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Hongjuan Jiang, Xiangyu Chi, Yanhong Sun, Hongwen Li Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Hongwen Li, Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Email lihongwen_91@163.comBackground: Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models.Methods: The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis.Results: The serum concentration of VDBP was significantly higher in COVID-19 with ALI (P < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (r=0.329, P = 0.002), c-reaction protein (r = 0.470, P < 0.001), serum amyloid A (r = 0.900, P < 0.001), procalcitonin (r = 0.670, P < 0.001), and interleukin 6 (r = 0.452, P < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001– 1.006, P = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1β and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group (P < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced (P < 0.05).Conclusion: In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.Keywords: Vitamin D binding protein, COVID-19, acute lung injury, pathogenesis

Yan Liu,1 Xinli Chi,2,3 Xuemin Xin4 1School of Media and Communication, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 3The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 4School of Communication and Media, Guangzhou Huashang College, Guangzhou, 511300, People’s Republic of ChinaCorrespondence: Xuemin Xin, School of Communication and Media, Guangzhou Huashang College, Guangzhou, 511300, People’s Republic of China, Tel +86 13178879558, Email cindy05rz@163.comBackground: Digital hoarding has emerged as a pervasive psychological phenomenon and behavioral challenge among contemporary youth. This study focused on exploring the relationship between upward social comparison via social media, fear of missing out (FoMO), mindfulness, digital hoarding behavior, and its underlying mechanisms.Methods: A total of 927 young people participated in this cross-sectional study. Research instruments included the Social Comparison Scale, the Fear of Missing Out Scale, the Mindfulness Measure, and the Digital Hoarding Behavior Questionnaire. The data analysis comprised descriptive statistics and correlation analyses. Advanced analyses were conducted using Model 4 for mediation and Model 8 for moderation from the PROCESS macro.Results: (1) Upward social comparison via social media was a strong predictor of digital hoarding behavior, even after controlling for variables such as gender, age, and education. (2) FoMO mediated the relationship between upward social comparison via social media and digital hoarding. (3) Mindfulness moderated both the direct effect of upward social comparison via social media on digital hoarding and the first segment of the mediating role of FoMO.Discussion: The study further clarified the antecedents and psychological mechanisms that drive digital hoarding behavior. The findings contribute new perspectives for understanding the emerging concept of digital hoarding, while providing empirical evidence and valuable guidance for encouraging young adults to use social media responsibly and reduce impulsive hoarding tendencies.Keywords: social media, digital hoarding, upward social comparison via social media, fear of missing out, mindfulness

Xiaobo Chi Conservatory of Music, Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Xiaobo Chi, Tel +86 15313297280, Email chixb1121@163.comPurpose: We developed a research framework based on the community of inquiry theory to examine the relationship between three kinds of MOOC presence (teaching presence, social presence, and cognitive presence) and learning engagement. Further, we explored the mediating effect of autonomous motivation and the moderating role of grit in this relationship.Participants and Methods: The online survey included a sample of N = 794 college students (46.473% male) between the ages of 18 and 20. The COI survey instrument, short grit scale, the Utrecht work engagement scale-student scale and academic self-regulation questionnaire were used to test hypotheses.Results: The study results showed that all three MOOC presences (teaching presence, social presence, and cognitive presence) had significant positive relationship with learning engagement. Autonomous motivation had a mediating role in them. Also, the positive relationship between social presence, cognitive presence, and autonomous motivation was stronger for students with a higher level of grit.Conclusion: This study enriches the literature on whether and how the presence knowledge of MOOC courses affects college students’ learning engagement, and the complexity of MOOC environments determines that grit plays an indispensable role in the learning process.Keywords: MOOC, community of inquiry, presence, learning engagement, grit

Liqing Yao,1,2 Kaixin Liang,3,4 Qiu Zhang,5 Xinli Chi3,4 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Faculty of Medicine, Medical Sciences Division, Macau University of Science and Technology, Macau, People’s Republic of China; 3School of Psychology, Shenzhen University, Shenzhen, People’s Republic of China; 4The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen University, Shenzhen, People’s Republic of China; 5The Center for Health Economics and Health Promotion Research, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Qiu Zhang, The Center for Health Economics and Health Promotion Research, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email zhangqiu@gdpu.edu.cn Xinli Chi, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xinlichi@szu.edu.cnPurpose: This study aimed to evaluate the associations between unhealthy eating habits and insomnia symptoms with Internet addiction (IA) among Chinese left-behind children (LBC) based on potential gender difference.Methods: This cross-sectional study was conducted in junior high schools from an economically disadvantaged area of China in May 2020. Participants were asked to complete the information and scales of socio-demographic characteristics, eating habits (the frequency of eating carbohydrates, fruits, vegetables, protein, and breakfast), insomnia severity and IA. A total of 3156 LBCs (43.9% males and 56.1% females, aged 14.2 years in average) were used for final analyses. Associations between eating habits and insomnia symptoms with IA were analyzed by generalized linear model with binary logistic regression.Results: The study found that left-behind children (LBCs) had unhealthy eating habits, particularly among females. Females reported more insomnia symptoms than males. The prevalence of IA was similar across genders. Consuming fewer fruits and vegetables and skipping breakfast were linked to increased IA risk, especially in females. Insomnia was significantly associated with higher IA risk in both genders.Conclusion: In LBCs, unhealthy eating and sleep were notably linked to IA, especially in females. Addressing these factors might reduce the prevalence of IA among LBCs.Keywords: eating habits, insomnia, Internet addiction, left-behind children, gender difference

Yukun Feng,1,2,&ast; Na Ni,3,&ast; Wei Liu,4 Xinli Chi5,6 1Shenzhen Audencia Financial Technology Institute, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Faculty of Business Administration, University of Macau, Macau, People’s Republic of China; 3Faculty of Business, Lingnan University, Hong Kong, People’s Republic of China; 4School of Management, Xiamen University, Xiamen, 361005, People’s Republic of China; 5School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 6The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Chi, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Tel +86 755 26976348, Email xinlichi@126.comPurpose: Past studies have indicated that air pollution is a major environmental factor that negatively affects prosocial behavior in adolescents. However, the mechanism underlying this negative relationship has not been fully explored. This study postulated that this impact may occur through individual resilience, a major psychological capital for adolescents. In addition, we studied interpersonal relations, namely, adolescents’ perceived family and teacher support, which may moderate the proposed relationship.Methods: This study combined the three-year tracking survey data of 11-to-15 old adolescents (N=1301; approximately 48% female) in China with objective data from the air quality index (AQI) to measure the level of air pollution.Results: Findings from ordinary least squares analysis indicated that air pollution negatively influences adolescents’ prosocial behavior, and their resilience mediates this negative relationship. In addition, the results showed that the negative effect of air pollution on adolescent resilience is attenuated by higher family income, whereas it is accentuated by the absence of teacher support.Conclusion: Our study provides insight into how the negative effect of air pollution on adolescents’ prosocial behavior is mediated by their psychological resilience, and highlights the moderating role of adolescents’ interpersonal relations in the association between air pollution and their psychological resilience. Our research also provides practical advice on how families, teachers, and psychologists can mitigate this negative impact.Keywords: psychological resilience, environment, interpersonal relations, prosocial behavior, adolescents, China

Xiaolei Chi,1,2,&ast; Shushu Yu,1,2,&ast; Kun Zhu,3 Yiyao Chen,1,2 Yi Chu,1,2 Xinliang Chen1,2 1Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Embryo Original Disease, Shanghai, People’s Republic of China; 3Department of Pathology, Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinliang Chen, Tel +8618017316169, Fax +86(21)64071243, Email superstarcxl@126.comPurpose: This study sought to explore the obstetric factors affecting early postpartum pelvic floor function of primiparas after vaginal delivery.Patients and Methods: We included 3362 primiparas who underwent postpartum re-examination in International Peace Maternity and Child Health Hospital at 42– 60 days after delivery. The Glazer Protocol was used to evaluate their pelvic floor function, and univariate and multivariate logistic regression analyses were performed to identify obstetric factors that might affect it.Results: Forceps-assisted delivery significantly increased the risk of the decline in fast- and slow-twitch muscle strength in the early postpartum period when compared with natural vaginal delivery (P < 0.05). Women with a pre-pregnancy body mass index (BMI) of ≥ 18.5 kg/m2 had a decreased risk of decline in fast-twitch muscle strength than those with a pre-pregnancy BMI of < 18.5 kg/m2 (P < 0.05). Women who had a pre-pregnancy BMI of 24.0 to < 28.0 kg/m2 bore a decreased risk of decline in slow-twitch muscle strength than those with a pre-pregnancy BMI of < 18.5 kg/m2 (P < 0.05). The risk of decline in fast-twitch muscle strength and slow-twitch muscle in women with anemia during pregnancy was significantly increased (P < 0.05); women with second-stage labors of > 2 h had an increased risk of fast-twitch and slow-twitch muscle strength decline than those with < 2 h (P < 0.05).Conclusion: Both pre-pregnancy underweight and obesity may cause impairment of early postpartum pelvic floor function. Forceps delivery, anemia during pregnancy, and the length of second stage of labor are independent factors leading to pelvic floor function impairment.Keywords: surface electromyography, Glazer Protocol, anemia during pregnancy, forceps delivery, the second stage of labor, body mass index

Huiqiong Liu,1 Dao Wang,1 Miaomiao Tang,1 Peisheng Jia,1 Yufeng Huo,1 Erhu Wei,1 Hao Xu,2 Xiaohui Chi,2 Huaili Wang1 1Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Huaili Wang, Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu East Zhonghuan Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-371-66271057, Email whlek6527@126.comPurpose: With the spread of multiple drug-resistant bacteria, blaNDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of blaNDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both blaNDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We isolated an E. hormaechei strain DY1901 carrying both blaNDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying blaNDM-1 was 45Kb in length and belonged to IncX3.Conclusion: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.Keywords: E. hormaechei, New Delhi metallo-β-lactamase, mcr-9, whole-genome sequencing, phylogenetic analysis

Shuguang Xu,1 Jinjing Tu,1 Liang Zhang,1 Yinv Chen,1 Xiaoqi Dong,1 Xiaohui Chi,2,&ast; Hao Xu2,&ast; 1Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Xu; Xiaohui Chi, Email xuhao930523@163.com; chixiaohui@zju.edu.cnPurpose: Nosocomial infections caused by New Delhi metallo-β-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene blaNDM-1 and also have antibiotic resistance genes such as β-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship.Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded blaNDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.Keywords: Aeromonas caviae, New Delhi metallo-β-lactamase, whole-genome sequencing, SNP, phylogenetic analysis

Chunbo Kang, Jie Zhang, Shiyang Hou, Jinlei Wang, Xubin Li, Xiaowei Li, Xiaoqian Chi, Haifeng Shan, Qijun Zhang, Tiejun Liu General Surgery Department, Beijing Rehabilitation Hospital of Capital Medical University, Beijing, 100144, People’s Republic of ChinaCorrespondence: Tiejun Liu, General Surgery Department, Beijing Rehabilitation Hospital of Capital Medical University, Xixiazhuang, Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel/Fax +86 10 5698 1152, Email liutjdoc@163.comObjective: This study aimed to investigate the value of combining percutaneous transhepatic gallbladder drainage (PTGD) with gallbladder-preserving cholecystolithotomy (GPC) in high-risk patients with acute calculous cholecystitis.Methods: Clinical data from 74 high-risk patients with acute calculous cholecystitis, admitted to our hospital between October 2018 and September 2021, were analyzed retrospectively. All the patients underwent PTGD, and 59 of them underwent delayed cholecystectomy, while 14 patients were subjected to GPC 8– 12 weeks after the PTGD; one patient, whose life expectancy was fewer than 6 months, was not treated for gallstones after PTGD.Results: In all 74 patients, symptom remission was achieved after the PTGD therapy, and the incidence of catheter-related complications was 10.8%. Among the 59 patients who underwent delayed cholecystectomy (DC) after PTGD, there was a complication incidence of 6.8%. Of the 14 patients who underwent GPC after the PTGD, 13 patients were subjected to the removal of drainage tubes, 1 patient received cholecystostomy catheter draining externally, and two patients (14.3%) had complications. There were no perioperative deaths.Conclusion: Percutaneous transhepatic gallbladder drainage, combined with GPC, is a safe and effective treatment that is suitable for high-risk patients with acute calculous cholecystitis who cannot receive DC. This combined method allows for early acute cholecystitis to settle, helps to remove gallstones at a later stage, and solves the problem of long-term tube drainage after PTGD.Keywords: percutaneous transhepatic gallbladder drainage, PTGD, gallbladder-preserving cholecystolithotomy, GPC, high-risk acute calculous cholecystitis

Liuyue Huang,1,&ast; Kaixin Liang,1,&ast; Si-Tong Chen,2 Yizhen Ren,3 Yi Zhu,4 Xinli Chi1 1School of Psychology, Shenzhen University, Shenzhen, 518061, People’s Republic of China; 2Institute for Health and Sport, Victoria University, Melbourne, 8001, Australia; 3Beijing Key Laboratory of Applied Experimental Psychology, Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China; 4School of Early-Childhood Education, Nanjing Xiaozhuang University, Nanjing, 211171, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhu; Xinli Chi Email 16187654@qq.com; xinlichi@szu.edu.cnBackground: Physical activity and self-compassion are closely related to individuals’ mental health (eg, depression). However, most studies only examined their independent roles in mental health without considering the potential interaction between the two variables. The present study aimed to investigate the independent and joint associations between physical activity (PA) and self-compassion (SC) on depression symptoms and examine the additive interaction between PA and SC.Methods: A cross-sectional design was utilized in the present descriptive study. By recruiting participants via social media platforms, 1846 Chinese college students completed International Physical Activity Questionnaire Short Form, the Self-Compassion Scale-Short Form, the 9-item Patient Health Questionnaire, and items regarding socio-demographic information. Independent and joint roles of low-level PA (LPA) and low-level SC (LSC) on depression symptoms were examined by logistic regression models. Additive interaction between LPA and LSC on depression symptoms was examined by the following indices: relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). Socio-demographic variables were included in the models as covariates.Results: Both LPA (OR = 1.47 [1.16, 1.86]) and LSC (OR = 5.74 [3.89, 8.45]) were independently associated with higher probability of depression symptoms. Combining LPA and LSC led to an additive interaction and greatly increased the odds of depression symptoms (OR = 9.62 [5.38, 17.22]; RERI = 2.47 [0.19, 4.75], AP = 0.25 [0.05, 0.44], S = 1.38 [1.02, 1.87]).Conclusion: Both LPA and LSC were associated with an increased risk of depression symptoms. Moreover, combining LPA and LSC may develop an additive risk for depression symptoms. Future research and clinical intervention could integrate PA and SC to find a better way to resist depression symptoms.Keywords: physical activity, self-compassion, depression, interaction, college students

Xiumin Cui,1,2 Xinli Chi3 1College of Education for the Future, Beijing Normal University, Zhuhai, 519087, People’s Republic of China; 2The Affiliated Kindergarten of Meilian Primary School, Shenzhen, 518035, People’s Republic of China; 3School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of ChinaCorrespondence: Xinli ChiSchool of Psychology, Shenzhen University, 1688 Nanhai Avenue, Nanshan District, Shenzhen, Guangdong Province, People’s Republic of ChinaEmail xinlichi@126.comIntroduction: Lockdowns and online homeschooling during the COVID-19 coronavirus pandemic have significantly increased Internet use and adolescents’ risk of developing or reinforcing related addictive behaviors. While various theoretical propositions have suggested that social support, resilience, and post-traumatic stress disorder (PTSD) symptoms can predict Internet addiction, no study has yet examined the combined influence of these factors on Internet addiction. This study therefore aimed to investigate the mediating roles of resilience and PTSD symptoms in the relationship between perceived social support and the Internet addiction of Chinese adolescents in the context of COVID-19.Methods: This study included 2544 adolescents living in the south China city of Qinzhou. The participants completed a self-report questionnaire one week before their return to classes after homeschooling. To examine whether resilience and PTSD symptoms mediated the relationship between social support and Internet addiction, we performed serial mediation analysis using the Model 6 PROCESS macro developed by Hayes (2013).Results: Social support was negatively and directly associated with Internet addiction and indirectly via resilience, PTSD symptoms, and by the multiple mediation of resilience to PTSD symptoms.Discussion: The results of this study suggest that, to address Internet addiction, it may be more effective to focus not on addictive behaviors themselves but on individuals’ existing mental health. It is important to provide adequate social support to improve the resilience of adolescents, thereby reducing PTSD symptoms and Internet addiction.Keywords: social support, resilience, PTSD symptoms, Internet addiction, COVID-19 pandemic, adolescents

Kang C, Zhang J, Hou S, et al. J Inflamm Res. 2022;15:2901–2910. The authors have advised an error was made in the author list on page 2901, specifically, the indication of which authors contributed equally to this work. The correct author list and affiliations are as follows. Chunbo Kang,* Jie Zhang,* Shiyang Hou, Jinlei Wang, Xubin Li, Xiaowei Li, Xiaoqian Chi, Haifeng Shan, Qijun Zhang, Tiejun Liu General Surgery Department, Beijing Rehabilitation Hospital of Capital Medical University, Beijing, 100144, People’s Republic of China *These authors contributed equally to this work The authors apologize for this error.

Ganfeng Liang,1,&ast; Yuting Rao,2,3,&ast; Shuang Wang,4 Xiaohui Chi,2 Hao Xu,2 Yang Shen1 1Department of Infectious Diseases, The First Hospital of Taizhou, Taizhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, Puyang Oil Field General Hospital, Puyang, People’s Republic of China; 4Institute of Bacterial Infection Disease Control, Shandong Centre for Disease Control and Prevention, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen; Hao Xu Email Shenyanghtt@163.com; xuhao0523@zju.edu.cnBackground: The emergence of the plasmid-borne colistin-resistant gene (mcr-1) poses a great threat to human health. What is worse, the recent observations of the coexistence of mcr-1 with carbapenemase encoding genes in some bacteria caused even more concern. Yet, there is a lack of observations of such strains in the human gut.Methods: The isolation of E. coli L889 was performed on selective medium plates. Antibiotic susceptibilities were determined by an agar dilution and a broth microdilution method. Multi-locus sequence typing (MLST) and acquired resistance genes were also characterized. Transferability of blaNDM-9/mcr-1-carrying plasmids was determined by conjugation, replicon typing and S1-Pulsed-field gel electrophoresis (S1-PFGE), and Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Novaseq and Nanopore platforms.Results: E. coli L889 was identified as ST1101 concomitantly carrying blaNDM-9 and mcr-1 from a stool sample. Antimicrobial susceptibility tests showed that it was resistant to various antimicrobial agents and only susceptible to tigecycline. Notably, blaNDM-9 was located on a ∼ 114-kb untypable plasmid, while mcr-1 was located on a ∼ 63-kb IncI2 plasmid.Conclusion: Our research, to our knowledge, first reported an ST1101 E. coli strain with an untypeable blaNDM-9-harbouring plasmid and an IncI2 mcr-1-carrying plasmid. The colonized E. coli strains potentially contribute to the dissemination and transfer of blaNDM-9 and mcr-1 to clinical isolates, which is a considerable threat to public health and should be closely monitored.Keywords: blaNDM-9, mcr-1, gut, Escherichia coli, ST1101

Xiangqian Guan, Yuyan Lu, Heping Zhu, Shuqi Yu, Wenxiu Zhao, Xiaoqin Chi, Chengrong Xie, Zhenyu Yin Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Chengrong Xie; Zhenyu YinDepartment of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, 209 South Hubin Road, Xiamen, Fujian Province, 361004, People’s Republic of ChinaEmail eason_xiecr@126.com; yinzy@xmu.edu.cnBackground: Emerging evidences have highlighted the roles of neutrophils, as the major host microenvironment component, in the development of hepatocellular carcinoma (HCC). Neutrophils extracellular traps (NETs) produced in the infection can strengthen the behavior of cancer metastasis. Here, we investigated the roles of NETs in HCC metastasis and further explore the underlying mechanism of how NETs interact with cancer.Methods: The neutrophils were isolated from whole blood of HCC patients and used to evaluate the formation of NETs. NET markers were detected in tissue samples, plasma and cell climbing slice. Mouse models were used to evaluate the roles of NETs in HCC metastasis in vivo, and the corresponding mechanisms were explored using in vivo and in vitro assays.Results: An increase in the release of NETs in patients with HCC, particularly those with portal vein tumor thrombosis (PVTT). The presence of NETs in HCC tumor tissues closely correlated with a poor prognosis. Functionally, the invasion ability of HCC cells was enhanced by co-culture with HCC neutrophils, through NETs formation, while the neutrophils from a healthy donor (HD) exhibited the inhibition of the invasion ability. Furthermore, we observed an enhanced ability of forming NETs in neutrophils from HCC patients in vitro, especially patients with PVTT or extra-hepatic metastasis. An in-vivo animal study demonstrated that neutrophils of HCC facilitated the metastatic behavior towards the lung. The further mechanistic investigation unveiled that HCC cells-derived cytokine IL-8 triggered NETs formation in an NADPH oxidase-dependent manner, and NETs-associated cathepsin G (cG) promoted HCC metastasis in vitro as well as vivo. Clinically, the expression of the cG protein in tumor tissues displayed a close correlation with the disease prognosis of HCC patients.Conclusion: Our findings implicated that the induction of NETs by HCC cells is a critical metastasis-supporting cancer–host interaction and that NETs may serve as an immune-based potential therapeutic target against HCC progression.Keywords: hepatocellular carcinoma, neutrophils extracellular traps, cathepsin G, IL-8, E-cadherin, metastasis, NADPH

Weijie Cao,1,* Lina Guan,1,* Xiaoning Li,1 Ran Zhang,1 Li Li,1 Suping Zhang,1 Chong Wang,1 Xinsheng Xie,1 Zhongxing Jiang,1 Dingming Wan,1 Xiaohui Chi2 1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijie Cao Email caoweijie2003@126.comPurpose: To explore the epidemiological characteristics and risk factors of bloodstream infections (BSI) in patients who develop agranulocytosis fever after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study also provides a basis for the clinical treatment of BSI.Methods: A retrospective analysis of 397 allo-HSCT patients in the Department of Hematology of our hospital was conducted from January 2013 to December 2017 to analyze the incidence of BSI, the distribution and types of pathogenic bacteria, and drug resistance rates. We also determined whether various parameters are risk factors to BSI, including the patient age, gender, disease type, transplantation method, stem cell source, pre-treatment with anti-thymocyte globulin (ATG), and agranulocytosis time.Results: Among the 397 allo-HSCT patients, 294 had a fever during the period of agranulocytosis, and 52 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 17.7% (52/294). Among the 60 pathogens detected, 43 (71.67%), 10 (16.67%), and 7 (11.67%) were Gram negative strains, Gram positive strains, and fungi, respectively. The most common bacteria were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The detection rate of extended-spectrum β-lactamase (ESBL) was 40.0%, and carbapenem-resistant Enterobacteriaceae (CRE) accounted for 17.9%. Single-factor and multi-factor analyses showed that pre-treatment with ATG, agranulocytosis time (≥ 21 days), and stem cell source were risk factors for BSI.Conclusion: We found that in our hospital, BSIs in allo-HSCT patients are mainly caused by Gram-negative bacteria, and the resistance rate to carbapenem drugs is high. Pre-treatment with ATG, agranulocytosis time (≥ 21 days), and stem cell source are risk factors for BSI.Keywords: hematopoietic stem cell transplantation, agranulocytosis, BSI, pathogenic bacteria, risk factors

Chunping Lu,1,* Xinli Chi,2,* Kaixin Liang,2 Si-Tong Chen,3 Liuyue Huang,2 Tianyou Guo,2 Can Jiao,2 Qian Yu,4 Nicola Veronese,5 Fernanda Cunha Soares,6 Igor Grabovac,7 Albert Yeung,8 Liye Zou4 1The Greater Bay Area Institute of Educational Research, Shenzhen University, Shenzhen 518060, People’s Republic of China; 2Center for Lifestyle and Mental Health, Shenzhen University, Shenzhen 518060, People’s Republic of China; 3Institute for Health and Sport, Victoria University, Melbourne 8001, Australia; 4Exercise and Mental Health Laboratory, Shenzhen University, Shenzhen 518060, People’s Republic of China; 5Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy; 6School of Physical Education, University of Pernambuco, Recife, PE, Brazil; 7Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Wien 1090, Austria; 8Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA*These authors contributed equally to this workCorrespondence: Liye ZouExercise and Mental Health Laboratory, Shenzhen University, Shenzhen 518060, People’s Republic of ChinaTel +86 188-2343-7684Email liyezou123@gmail.comPurpose: This study aimed to investigate associations of physical activity time (PAT) and sitting time (ST) independently and jointly with insomnia, depressive and anxiety symptoms among Chinese adolescents in the context of COVID-19.Methods: A cross-sectional study including 965 adolescents (mean age = 15.26, SD = 0.46) was conducted in May 2020. PAT, ST and the symptoms of insomnia, depression and anxiety were assessed with the International Physical Activity Questionnaire Short Form, the Youth Self-Rating Insomnia Scales, the 9-item Patient Health Questionnaire and the Generalized Anxiety Disorder scale via an online survey platform. Logistic regression was used to analyze the association between COVID-19-related fear, PAT, ST and combinations of PAT and ST with insomnia, depressive and anxiety symptoms.Results: COVID-19-related fear was associated with higher odds of insomnia, depressive and anxiety symptoms. PAT was associated with lower odds of insomnia and depressive symptoms, while ST was associated with higher odds of these three symptoms. After combining PAT and ST, the group with both low PAT and high ST was set as the referent. For insomnia, groups with low ST reported significantly lower odds of symptoms. For depression, groups with high PAT and/or low ST reported lower odds of symptoms. Regarding anxiety, only the group with both high PAT and low ST reported lower odds of symptoms. Generally, group with both high PAT and low ST reported lower odds of the three symptoms than the referent.Conclusion: COVID-19-related fear was a risk factor for developing insomnia, depressive and anxiety symptoms among Chinese adolescents. Fortunately, moving more and sitting less were good for sleep and mental health in Chinese adolescents during the pandemic. Educators should help adolescents to be more physically active in their daily life in the primary prevention of adolescent insomnia, depression and anxiety.Keywords: exercise, physical activity, sedentary behavior, sleep, mental health

Lei Song,1,2 Yi Luo,1 Shaoling Li,2 Ming Hong,1 Qi Wang,1 Xiaoling Chi,2 Cong Yang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People’s Republic of ChinaCorrespondence: Cong Yang; Xiaoling ChiScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of ChinaTel +86 15625016580Email yangcong303@163.com; chixiaolingqh@163.comAims: Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC).Purpose: In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells.Results: We found that ISL inhibited cell viability and proliferation and induced apoptosis in a dose- and time-dependent manner in liver cancer lines. Furthermore, ISL could activate autophagy in HCC cells, and the autophagy inhibitor HCQ enhances ISL-induced apoptosis in HCC cells. Additionally, ISL induced apoptosis and autophagy through inhibition of the PI3K/Akt/mTOR pathway. Most importantly, in a xenograft tumor model in nude mice, data showed that the administration of ISL decreased tumor growth and concurrently promoted the expression of LC3-II and cleaved-caspase-3. Interestingly, we found that ISL inhibits mTOR by docking onto the ATP-binding pocket of mTOR (ie, it competes with ATP). We thus suggest that mTOR is a potential target for ISL inhibition of hepatocellular carcinoma development, which could be of interest for future investigations.Conclusion: Taken together, the results reveal that ISL effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction in vivo and in vitro, probably via the PI3K/Akt/mTOR pathway. ISL may be a potential therapeutic agent for hepatocellular carcinoma.Keywords: isoliquiritigenin, hepatocellular carcinoma, apoptosis, autophagy, mTOR

Miaoxia Liu,1,2,* Ruihong Wu,1,3,* Xu Liu,1 Hongqin Xu,1 Xiumei Chi,1,3 Xiaomei Wang,1 Mengru Zhan,1 Bao Wang,1 Fei Peng,1 Xiuzhu Gao,1,3 Ying Shi,1 Xiaoyu Wen,1 Yali Ji,2 Qinglong Jin,1 Junqi Niu1 1Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Phase I Clinical Research Center, First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinglong JinDepartment of Hepatology, First Hospital of Jilin University, 71 Xin Min Street, Changchun 130021, People’s Republic of ChinaTel/Fax +86-431-81875103Email jinql2016@163.comPurpose: GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC.Patients and Methods: We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD). We also collected 50 patients with other malignant liver tumors (OMTs) and 50 healthy controls (HCs). A test dataset (169 patients with HCC and 139 with CLD) was used to test the performance of GAAP.Results: The GALAD-C and GAAP models achieved comparable performance (area under the receiver operating characteristic curve [AUC], 0.922 vs 0.914), and both were superior to GALAD, PIVKA-II, AFP, and AFP-L3% (AUCs, 0.891, 0.869, 0.750, and 0.711) for discrimination of HCC from CLD for the entire dataset. The AUCs of the GALAD, GALAD-C and GAAP models were excellent for the hepatitis C virus (HCV) subgroup (0.939, 0.958 and 0.954), and for discrimination HCC from HCs (0.988, 0.982, and 0.979), but were relatively lower for the HBV subgroup (0.855, 0.904, and 0.894), and for HCC within Milan Criteria (0.810, 0.841, and 0.840). They were not superior to AFP (0.873) for discrimination of HCC from OMT (0.873, 0.809, and 0.823). GAAP achieved an AUC of 0.922 in the test dataset.Conclusion: GALAD was excellent for discrimination of HCC from CLD in the HCV subgroup of a cohort of Chinese patients. The GAAP and GALAD-C models achieved better performance compared with GALAD. These three models exhibited better performance in patients with an HCV etiology than those with HBV.Keywords: hepatocellular carcinoma, alpha-fetoprotein, PIVKA-II, GALAD

Fachen Zhou,1,2,* Jin Wang,2,* Xinming Chi,3 Xin Zhou,3 Zhou Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhou WangDepartment of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong Province 250021, People’s Republic of ChinaTel +86 53 168777893Email wangzhoushandong@163.comXin ZhouDepartment of Histology and Embryology, Dalian Medical University, No. 9 West Part of Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 41 186110314Email 18642818055@163.comPurpose: Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells.Materials and Methods: We screened differentially expressed lncRNAs between high- and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting.Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1.Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.Keywords: lung cancer, long non-coding RNA, TM4SF1-AS1, metastasis, PI3K/AKT signaling pathway

Xiaohui Chi, 1, 2,* Jing Guo, 1,* Yanzi Zhou, 1 Tingting Xiao, 1 Hao Xu, 1 Tao Lv, 1 Chunlei Chen, 1 Jian Chen, 3 Beiwen Zheng 1 1Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Environment and Health, School of Public Health, Shandong University, Jinan, People’s Republic of China; 3Intensive Care Unit, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this work.Correspondence: Beiwen Zheng; Jian Chen Tel/Fax +86-571-87236421; Tel +86-571-87236666Email zhengbw@zju.edu.cn; cjicu@zju.edu.cnBackground: Citrobacter freundii is the most common class of pathogens in the genus Citrobacter and is an important pathogen associated with certain underlying diseases or immune dysfunction. The aim of this study was to elucidate the resistance mechanism of clinically derived carbapenem-resistant C. freundii isolate and to characterize the genetic environment and delivery pattern of the IncN1 plasmid carrying the blaIMP-4 gene from C. freundii isolate.Materials and Methods: We identified a clinical isolate of C. freundii L91 carrying blaIMP-4 and performed phylogenetic analysis by whole-genome sequencing. The complete genomic sequence of L91 was obtained using the Illumina HiSeq 4000-PE150 and PacBio RS II platforms. Antimicrobial susceptibility testing was determined by the VITEK 2 system. Plasmid characteristics were presented by S1-pulsed-field gel electrophoresis (PFGE), Southern blotting and conjugation experiments.Results: S1-PFGE, Southern blot and conjugation assay confirmed the presence of blaIMP-4 genes on a conjugative plasmid in this isolate. C. freundii L91 and transconjugant L91-E. coli 600 strains both showed resistance to carbapenems. In silico analysis further showed that pIMP-4-L91 is an IncN1 plasmid with a length of 51,042 bp. Furthermore, blaIMP-4 gene was found encoded in the blaIMP-4-qacG2-aacA4-catB3 cassette array within a class 1 integron. A conserved structure sequence (ΔISKpn27-blaIMP-4-ΔISSen2-hp-hp-IS 6100) was found in the upstream and downstream of the blaIMP-4.Conclusion: We performed a comprehensive phylogenetic analysis of carbapenemase-resistant C. freundii and elucidated the resistance mechanism of clinically derived C. freundii L91. Not only that, we also found that the blaIMP-4 gene is located on the IncN1 plasmid and has a horizontal transfer function and a certain ability to spread. To lower the risk of the dissemination of such C. freundii isolates in clinical settings, more surveillance is needed in the future.Keywords: Citrobacter freundii, CPE, whole-genome sequencing, SNP, IncN, integron

Ruihong Wu,1 Dongfeng Geng,2 Xiumei Chi,1 Xiaomei Wang,1 Xiuzhu Gao,1 Hongqin Xu,1 Ying Shi,1 Yazhe Guan,1 Yang Wang,1 Jinglan Jin,1 Yanhua Ding,3 Junqi Niu1 1Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Centre for Reproductive Medicine, Centre for Prenatal Diagnosis, First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 3Phase I Clinical Research Center, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Yanhua DingPhase I Clinical Research Center, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 4 318 878 2168Email dingyanhua2003@126.comJunqi NiuDepartment of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 4 318 187 5101Email junqiniu@aliyun.comBackground and objective: Direct-acting antivirals (DAA) facing resistance continue to be used in some areas worldwide. Thus, identifying hepatitis C virus (HCV) genotypes/subtypes and loci with certain prevalent resistance-associated substitutions (RASs) deserves attention. We investigated the global and regional frequencies of naturally occurring RASs among all confirmed HCV subtypes (n=86) and explored co-occurring and mutually exclusive RAS pairs within and between genes NS3, NS5A, and NS5B.Methods: A total of 213,908 HCV sequences available as of July 10, 2019 were retrieved from the NCBI nucleotide database. After curation, 17,312 NS3, 8,478 NS5A, and 25,991 NS5B sequence fragments from DAA-naïve patients were screened for RASs. MEGA 6.0 was used to translate aligned nucleotide sequences into amino acid sequences, and RAS pairs were identified by hypergeometric analysis.Results: RAS prevalence varied significantly among HCV subtypes. For example, D168E, highly resistanct to all protease inhibitors except voxilaprevir, was nearly absent in all subtypes except in 43.48% of GT5a sequences. RASs in NS3 exhibiting significantly different global distribution included Q80K in GT1a with the highest frequency in North America (54.49%), followed by in Europe (22.66%), Asia (6.98%), Oceania (6.62%), and South America (1.03%). The prevalence of NS3 S122G in GT1b was highest in Asia (26.6%) and lowest in Europe (2.64%). NS5A L28M, R30Q, and Y93H in GT1b, L31M in GT2b, and NS5B C316N in GT1b was most prevalent in Asia. A150V in GT3a, associated with sofosbuvir treatment failure, was most prevalent in Asia (44.09%), followed by Europe (31.19%), Oceania (24.29%), and North America (19.05%). Multiple mutually exclusive or co-occurring RAS pairs were identified, including Q80K+R155K and R155K+D168G in GT1a and L159F+C316N and R30Q (NS5A)+C316N (NS5B) in GT1b.Conclusion: Our data may be of special relevance for those countries where highly effective antivirals might not be available. Considering the specific RASs prevalence will help the clinicians to make optimal treatment choices. The RASs pairs would benefit anti-HCV drug development.Keywords: hepatitis C virus, direct-acting antiviral, resistance-associated substitution, subtype

Xiaohui Chi,1,2,* Guangchun Hu,3,* Hao Xu,2 Xiucun Li,4 Tingting Xiao,2 Yanzi Zhou,2 Huiyu Xia,1 Huiyun Zou,1 Hui Han,4 Beiwen Zheng,2 Haiyan Gao,4 Xuewen Li1 1Department of Environment and Health, School of Public Health, Shandong University, Jinan 250012, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Division of Bacteria Diseases, Jinan Municipal Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Department of Infection Control, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuewen LiDepartment of Environment and Health, School of Public Health, Shandong University, Jinan 250012, People’s Republic of ChinaEmail lxw@sdu.edu.cnHaiyan GaoDepartment of Infection Control, Qilu Hospital of Shandong University, 107 Wenhua West Road, Jinan 250012, People’s Republic of ChinaEmail 565272040@qq.comPurpose: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteria causes nosocomial infections worldwide. However, KPC-producing K. pneumoniae outbreak has never been reported in Shandong Province, China. The purpose of our study was to elucidate the epidemiological and drug resistance mechanisms of KPC-producing K. pneumoniae strains collected from a large teaching hospital in Shandong during the outbreak. Moreover, we attempted to characterize the genetic environment and phylogenetic analysis of blaKPC-2 in outbreak isolates.Methods: We monitored a 64-day outbreak of infection in a general hospital in Shandong Province, and the bacteria causing the infection were all ST11-type K. pneumoniae. The genotype correlation of KPC-producing K. pneumoniae isolates was assessed by whole-genome sequencing (WGS) phylogenetic analysis. Subsequent studies included antibiotic susceptibility testing, multilocus sequence typing (MLST) and S1-pulsed-field gel electrophoresis (S1-PFGE), Southern blot hybridization.Results: From February 1, 2018 to April 5, 2018, 14 KPC-producing K. pneumoniae isolates from different wards were collected. All 14 isolates were resistant to carbapenems and carried the extended-spectrum β-lactamase (ESBL) gene as well as fosA, and sul genes. Whole-genome analysis showed that all 14 the outbreak isolates were all ST11 type. The blaKPC-2 carrying plasmids were all belong to IncFIIK2 type, and the size ranged from 94 kb to 368 kb.Conclusion: As far as we know, this report first describes the genomics characterization of KPC-2-producing K. pneumoniae outbreak isolates from Shandong Province, China. In our study, these isolates appeared to be cloned, and ST11 K. pneumoniae was the major clone caused the outbreak. Therefore, routine surveillance of such strains in this region is urgently warranted.Keywords: Klebsiella pneumoniae, ST11, whole-genome sequencing, SNP, outbreak, IncFIIK2

Xiaohui Chi, Man Li, Wei Mei, Mingfeng Liao Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Introduction: Acute pain is a common complication following cesarean section under general anesthesia. Post–cesarean section pain management is important for both the mother and the newborn. This study compared the effects of patient-controlled intravenous analgesia (PCIA) using sufentanil or tramadol on postoperative pain control and initiation time of lactation in patients who underwent cesarean section under general anesthesia.Methods: Primiparas (n=146) scheduled for cesarean section under general anesthesia were randomized to receive PCIA with sufentanil or tramadol. Movement-evoked and rest-pain intensity were assessed by the Numerical Rating Scale (NRS) postoperatively. The number of PCIA attempts, amount of drug consumed, initiation time of lactation, and Quality of Recovery Score 40 (QoR-40) were recorded at 4, 8, 12, and 24 h postoperatively. Pre- and postoperative serum prolactin levels were recorded.Results: No between-group difference existed in the NRS at rest at any time point postoperatively. Patients on sufentanil had more movement-evoked pain and a higher sedation score at 4, 8, and 12 h postoperatively, as compared with the tramadol group. At 24 h, the QoR-40 was higher in the tramadol group compared with the sufentanil group. No significant between-group differences were present in patient satisfaction and nausea/vomiting scores. Postpartum prolactin levels were significantly higher in the tramadol group versus the sufentanil group, corresponding with a significant delay in initiation of lactation in the latter.Conclusion: PCIA with tramadol may be preferred due to lower movement-evoked pain, higher quality of recovery, and earlier lactation in patients following cesarean section under general anesthesia. Keywords: sufentanil, tramadol, cesarean section, patient-controlled analgesia, prolactin

Trichophyton (T.) mentagrophytes is common tineas infection with high incidence in rabbits and also a classical zoonotic infection in people exposed to infected animals. However, many cases never got a correct diagnosis, let alone considerable management and treatment, which could cause certain economic losses in rabbit farms. An outbreak of a highly contagious skin disease infecting rabbits and accompanying all farm staff on a large scale rabbit farm in China was investigated. The disease was diagnosed by routine physical examinations, and the etiology of the disease was identified as T. mentagrophytes by fungal culture, sequence of ribosomal internal transcribed spacer (ITS+) and chitin synthase-1 gene (pchs-1). To date, there is no report of Dermatomycoses infection in rabbits accompanied by farm staff infection in mainland China. In this case, the etiology is identified by using advanced molecular techniques and clinical, microbiological aspects and the histological features of the infection are described.

Ruili Yu,1 Bo Yang,2 Xiaohua Chi,3 Lili Cai,4 Cui Liu,5 Lei Yang,6 Xueyan Wang,1 Peifeng He,7 Xuechun Lu2 1Department of Allergy, Beijing Shijitan Hospital, Affiliated to Capital Medical University, 2Department of Geriatric Hematology, Chinese PLA General Hospital, 3Department of Pharmacy, Chinese PLA Rocket Force General Hospital, 4Department of Geriatric Laboratory Medicine, 5Department of Geriatric Ultrasound, 6Medical Department, Nanlou Clinic, Chinese PLA General Hospital, Beijing, 7School of Medical Information Management, Shanxi Medical University, Taiyuan, People’s Republic of China Abstract: This study was designed to evaluate the efficacy and safety of cytokine-induced killer (CIK) cell-based immunotherapy as an adjuvant therapy for hepatocellular carcinoma (HCC). Published studies were identified by searching Medline, Cochrane, EMBASE, and Google Scholar databases with the keywords: cytokine-induced killer cell, hepatocellular carcinoma, and immunotherapy. The outcomes of interest were overall survival, progression-free survival, and disease-free survival. Eight randomized controlled trials (RCTs), six prospective studies, and three retrospective studies were included. The overall analysis revealed that patients in the CIK cell-treatment group had a higher survival rate (pooled hazard ratio (HR) =0.594, 95% confidence interval [CI] =0.501–0.703, P

Despite full immunoprophylaxis, mother-to-child transmission (MTCT) of Hepatitis B Virus still occurs in approximately 2-5% of HBsAg positive mothers. Little is known about the bottleneck of HBV transmission and the evolution of viral quasispecies in the context of MTCT. Here we adopted a newly developed tag linkage deep sequencing method and analyzed the quasispecies of four MTCT pairs that broke through immunoprophylaxis. By assigning unique tags to individual viral sequences, we accurately reconstructed HBV haplotypes in a region of 836 bp, which contains the major immune epitopes and drug resistance mutations. The detection limit of minor viral haplotypes reached 0.1% for individual patient sample. Dominance of "a determinant" polymorphisms were observed in two children, which pre-existed as minor quasispecies in maternal samples. In all four pairs of MTCT samples, we consistently observed a significant overlap of viral haplotypes shared between mother and child. We also demonstrate that the data can be potentially useful to estimate the bottleneck effect during HBV MTCT, which provides information to optimize treatment for reducing the frequency of MTCT.

Semiconductor compounds are widely used for photocatalytic hydrogen production applications, where photogenerated electron-hole pairs are exploited to induce catalysis. Recently, powders of a metallic oxide (Sr1-xNbO3, 0.033+δ and find that their bandgaps are ∼4.1 eV. Surprisingly, the carrier density of the conducting phase exceeds 1022 cm-3 and the carrier mobility is only 2.47 cm2 V-1 s-1. Contrary to earlier reports, the visible light absorption at 1.8 eV (∼688 nm) is due to the plasmon resonance, arising from the large carrier density. We propose that the hot electron and hole carriers excited via Landau damping (during the plasmon decay) are responsible for the photocatalytic property of this material under visible light irradiation.