zhou,5 Shuangping Zhao,6 Quan Zhou,7 Wenhang Chen5 1Department of Epidemiology and Health Statistics, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Scientific Research, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Anesthesiology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Ji’nan, Shandong, 250014, People’s Republic of China; 4Xiangya School of Public Health, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 5Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 6Department of Intensive Care Unit, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 7Department of Science and Education, The First People’s Hospital of Changde City, Changde, Hunan, 415000, People’s Republic of ChinaCorrespondence: Wenhang ChenDepartment of Nephrology, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of ChinaFax +86 731 84327348Email wenhangchen@csu.edu.cnObjective: The serum lactate/albumin ratio (LAR) can be used to independently predict mortality due to sepsis. However, whether the LAR predicts the outcomes of critically ill patients with acute kidney injury (AKI) remains unclear. This study was performed to assess the prognostic value of the LAR in critically ill AKI patients.Methods: This retrospective observational study enrolled AKI patients, and all data were collected through the eICU Collaborative Research Database. Outcomes included in-hospital and intensive care unit (ICU) death. Multivariate Cox regression analysis was used to determine independent risk factors. Forest plots and smoothing curves were generated. A series of subgroup analyses were performed to further validate the robustness of the findings.Results: A total of 4666 eligible patients were enrolled. We divided the participants into four groups according to the LAR: quartile (Q)1 (LAR < 0.46, n = 1167), Q2 (0.46 ≤ LAR < 0.79, n = 1162), Q3 (0.79 ≤ LAR < 1.49, n = 1170), and Q4 (LAR ≥ 1.49, n = 1167). The LAR, when analyzed as a continuous variable, was associated with hospital and ICU mortality (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18– 1.26, P < 0.0001 for both). The risk of in-hospital and ICU mortality increased with increasing LAR Q relative to Q1. The smoothing curves revealed a continuous linear association after adjusting for all covariates. By the Kaplan–Meier analysis, patients in the higher LAR group showed significantly shorter survival time. By the receiver operating characteristic analysis, LAR was efficient in predicting in-hospital mortality (area under the curve [AUC]: 0.717) and ICU mortality (AUC: 0.733). A positive and consistent effect of the LAR was seen in all subgroups analyses after adjusting for all covariates.Conclusion: A high LAR is an independent risk factor for in-hospital and ICU mortality in critically ill patients with AKI. Further prospective studies are needed to validate these result.Keywords: lactate/albumin ratio, acute kidney injury, mortality, critical care

Junshuai Xue,1,&ast; Delin Ma,2,&ast; Jianjun Jiang,1 Yang Liu1 1Department of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, Jinan City, Shandong Province, People’s Republic of China; 2Department of General Surgery, Shandong University Qilu Hospital, Jinan City, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang LiuDepartment of General Surgery, Vascular Surgery, Shandong University Qilu Hospital, No. 107, Road Wen Hua Xi, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel +86 18560088317Email liuyang_sdu@126.comAbstract: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), has been an important cause of sudden in-hospital death. Studies have shown that the immune/inflammatory response plays an important role in the pathogenesis of vascular disease, with representative markers in the blood including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune/inflammatory index (SII), etc. However, there is a variety of immune/inflammatory indicators. Moreover, most previous studies have been single-center investigations involving one or two indicators, with varying nature of cases, number of cases and study objectives, thereby making it difficult to reach consensus conclusions with good clinical guidelines. This article reviews the clinical value of immunoinflammatory indicators for VTE based on previous studies, including the diagnostic and prognostic capabilities. In conclusion, NLR provides promising predictive capability for the onset and prognosis of VTE and deserves extensive application in clinical practice. PLR also has certain diagnostic and prognostic value, but further studies are warranted to identify its reliability and stability. Monocytes, eosinophils and platelet-related indicators show some clinical association with VTE, although the predictive capabilities are mediocre. SII is of promising potential value for VTE and deserves further investigations. This review will provide new clues and valuable clinical guidance for the diagnosis and therapy of VTE.Keywords: venous thromboembolism, immune/inflammation biomarker, diagnosis, prognosis

Yao Tong,&ast; Chengrong Bao,&ast; Yi-Qiong Xu,&ast; Lei Tao,&ast; Yao Zhou, Lei Zhuang, Ying Meng, Hui Zhang, Jingjing Xue, Weijun Wang, Lele Zhang, Qingbo Pan, Zhenzhen Shao, Tianran Hu, Qian Guo, Qingsheng Xue, Han Lu, Yan Luo Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Luo; Han Lu Email ly11087@rjh.com.cn; luhan0301@163.comBackground: Acute lung injury (ALI) is a severe respiratory disease with high rates of morbidity and mortality. Many mediators regarding endogenous or exogenous are involved in the pathophysiology of ALI. Here, we have uncovered the involvement of integrins and matrix metalloproteinases, as critical determinants of excessive inflammation and endothelial permeability, in the regulation of ALI.Methods: Inflammatory cytokines were measured by quantitative real-time PCR for mRNA levels and ELISA for secretion levels. Endothelial permeability assay was detected by the passage of rhodamine B isothiocyanate-dextran. Mice lung permeability was assayed by Evans blue albumin (EBA). Western blot was used for protein level measurements. The intracellular reactive oxygen species (ROS) were evaluated using a cell-permeable probe, DCFH-DA. Intratracheal injection of lipopolysaccharide (LPS) into mice was conducted to establish the lung injury model.Results: Exogenous MMP-9 significantly aggravated the inflammatory response and permeability in mouse pulmonary microvascular endothelial cells (PMVECs) treated by LPS, whereas knockdown of MMP-9 exhibited the opposite phenotypes. Knockdown of integrin β 3 or β 5 in LPS-treated PMVECs significantly downregulated MMP-9 expression and decreased inflammatory response and permeability in the presence or absence of exogenous MMP-9. Additionally, the interaction of MMP-9 and integrin β 5 was impaired by a ROS scavenger, which further decreased the pro-inflammatory cytokines production and endothelial leakage in PMVECs subjected to co-treatment (LPS with exogenous MMP-9). In vivo studies, exogenous MMP-9 treatment or knockdown β 3 integrin significantly decreased survival in ALI mice. Notably, knockdown of β 5 integrin alone had no remarkable effect on survival, but which combined with anti-MMP-9 treatment significantly improved the survival by ameliorating excessive lung inflammation and permeability in ALI mice.Conclusion: These findings support the β 3/5 integrin-MMP-9 axis as an endogenous signal that could play a pivotal role in regulating inflammatory response and alveolar-capillary permeability in ALI.Keywords: acute lung injury, endothelial cells, integrin, MMP-9

Boyan Liu,1– 3,&ast; Yunbo Xie,2,4,&ast; Jun Chen,4 Junli Xue,1– 3 Xiaoyi Zhang,2 Min Zhao,2 Xiubin Jia,2 Yiwei Wang,4 Shucun Qin1,2 1The Second Affiliated Hospital of Shandong First Medical University, Tai’an, 271000, People’s Republic of China; 2Taishan Institute for Hydrogen Biomedicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai’an, 271000, People’s Republic of China; 3College of Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of General Practice, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shucun QinThe Second Affiliated Hospital of Shandong First Medical University, Tai’an, 271000, People’s Republic of ChinaTel/Fax +86 538 6222986Email scqin@sdfmu.edu.cnYiwei WangDepartment of General Practice, The Affiliated Hospital of Chengde Medical University, Chengde, 067000, People’s Republic of ChinaTel/Fax +86 314 2279511Email chengdewyw@126.comBackground: Molecular hydrogen (H2) has been recognized as an effective antioxidant with no or little side effects. While it is known that oxidative stress is closely associated with aging, the beneficial effect of H2 on oxidative stress-related aging is still unclear. In this study, a mouse model of D-galactose-induced aging was employed to investigate the protective effects of H2.Methods: The mice were administrated of H2 via different routes (4% H2 inhalation, H2-rich water drinking, and H2-rich saline injection), the aging-related biomarkers in plasma and the oxidative stress in different tissues were measured.Results: The results showed that H2 improved aging-related biomarkers, ie, total antioxidant capacity, advanced glycation end products, tumor necrosis factor-α, free fatty acids, and alanine aminotransferase in plasma. Furthermore, H2 alleviated oxidative stress in the liver, brain, and heart by reducing the levels of lipid peroxidation and malondialdehyde and increasing the activity of superoxide dismutase. In addition, it seems that 4% H2 inhalation was the most effective regarding the amount of H2 taken up and in reducing the markers of oxidative stress in some of the tissues; however, the other routes of administration resulted in the same efficacy in most indicators.Conclusion: H2 can prevent oxidative stress in D-galactose-induced aging mice when administered by different routes.Keywords: molecular hydrogen, administration routes, oxidative stress, aging, D-galactose

Yang Li,1– 4,&ast; Dan Li,5,&ast; Jian Xue,4 Xueqiang Ji,4 Xuejun Shao,4 Jie Yan1– 3 1Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, People’s Republic of China; 3Division of Basic Medical Microbiology, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China; 4Department of Clinical Laboratory, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of China; 5Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie YanDepartment of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, 866 Yu-Hang-Tang Road, Hangzhou, Zhejiang, 310058, People’s Republic of ChinaTel +86-571-88208297Fax +86-571-88208294Email Med_bp@zju.edu.cnXuejun ShaoDepartment of Clinical Laboratory, Children’s Hospital of Soochow University, 92 Zhong-Nan Street, Suzhou, Jiangsu, 215025, People’s Republic of ChinaTel +86-512-80691203Email xjshao@suda.edu.cnObjective: This study investigated the epidemiology, virulence and drug resistance of invasive Klebsiella pneumoniae (K. pneumoniae) isolates at a children’s medical center in eastern China in order to obtain epidemiologic, virulence, and antimicrobial resistance data that can guide for the selection and development of anti-infection treatments.Methods: A total of 94 invasive K. pneumoniae strains were isolated from children between January 2016 and December 2020 at the Children’s Hospital of Soochow University. The strains were identified by mass spectrometry. The Kirby–Bauer method and VITEK 2 Compact system were used to analyze the antimicrobial susceptibility. Polymerase chain reaction (PCR) and sequencing was performed to detect the capsular serotypes, virulence-associated genes, β-lactam antibiotic resistance genes and multilocus sequence typing.Results: The PCR results showed that 87 strains (92.55%) of invasive K. pneumoniae were hypervirulent capsular serotypes, with K57 as the dominant capsular serotype (62.77%). All strains carried virulence-associated genes. Among them, 84 strains (89.36%) carried hypervirulence genes, with iroB (86.17%) being the predominant; meanwhile, other virulence genes, including wabG (100.00%), mrkD (98.94%), ycfM (96.81%), fimH (95.74%) and Uge (88.30%), were detected in most strains. All strains carried β-lactam antibiotic resistance genes; the main extended-spectrum β-lactamase gene was blaSHV-11 (86.17%) and the major AmpC cephalosporinase genes were blaFOX-1 (86.17%) and blaACT-1 (70.21%). Carbapenemase genes were detected in only a few isolates. Notably, 12 invasive K. pneumoniae isolates were identified as carbapenem-resistant and hypervirulent K. pneumoniae (CR-HVKP), and 14 other multidrug resistance (MDR) isolates were also detected.Conclusion: The results of this study reveal the epidemiology, virulence and antimicrobial resistance of invasive K. pneumoniae in pediatric patients. Both CR-HVKP and MDR strains were identified, which should be of great concern to clinicians.Keywords: Klebsiella pneumoniae, invasive infection, children, virulence factors, resistance genes

Min Wu,1,&ast; Xiaohao Zhang,2,&ast; Jingjing Chen,3,&ast; Mingming Zha,4 Kang Yuan,5 Kangmo Huang,2 Yi Xie,2 Jianzhong Xue,6 Xinfeng Liu1,2,7 1Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, 210002, People’s Republic of China; 2Department of Neurology, Jinling Hospital, Affiliated Medical School of Nanjing University, Nanjing, 210002, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, 200433, People’s Republic of China; 4Department of Neurology, Jinling Hospital, Medical School of Southeast University, Nanjing, 210002, People’s Republic of China; 5Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, 210000, People’s Republic of China; 6Department of Neurology, Changshu No.2 People’s Hospital, Changshu, People’s Republic of China; 7Stroke Center & Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng LiuDepartment of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, No. 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210002, People’s Republic of ChinaTel +86 138 13835114Email xfliu2@vip.163.comJianzhong XueDepartment of Neurology, Changshu No.2 People’s Hospital, No. 18 Taishan Road, Changshu, Jiangsu Province, People’s Republic of ChinaTel +86 13506247572Email xjz2021@sina.comBackground and Purpose: The impact of low-grade inflammation (LGI) on stroke recurrence has not been well studied yet. We aimed to evaluate the association between LGI and stroke recurrence in patients with ischemic stroke.Methods: Patients with first-ever ischemic stroke diagnosed within 72 hours of symptoms onset were consecutively recruited from the Nanjing Stroke Registry Program. C-reactive protein (CRP) level, white blood cell (WBC) count, platelet (PLT) count, and neutrophil-to-lymphocyte ratio (NLR) were conceived as low-grade inflammation biomarkers and combined into a standardized LGI score. The association of LGI score with the risk of stroke recurrence was analyzed with multivariate Cox regression models. Analyses accounting for the competing risk of stroke recurrence and death were also performed.Results: Of the 1214 patients studied (median age, 61 years; male, 71.6%), 177 (14.6%) patients experienced a recurrent stroke with a median follow-up of 23.0 (interquartile ranges, 14.5– 34.0) months. Patients with stroke recurrence had a higher LGI score (median, 3 versus − 2; P < 0.001) than those without recurrence. The univariate analysis indicated that patients with LGI scores in the fourth quartile were more likely to have a stroke recurrence (hazard ratios [HR], 4.312; 95% confidence interval [CI], 2.675– 6.952; P < 0.001). After adjusting for potential confounders, the association remained significant in the multivariate Cox regression model (HR, 4.080; 95% CI, 2.420– 6.879; P < 0.001). Competing risks model and sensitivity analysis further confirmed this conclusion.Conclusion: This study showed that an elevated LGI score was associated with a higher risk of stroke recurrence, independent of other vascular risk factors.Keywords: low-grade inflammation, stroke recurrence, ischemic stroke, predictor