Publications by authors named "Bing Ruan"

76 Publications

The role of fibrosis index FIB-4 in predicting liver fibrosis stage and clinical prognosis: A diagnostic or screening tool?

J Formos Med Assoc 2021 Jul 26. Epub 2021 Jul 26.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.
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http://dx.doi.org/10.1016/j.jfma.2021.07.013DOI Listing
July 2021

Indole-3-carbinol ameliorates necroptosis and inflammation of intestinal epithelial cells in mice with ulcerative colitis by activating aryl hydrocarbon receptor.

Exp Cell Res 2021 07 17;404(2):112638. Epub 2021 May 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang province, China. Electronic address:

Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1β, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.
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http://dx.doi.org/10.1016/j.yexcr.2021.112638DOI Listing
July 2021

Case Report: Next-Generation Sequencing in Diagnosis of Pneumonia Due to and Cytomegalovirus in a Patient With HIV Infection.

Front Med (Lausanne) 2021 29;8:653294. Epub 2021 Mar 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Pulmonary infections remain a significant cause of morbidity and mortality in immunocompromised patients. The pathogens spectrum of pulmonary infection that can affect patients with human immunodeficiency virus (HIV) is wide such as bacterial, fungal, viral, parasitic organisms, and so on. The risk of multi-pathogenic pneumonia is higher in HIV-infected patients. However, the fast and accurate diagnosis of multi-pathogenic pneumonia is challenging because of the limitations of current conventional tests. Here, we report a case of pneumonia due to and cytomegalovirus (CMV) in a 22-year-old male with newly diagnosed HIV infection. Blood tests revealed a low CD4 count, a chest computed tomography (CT) scan showed extensive ground-glass opacities in the bilateral lung with multiple cavity lesions in the left upper lung. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find any pathogens. There was also no evidence of pathogens known to cause pneumonia in bacteria and fungi culture tests and virus antibodies such as EBV, CMV, and COVID-19. The nucleic acid of CMV in blood was reported by quantitative PCR. Next-generation sequencing (NGS) analysis of BALF specimens identified a large number of and CMV reads, and confirmed the diagnosis of pneumonia due to and CMV. Following the patient's treatment with anti-PCP and anti-CMV, the patient was cured and discharged. This case highlights the combined application of NGS in the clinical diagnosis of multi-pathogenic pneumonia in an HIV-infected patient. NGS is proposed as an important adjunctive diagnostic approach for identifying pathogens of multi-pathogenic pneumonia in HIV-infected patients.
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http://dx.doi.org/10.3389/fmed.2021.653294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039302PMC
March 2021

Applicability of cutoff scores of Chinese Cumberland Ankle Instability Tool and Foot and Ankle Ability Measure as inclusion criteria for study of chronic ankle instability in Chinese individuals.

Phys Ther Sport 2021 Mar 28;48:116-120. Epub 2020 Dec 28.

School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China. Electronic address:

Objective: To examine the applicability of Chinese Cumberland Ankle Instability Tool (CAIT-C) and Foot and Ankle Ability Measure (FAAM-C) as inclusion criteria recommended by the International Ankle Consortium (IAC) for study of chronic ankle instability in the Chinese individuals.

Design: Cross-sectional comparative design with known groups.

Setting: Research laboratory.

Participants: 145 participants with chronic ankle instability (CAI) and 66 participants without injury.

Main Outcome Measures: CAIT-C and FAAM-C Activities of Daily Living (FAAM-C-ADL) and FAAM-C Sports (FAAM-C-Sports).

Results: The CAIT-C scores (18.2 ± 5.6), FAAM-C-ADL scores (97.0 ± 4.3) and FAAM-C-Sports scores (92.2 ± 10.3) of the CAI group were all lower than the CAIT-C scores (27.4 ± 3.1), FAAM-ADL scores (99.0 ± 2.1) and FAAM-Sports scores (98.4 ± 3.1) (P < 0.01) of the uninjured group. The recommended cutoff score of CAIT-C<24 by the IAC for identifying CAI had a sensitivity of 80.7% and a specificity of 84.9%. If the recommended cutoff scores of FAAM-ADL<90,FAAM-Sports<80 by the IAC as inclusion criteria for the study of CAI were applied, 97% of participants with CAI in this sample would be excluded.

Conclusion: The results support the recommended cutoff score of CAIT-C<24 by the IAC to identify Chinese individuals with CAI for study. However, the recommended cutoff scores of FAAM-ADL<90 and FAAM-Sports<80 will exclude most Chinese individuals with CAI having only mild functional impairments.
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http://dx.doi.org/10.1016/j.ptsp.2020.12.021DOI Listing
March 2021

Altered gut microbiota correlate with different immune responses to HAART in HIV-infected individuals.

BMC Microbiol 2021 01 6;21(1):11. Epub 2021 Jan 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79, QingChun Road, Hangzhou, 310003, China.

Background: Although gut microbiota dysbiosis has been reported in HIV infected individuals recently, the relationship between the gut microbiota and immune activation in patients with different immune responses to highly active antiretroviral therapy (HAART) is still not well understood. Gut microbiota and immune activation were studied in 36 non-HIV-infected subjects (healthy controls) and 58 HIV-infected individuals, including 28 immunological responders (IR) and 30 immunological non-responders (INR) (≥500 and < 200 CD4+ T-cell counts/μl after 2 years of HIV-1 viral suppression respectively) without comorbidities.

Results: Metagenome sequencing revealed that HIV-infected immunological responders and immunological non-responders could not recover completely from the gut microbiota dysbiosis. At a 97% similarity level, the relative abundances of Fusobacterium, Ruminococcus gnavus and Megamonas were greater, whereas Faecalibacterium, Alistipes, Bifidobacterium, Eubacterium rectale and Roseburia were more depleted in the IR and INR groups than those in the healthy controls. Ruminococcaceae and Alistipes were positively correlated with nadir and current CD4+ T-cell counts, but negatively correlated with CD8 + CD57+ T-cell counts. Inflammation markers and translocation biomarkers (LPS) levels were positively correlated with the abundances of genera Ruminococcus and Fusobacterium but were negatively correlated with the genus Faecalibacterium. The relative abundances of Escherichia-Shigella and Blautia were significantly higher in the IR than those in the INR group. Escherichia-Shigella were negatively correlated with the CD4/CD8 ratio but positively correlated with the amount of CD8 + CD57+ T-cells. Roseburia and Blautia were negatively associated with nadir CD4+ T-cell and positively associated with CD8 + CD57+ T-cell counts.

Conclusions: Gut microbiota dysbiosis may be one of the factors contributing to different immune responses and treatment outcomes to HAART.
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http://dx.doi.org/10.1186/s12866-020-02074-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789785PMC
January 2021

The Gender Difference in Association between Home-Based Environment and Different Physical Behaviors of Chinese Adolescents.

Int J Environ Res Public Health 2020 11 3;17(21). Epub 2020 Nov 3.

Department of Sports Science and Physical Education, Tsinghua University, Beijing 100084, China.

Purpose: The aim of this study was to evaluate the home-based physical activity (PA) environmental characteristics, and different types of physical behavior level of adolescents in different genders, and explore the impact of different domains of home-based PA environmental factors on different physical behaviors of adolescents in different genders.

Methods: Five hundred forty-four adolescents aged from 12 to 18 years old (males: = 358, females: = 186) and their parents were analyzed in this cross-sectional survey. The volume of various physical behaviors of all adolescent subjects were measured by the ActiGraph wGT3X-BT accelerometer, and the level in different domains of home-based environmental characteristics were assessed by the Gattshall's home-based PA environment questionnaire, which was answered by adolescents' parents. The difference in the volume of different physical behaviors was examined using Kruskal-Wallis analysis. The difference in home physical environment and home social environment for adolescents was examined using one-way analysis of variance (ANOVA). Multiple linear regression analysis in the adjusted model was used to evaluate the influence of different home-based PA environmental domains (PA availability, PA accessibility, Parental role-modeling of PA, and Parental policies around PA) on different physical behaviors (sedentary behavior, SB; light-intensity physical activity, LPA; and moderate-vigorous physical activity, MVPA) of adolescents (boys and girls).

Results: The volume of LPA and MVPA, the score of PA accessibility in the home physical environment, and the score of home social environment of boys are significantly higher than those of girls, while the SB volume of boys is significantly lower than that of girls. The PA availability, the parents' role-modeling of PA in same-sex parent-child dyads, and the parents' policies around PA in opposite-sex parent-child dyads are significantly associated with adolescents' decreased SB and increased LPA and MVPA.

Conclusion: There is significant gender difference in adolescents' physical behaviors and home-based environmental characteristics, as well as in the association between adolescents' physical behaviors and their home-based environment. The PA availability, the parents' role-modeling of PA in same-sex parent-child dyads, and the parents' policies around PA in opposite-sex parent-child dyads can significantly promote adolescents' healthy physical behaviors.
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http://dx.doi.org/10.3390/ijerph17218120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663369PMC
November 2020

Both Gut Microbiota and Differentially Expressed Proteins Are Relevant to the Development of Obesity.

Biomed Res Int 2020 24;2020:5376108. Epub 2020 Sep 24.

The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.
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http://dx.doi.org/10.1155/2020/5376108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533028PMC
April 2021

Safety reassessment of cinobufotalin injection: new findings into cardiotoxicity.

Toxicol Res (Camb) 2020 Jul 12;9(4):390-398. Epub 2020 Jun 12.

China State Institutes of Pharmaceutical Industry National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai, China.

Cinobufotalin injection, a traditional Chinese medicine preparation, successfully used for several years, might induce cardiotoxicity. The aim of the study was to evaluate the cardiotoxicity of cinobufotalin injection and the cardiotoxicity-preventive effect of sodium phenytoin . According to the 4 × 4 Latin square design, four Beagle dogs were allocated into four dose levels of 0, 0.3, 1, and 3 g/kg in treatment phases I-IV (cinobufotalin injection) and 3 g/kg in treatment phase V (cardiotoxicity antidote). The following parameters and endpoints were assessed: clinical observations, body weight, indicators of myocardial injury, and electrocardiogram (ECG) parameters. The cinobufotalin injection-related changes were observed in clinical observations (rapid breathing pattern), indicators of myocardial injury (increased cardiac troponin I, creatine kinase isoenzymes, and aspartate aminotransferase), and ECG graphics (arrhythmia) at 3 g/kg concentration in treatment phases I-IV. The cardiotoxicity of cinobufotalin injection was attenuated by sodium phenytoin in treatment phase V. The results confirmed the cardiotoxicity of cinobufotalin injection, and they might bring information about the appropriate monitoring time points and cardiotoxicity parameters in clinical practices and shed light on the treatment of cardiovascular adverse reactions.
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http://dx.doi.org/10.1093/toxres/tfaa035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467235PMC
July 2020

Altered gut bacterial-fungal interkingdom networks in patients with current depressive episode.

Brain Behav 2020 08 12;10(8):e01677. Epub 2020 Jun 12.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Introduction: Bacterial dysbiosis has been described in patients with current depressive episode (CDE); however, the fungal composition in the gut has not been investigated in these patients.

Methods: Here, we characterized the fungal gut mycobiota in patients with CDE. We systematically characterized the microbiota and mycobiota in fecal samples obtained from 24 patients with CDE and 16 healthy controls (HC) using 16S rRNA gene- and ITS1-based DNA sequencing, respectively.

Results: In patients with CDE, bacterial dysbiosis was characterized by an altered composition and reduced correlation network density, and the gut mycobiota was characterized by a relative reduction in alpha diversity and altered composition. Most notably, the CDE group had higher levels of Candida and lower level of Penicillium than the HC group. Compared with the HC group, the gut microbiota in patients with CDE displayed a significant disruption in the bacteria-fungi correlation network suggestive of altered interkingdom interactions. Furthermore, a gut microbial index based on the combination of eight genera (four bacterial and four fungal CDE-associated genera) distinguished CDE patients from controls with an area under the curve of approximately 0.84, suggesting that the gut microbiome signature is a promising tool for disease classification.

Conclusions: Our findings suggest that both bacteria and fungi contribute to gut dysbiosis in patients with CDE. Future studies involving larger cohorts and metagenomic or metabolomic analyses may clarify the structure and potential roles and functions of the gut mycobiome and its impact on the development of CDE.
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http://dx.doi.org/10.1002/brb3.1677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428472PMC
August 2020

Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19).

Clin Infect Dis 2020 07;71(15):799-806

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou City, China.

Background: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding.

Methods: In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan.

Results: The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13-22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31-8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10-1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11-88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding.

Conclusions: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.
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http://dx.doi.org/10.1093/cid/ciaa351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184421PMC
July 2020

Analysis of gut mycobiota in first-episode, drug-naïve Chinese patients with schizophrenia: A pilot study.

Behav Brain Res 2020 02 20;379:112374. Epub 2019 Nov 20.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Background: Accumulating evidence has focused on elucidating the bacterial component of the gut microbiota in patients with schizophrenia (SC); however, the fungal composition in the gut has not been investigated, although previous studies have suggested that gut mycobiota may be intricately linked to this disorder. The purpose of this analysis was to examine gut bacterial and fungi in first-episode, drug- naïve adult SC patients in relation to age- and sex-matched healthy controls (HC).

Methods: Ten SC patients and 16 HCs were enrolled in this cross-sectional study, and their gut microbiota and mycobiota were systematically characterized using 16S rRNA gene- and ITS1-based DNA sequencing.

Results: The microbiota of the SC patients were characterized by increased abundance of harmful bacterial (Proteobacteria) and decreased short-chain fatty acid (SCFA)-producing bacteria, such as the Faecalibacterium and Lachnospiraceae genera. The gut mycobiota were characterized by a relative reduction in alpha diversity and altered composition. Most notably, the SC group had a higher level of Chaetomium and a lower level of Trichoderma than the HC group. Furthermore, the gut microbiota in patients with SC displayed a significant enhancement in the bacteria-fungi correlation network, suggestive of altered interkingdom interactions.

Conclusions: Both the bacterial gut microbiota as well as the gut mycobiota contributed to gut dysbiosis in patients with SC. However, our study was limited by sample size, and additional studies involving larger cohorts characterizing the gut mycobiome in SC patients are needed to form a foundation for research into the relationship between mycobiota, dysbiosis, and SC development.
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http://dx.doi.org/10.1016/j.bbr.2019.112374DOI Listing
February 2020

Both gut microbiota and cytokines act to atherosclerosis in ApoE-/- mice.

Microb Pathog 2020 Jan 1;138:103827. Epub 2019 Nov 1.

The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously.

Methods: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis.

Results: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified.

Conclusions: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.
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http://dx.doi.org/10.1016/j.micpath.2019.103827DOI Listing
January 2020

Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China.

BMC Infect Dis 2019 Jul 12;19(1):617. Epub 2019 Jul 12.

Xinjiang Provincial Center for Disease Control and Prevention, Urumchi, China.

Background: The major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control.

Methods: Based on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents' epidemiological data. In addition, a special quality control team was set up for CCI project.

Results: After two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing.

Conclusions: CCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable.

Trial Registration: The project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled "The prevention and control of AIDS, viral hepatitis and other major infectious diseases", Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.
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http://dx.doi.org/10.1186/s12879-019-4150-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626343PMC
July 2019

Human papillomavirus vaccination and the risk of autoimmune disorders: A systematic review and meta-analysis.

Vaccine 2019 05 26;37(23):3031-3039. Epub 2019 Apr 26.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. Electronic address:

Introduction: Human papillomavirus (HPV) vaccination has been proven to effectively protect against HPV infection and infection-associated cancer. However, there are concerns about the relationship between HPV vaccination and the risk of autoimmune disorders (ADs). Therefore, we performed a systematic review and meta-analysis to comprehensively evaluate the relationship between HPV vaccination and ADs risk.

Methods: To identify relevant studies, we conducted a systematic search in EMBASE and PubMed databases of scientific articles published through June 2018. Fixed or random effects models were adopted to estimate overall relative risk.

Results: In total, 20 studies (12 cohort studies, 6 case-control studies, and 2 randomized controlled trials) involving more than 169,000 AD events were included in our meta-analysis. Our results show that HPV vaccination was not associated with an increased risk of subsequent ADs (odds ratio [OR] = 1.003, 95% confidence interval (CI): 0.95-1.06), particularly among those with a prior ADs (OR = 0.82, 95% CI: 0.7-0.96). Most of the subgroup analysis results based on the location or type of ADs were consistent with the overall results.

Conclusion: No evidence of an association between HPV vaccination and ADs was found. Given the low number of estimates for individual AD, additional and larger observational studies are needed to verify our findings.
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http://dx.doi.org/10.1016/j.vaccine.2019.04.049DOI Listing
May 2019

A system dynamics modelling simulation based on a cohort of hepatitis B epidemic research in east China community.

Epidemiol Infect 2019 02 28;147:e86. Epub 2019 Feb 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Hepatitis B constitutes a severe public health challenge in China. The Community-based Collaborative Innovation hepatitis B (CCI-HBV) project is a national epidemiological study of hepatitis B and has been conducting a comprehensive intervention in southern Zhejiang since 2009.The comprehensive intervention in CCI-HBV areas includes the dynamic hepatitis B screening in local residents, the normalised treatment for hepatitis B infections and the upcoming full-aged hepatitis B vaccination. After two rounds of screening (each round taking for 4 years), the initial epidemiological baseline of hepatitis B in Qinggang was obtained, a coastal community in east China. By combining key data and system dynamics modelling, the regional hepatitis B epidemic in 20 years was predicted.There were 1041 HBsAg positive cases out of 12 228 people in Round 1 indicating HBV prevalence of 8.5%. Of the 13 146 people tested in Round 2, 1171 people were HBsAg positive, with a prevalence of 8.9%. By comparing the two rounds of screening, the HBV incidence rate of 0.192 per 100 person-years was observed. By consulting electronic medical records, the HBV onset rate of 0.533 per 100 person-years was obtained. We generated a simulated model to replicate the real-world situation for the next two decades. To evaluate the effect of interventions on regional HBV prevalence, three comparative experiments were conducted.In this study, the regional hepatitis B epidemic in 20 years was predicted and compared with HBV prevalence under different interventions. Owing to the existing challenges in research methodology, this study combined HBV field research and simulation to provide a system dynamics model with close-to-real key data to improve prediction accuracy. The simulation also provided a prompt guidance for the field implementation.
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http://dx.doi.org/10.1017/S0950268819000220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518579PMC
February 2019

An fluorescent aptasensor for sensitive detection of tumor marker based on the FRET of a sandwich structured QDs-AFP-AuNPs.

Talanta 2019 May 3;197:444-450. Epub 2019 Jan 3.

State Key Laboratory for Diagnosis and Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

The detection of alpha-fetoprotein (AFP) is of great importance for hepatocellular carcinoma (HCC) diagnosis, but it needs to be further improved because of poor sensitivity and complicated operating steps. In this paper, a simple and sensitive homogeneous apatasensor for AFP has been developed based on Förster resonance energy transfer (FRET) where the AFP aptamer labeled luminescent CdTe quantum dots (QDs) as a donor and anti-AFP antibody functional gold nanoparticles (AuNPs) as an acceptor. In the presence of AFP, the bio-affinity between aptamer, target, and antibody made the QDs and AuNPs close enough, thus the fluorescence of CdTe QDs quenched though the FRET between QD and AuNP. The fluorescent aptasensor for AFP showed a concentration-dependent decrease of fluorescence intensity in the low nanomolar range and a detecting linear range of 0.5-45 ng mL, with a detection limit of 400 pg mL. Moreover, this homogeneous aptasensor is simple and reliable, and obtained satisfying results for the detection of AFP in human serum samples. With more and more aptamers for biomarkers have been selected gradually, this approach could be easily extended to detection of a wide range of biomarkers. The proposed aptasensor has great potential for carcinoma screening in point-of-care testing and even in field use.
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http://dx.doi.org/10.1016/j.talanta.2019.01.012DOI Listing
May 2019

The Burden of Chronic Hepatitis C in China From 2004 to 2050: An Individual-Based Modeling Study.

Hepatology 2019 04 18;69(4):1442-1452. Epub 2019 Mar 18.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

The launch of new direct-acting antivirals (DAAs) is expected to substantially reduce the burden of hepatitis C virus (HCV) in China. However, the effect of these changes has not yet been modeled in China. Therefore, we aim to predict the burden of HCV-related diseases in China by simulating different scenarios that incorporate recent therapeutic advances of HCV and China's current screening strategy. We developed an individual-based microsimulation Markov model that simulated disease progression of HCV-infected patients in China from 2004 to 2050. We simulated four scenarios with different assumptions about treatment, including a natural history scenario, a pre-DAAs scenario, a DAA treatment for all patients with a METAVIR fibrosis score ≥F3 (DAAs [≥F3]) scenario, and a DAAs (≥F0) scenario. The introduction of DAAs is predicted to have great impacts on the burden of HCV in China, particularly under the DAAs (≥F0) scenario in which we rapidly expand DAAs to all HCV-infected patients (≥F0) in 2021. Under this scenario, prevalence of chronic HCV is expected to peak at 10.75 million (95% confidence interval [CI], 8.30-12.85) around 2020 and then decrease to 7.92 million (95% CI, 5.41-10.08) in 2050. Conclusion: If the future increasing burden of HCV-related diseases is to be averted, China needs to start launching the new DAA treatment and rapidly increase the number of patients treated. However, to maximize the benefits of new DAAs, expanded screening is necessary to identify more cases that require treatment in the short term. Without these changes, the HCV burden in China will remain high in the future.
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http://dx.doi.org/10.1002/hep.30476DOI Listing
April 2019

The microbiome in bipolar depression: A longitudinal study of one pair of monozygotic twins.

Bipolar Disord 2019 02 3;21(1):93-97. Epub 2019 Feb 3.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.1111/bdi.12736DOI Listing
February 2019

Suitable hepatitis B vaccine for adult immunization in China: a systematic review and meta-analysis.

Hum Vaccin Immunother 2019 5;15(1):220-227. Epub 2018 Sep 5.

b The Office of the National Science and Technology Project , Zhejiang Provincial Centers for Disease Control and Prevention , Hangzhou , Zhejiang , China.

Hepatitis B virus (HBV) infection remains an important public health problem in China, and adults need to be vaccinated. This systematic review and meta-analysis assessed the appropriate immunization of adults in China. Only randomized controlled trials (RCTs) were eligible, and seroprotection was defined as anti-HBs≥ 10 mIU/ml; 18,308 participants in 27 studies were included. Relative risk (RR) and random effects models were used. Twenty micrograms of HBV vaccine resulted in a better response than 10 μg (RR: 1.05, 95% confidence interval (CI): 1.02 to 1.08), and the 0-, 1-, and 6-month schedule was more effective than the 0-, 1-, and 2 - or 3-month schedule (RR: 0.98, 95% CI: 0.96 to 1.00). No significant differences were observed between 10 μg and 5 μg (RR: 1.05, 95% CI: 0.88 to 1.01); (yeast-derived hepatitis B vaccines) YDV and recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine (RR: 1.01, 95% CI: 0.98 to 1.04); domestic and imported (RR: 1.02, 95% CI: 0.99 to 1.05); or 0-, 1-, and 6-month and 0-, 1-, and 12-month schedules (RR: 1.02, 95% CI: 0.89 to 1.08). In conclusion, 20 μg of vaccine is recommended for adults in China, and the 0-, 1-, and 12-month immunization program schedule is also worth choosing when it is not possible to complete the 0-, 1-, and 6-month schedule.
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http://dx.doi.org/10.1080/21645515.2018.1509172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363055PMC
February 2020

Altered gut microbiota profile in patients with generalized anxiety disorder.

J Psychiatr Res 2018 09 18;104:130-136. Epub 2018 Jul 18.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address:

Close relationships have recently been established between gut microbiota and some mental disorders. Here, we performed a systematic comparative analysis of the gut microbiome in patients with generalized anxiety disorder (GAD) and healthy controls (HCs). We first conducted a cross-sectional study of 40 patients with GAD in the active state and 36 HCs. Second, subgroup analysis consisting of 12 antidepressant-naive patients and 22 controls was performed to validate the results. Finally, a prospective study was performed in a subgroup of nine patients with GAD who underwent analysis in the active state of anxiety and in remission. Compared with the HCs, we found markedly decreased microbial richness and diversity, distinct metagenomic composition with reduced short-chain fatty acid (SCFA)-producing bacteria (associated with a healthy status) and overgrowth of bacteria, such as Escherichia-Shigella, Fusobacterium and Ruminococcus gnavus. Unexpectedly, these changes in the genera were not reversed in remissive GAD. This study identified microbiota dysbiosis of gut microbiota in GAD patients, suggesting that targeting the microbiome may be a useful therapeutic and preventive target for GAD.
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http://dx.doi.org/10.1016/j.jpsychires.2018.07.007DOI Listing
September 2018

Gut microbiota profiles in treatment-naïve children with attention deficit hyperactivity disorder.

Behav Brain Res 2018 07 23;347:408-413. Epub 2018 Mar 23.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China. Electronic address:

Backgrounds: Although increasing evidence suggests a role for the gut microbiota in neurodevelopment, the actual structure and composition of microbiota in children with attention-deficit/hyperactivity disorder (ADHD) remain unclear.

Methods: Thus, the present study aimed to define the characteristics of gut microbiota in treatment-naive children with ADHD and to assess their relationship with the severity of ADHD symptoms. High-throughput pyrosequencing was used to investigate the microbiota composition in fecal matter from 51 children with ADHD and 32 healthy controls (HC).

Results: An operational taxonomical unit (OTU)-level analysis revealed a significant decrease in the fractional representation of Faecalibacterium in children with ADHD compared to HC. In individuals with ADHD, the abundance of Faecalibacterium was negatively associated with parental reports of ADHD symptoms. However, there was no significant difference in alpha diversity between the ADHD and control groups.

Conclusions: This present findings support the involvement of microbiota alteration in psychiatric diseases and Faecalibacterium may represent a potential novel marker of gut microbiota in ADHD. Future studies are needed to validate these findings and to elucidate the temporal and causal relationships between these variables.
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http://dx.doi.org/10.1016/j.bbr.2018.03.036DOI Listing
July 2018

The effects of booster vaccination of hepatitis B vaccine on children 5-15 years after primary immunization: A 5-year follow-up study.

Hum Vaccin Immunother 2018 05 26;14(5):1251-1256. Epub 2018 Feb 26.

b The National Science and Technology Project , Zhejiang Provincial Center for Disease Control and Prevention , Hangzhou , Zhejiang , China.

The aim of this study was to evaluate changes in hepatitis B surface antibody titers (anti-HBs) after booster vaccinations in children aged 5-15 y and to provide suitable immunization strategies. A total of 2208 children were initially enrolled in screening, and 559 children were finally included. The participants were divided into 2 groups according to their pre-booster anti-HBs levels: Group I, <10 mIU/ml and Group II, ≥10 mIU/ml. Group I was administered 3 doses of booster hepatitis B vaccine (0-1-6 months, 10 μg), and Group II was administered 1 dose of booster hepatitis B vaccine (10 μg). The antibody titer changes were examined at 4 time points: 1 month after dose 1 and dose 3, and 1 year and 5 years after dose 3. The protective seroconversion rates at those points were 95.65%, 99.67%, 97.59% and 91.05% (p < 0.001), respectively, in Group I, and 100.00%, 99.87%, 99.66% and 98.21% (χ = 6.04, p = 0.11), respectively, in Group II. The GMT in subjects aged 5-9 y were higher than that in subjects aged 10-15 y in both Group I and Group II at 1 month after dose 1, but no difference was observed at the other three time points. This study demonstrates that booster vaccination has a good medium-term effect. A booster dose for subjects with protective antibodies is not necessary but effective, and 3 doses of hepatitis B vaccination are recommended for those who have lost immunological memory. Receiving booster immunization at the age of 10-15 years may be more appropriate for individuals living in HBV high epidemic areas.
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http://dx.doi.org/10.1080/21645515.2018.1426419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989910PMC
May 2018

Hepatitis B virus infection in hilly/mountainous regions of southeastern China: a locality-dependent epidemiology.

BMC Infect Dis 2017 12 29;17(1):809. Epub 2017 Dec 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing-Chun Road, Hangzhou, 310003, China.

Background: The overall prevalence of hepatitis B virus (HBV) infection in China is declining. The purpose of this study was to use a community-based epidemiological study to update the infection status of hepatitis B virus (HBV) in mountainous regions of China, and to evaluate the impact of the Expanded Program of Immunization (EPI) on HBV transmission.

Methods: In total, 10,383 participants were selected by multi-stage stratified random cluster sampling in two mountainous regions, Xianju and Anji, in Zhejiang province, China.

Results: The positive rates of hepatitis B virus surface antigen (HBsAg), anti-HBV core antigen (anti-HBc), and anti-HBV surface antigen (anti-HBs) were 9.5%, 33.9%, and 51.0%, respectively. Positive HBV markers were more frequently detected in males than in females (P < 0.01). The alanine aminotransferase (ALT) levels were elevated (>38 IU/L) in 15.3% of the HBsAg-positive and 6.3% of the HBsAg-negative subjects. The α-fetoprotein (AFP) level was elevated in 0.8% of the HBsAg-positive participants who were older than 30 years old.

Conclusions: The epidemiology of HBV infection is location dependent. The prevalence of HBV infection in the mountainous regions is higher than the national levels. Moreover, HBV infection in women of childbearing age is up to 10%, which represents a main factor for continuous HBV transmission.
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http://dx.doi.org/10.1186/s12879-017-2922-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747104PMC
December 2017

Serum insulin-like growth factor-1 and its binding protein 3 as prognostic factors for the incidence, progression, and outcome of hepatocellular carcinoma: a systematic review and meta-analysis.

Oncotarget 2017 Oct 12;8(46):81098-81108. Epub 2017 Jul 12.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Purpose: Previous studies have supported an association between serum insulin-like growth factor-1 (IGF1) and IGF-binding protein 3 (IGFBP3) levels and hepatocellular carcinoma (HCC), but the results were inaccurate. It has recently been proposed that IGF1 and IGFBP3 play roles in the time-to-progression (TTP) and overall survival (OS) of HCC patients. Our results revealed that serum IGF1 level is predictive of the progression and survival of HCC patients.

Results: HCC was associated with a significant reduction in serum IGF-1 and IGFBP-3 levels compared to cirrhosis ( = 0.037). Low serum IGF1 levels were predictive of a shorter TTP (OR, 2.74; 95% confidence interval [CI], 1.92-3.90) and poorer OS (odds ratio [OR], 2.20; 95% CI, 1.81-2.68) in HCC patients. The IGF1/IGFBP3 molar ratio was not significantly associated with the risk of HCC (OR, 1.311; 95% CI, 0.761-2.260).

Materials And Methods: We conducted a comprehensive literature search in PubMed, EMBASE, and the Cochrane Library. Twenty studies met the inclusion criteria and were subjected to statistical analysis. The geometric mean and standard deviation (SD) of serum IGF1 and IGFBP3 levels in the healthy, cirrhosis, and HCC groups were calculated. Pooled odds ratios (ORs) were calculated using a fixed-effects model to analyse the association of serum IGF1 level with the progression and survival of HCC patients.

Conclusions: Serum IGF1 and IGFBP3 levels were positively associated with the incidence of HCC. Serum IGF1 level is an independent prognostic factor for the progression and survival of HCC patients.
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http://dx.doi.org/10.18632/oncotarget.19186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655265PMC
October 2017

Pneumonia Mortality in Children Aged <5 Years in 56 Countries: A Retrospective Analysis of Trends from 1960 to 2012.

Clin Infect Dis 2017 Oct;65(10):1721-1728

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University.

Background: Pneumonia is now the second leading cause of death for children aged <5 years worldwide. However, analyses of the long-term evolution of under-5 mortality from pneumonia are still scarce in the literature. We aimed to explore long-term trends of under-5 mortality from pneumonia in 56 countries from 1960 to 2012.

Methods: Data on under-5 mortality from pneumonia were extracted from the World Health Organization mortality database. Long-term trends were assessed for 56 countries and for 4 national income transition groups. We also used joinpoint regression analysis to detect distinct period segments of long-term trends and estimate the annual percent of changes of each period segment.

Results: The average mortality rate from pneumonia for children aged 0-4 years in 56 countries declined from 163.0 per 100000 children (95% confidence interval [CI], 119.4 to 212.8) in 1960 to 9.9 per 100000 children (95% CI, 6.4 to 13.4) in 2012, with an average annual percent of change of -5.6% (95% CI, -7.2% to -3.9%). The temporal trends of childhood mortality were different between national income transition groups.

Conclusions: Our findings suggest a striking overall downward trend in under-5 mortality from pneumonia between 1960 and 2012. However, the rate and absolute terms of decline differ by national income transition group. These variable patterns between national income transition groups may inform further intervention setting and priority setting.
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http://dx.doi.org/10.1093/cid/cix633DOI Listing
October 2017

Serum HBeAg and HBV DNA levels are not always proportional and only high levels of HBeAg most likely correlate with high levels of HBV DNA: A community-based study.

Medicine (Baltimore) 2017 Aug;96(33):e7766

Shulan Hospital, Zhejiang University International Hospital, Hangzhou State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

This study aimed to investigate the correlation between quantitative hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels, and to determine whether semiquantitative measurement of HBeAg can indicate the extent of HBV replication in HBeAg-positive subjects in the immune tolerant phase.A cross-sectional, community-based survey was carried out in 12 communities of 2 counties in Zhejiang Province, China. A panel of 788 HBeAg-positive subjects was divided into 4 groups according to HBV DNA level.Groups I (n = 111), II (n = 91), III (n = 124), and IV (n = 462) had HBV DNA levels below 10 copies/mL (PCR undetectable), between 10 and 10 copies/mL (PCR detectable), between 10 and 2 × 10 copies/mL (hybridization detectable), and >2 × 10 copies/mL, respectively. The HBeAg level correlated well with the HBV DNA level (R = 0.658; P < .01) on a log scale. The average HBeAg level in group IV was significantly higher than those in the other 3 groups, and the best HBeAg cut-off value for differentiating group IV from the other 3 groups was 768 S/CO, with a sensitivity of 94.4% and specificity of 91.1%.Semiquantification of HBeAg could indicate a relative HBV DNA level in HBeAg-positive subjects in the immune tolerant phase.
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http://dx.doi.org/10.1097/MD.0000000000007766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571692PMC
August 2017

Tuberculosis in China: A longitudinal predictive model of the general population and recommendations for achieving WHO goals.

Respirology 2017 10 28;22(7):1423-1429. Epub 2017 May 28.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background And Objective: Tuberculosis (TB) remains a major public health challenge. China accounts for more than 10% of the global TB burden, and effective modelling of TB trends remains limited.

Methods: We used data drawn primarily from two Chinese nation-wide cross-sectional epidemiological surveys combined with data from China's National Disease Reporting Network to construct an eight-state Markov model that simulates TB prevalence. By adjusting the relevant parameters, we evaluated which characteristics have the greatest bearing upon prevalence and efficacy of the response measures.

Results: If current trends continue, the prevalence of TB in China will enter an 8-year period of decline from approximately 390 to 200 cases per 100 000 population and stabilize at 163 cases per 100 000 population, which is a figure well above the World Health Organization (WHO) goal of eliminating TB by 2050. We find that the proportion of notified cases in the population, the rate of progression from latent to active and the overall treatment success rate are the chief factors affecting disease progression.

Conclusion: We suggest a 90-90-90 strategy, wherein the proportion of notified cases in the population reaches 90%, the risk of progression from latent to active is decreased by 90% compared with the current level and the overall treatment success rate is increased to 90%. This strategy could reduce TB prevalence to less than 10 cases per 100 000 population within 5 years and to 1.77 cases per 100 000 population within 50 years.
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http://dx.doi.org/10.1111/resp.13078DOI Listing
October 2017

Clinical features of treatment-naive patients with hepatitis B virus infection: A community-based survey from high- and intermediate-hepatitis B endemicity regions in Southeast China.

Medicine (Baltimore) 2017 Apr;96(16):e6660

aState Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University bCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.

The aim of study was to investigate the clinical features of treatment-naive patients in 2 regions with high- and intermediate-hepatitis B endemicity level in Southeast China and provide the baseline data for monitoring health or planning therapy.This study included 8207 cases of treatment-naive patients with hepatitis B virus (HBV) infection from Yuhuan (YH, high-hepatitis B endemicity region) and Shaoxing (SX, intermediate-hepatitis B endemicity region) during 2014-2015. Clinical data were collected from the patients. Blood samples were kept for detecting hepatitis B surface antigen, hepatitis B envelope antigen (HBeAg), hepatitis B envelope antibody, hepatitis B surface antibody, hepatitis B core antibody, liver function, HBV deoxyribonucleic acid, and alpha-fetoprotein. All persons underwent B ultrasound to exclude liver cirrhosis or cancer.Of all 8207 HBsAg-positive patients, 52.9% patients were in the low-replication (LR) stage and 30.3% in the HBeAg-negative chronic hepatitis B (ENH) stage; 8.8% cases were in the ENH stage with elevated alanine aminotransferase (ALT). More male than female patients were in immune clearance (IC) or ENH stages with elevated ALT (10.4% vs 4.8%, 12.1% vs 5.3%, respectively, P < .05). The percentage of patients in IC and immune tolerant (IT) stages declined with increasing age, whereas the percentages of ENH with elevated ALT stage were highest in 40 to 60 years.The percentage of patients in IT and IC stages was higher in YH than in SX (9.4% vs 3.8%, 9.9% vs 4.2%, respectively, P < .05). More patients had HBVDNA≥10 IU/mL in YH than in SX (24.6% vs 16.0%, P < .05), and more male than female patients had HBVDNA≥10 IU/mL(24.5% vs 17.9%, P < .05).Clinical features varied in treatment-naive patients with HBV infection between different genders and regions. More attention should be paid to the surveillance and therapy of patients in YH especially male patients for the prevention and prognosis of hepatitis B.
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http://dx.doi.org/10.1097/MD.0000000000006660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406089PMC
April 2017

Epidemiological features of and changes in incidence of infectious diseases in China in the first decade after the SARS outbreak: an observational trend study.

Lancet Infect Dis 2017 07 12;17(7):716-725. Epub 2017 Apr 12.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: The model of infectious disease prevention and control changed significantly in China after the outbreak in 2003 of severe acute respiratory syndrome (SARS), but trends and epidemiological features of infectious diseases are rarely studied. In this study, we aimed to assess specific incidence and mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China and to investigate the overall effectiveness of current prevention and control strategies.

Methods: Incidence and mortality data for 45 notifiable infectious diseases were extracted from a WChinese public health science data centre from 2004 to 2013, which covers 31 provinces in mainland China. We estimated the annual percentage change in incidence of each infectious disease using joinpoint regression.

Findings: Between January, 2004, and December, 2013, 54 984 661 cases of 45 infectious diseases were reported (average yearly incidence 417·98 per 100 000). The infectious diseases with the highest yearly incidence were hand, foot, and mouth disease (114·48 per 100 000), hepatitis B (81·57 per 100 000), and tuberculosis (80·33 per 100 000). 132 681 deaths were reported among the 54 984 661 cases (average yearly mortality 1·01 deaths per 100 000; average case fatality 2·4 per 1000). Overall yearly incidence of infectious disease was higher among males than females and was highest among children younger than 10 years. Overall yearly mortality was higher among males than females older than 20 years and highest among individuals older than 80 years. Average yearly incidence rose from 300·54 per 100 000 in 2004 to 483·63 per 100 000 in 2013 (annual percentage change 5·9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed the fastest growth. The overall increasing trend changed after 2009, and the annual percentage change in incidence of infectious disease in 2009-13 (2·3%) was significantly lower than in 2004-08 (6·2%).

Interpretation: Although the overall incidence of infectious diseases was increasing from 2004, the rate levelled off after 2009. Effective prevention and control strategies are needed for diseases with the highest incidence-including hand, foot, and mouth disease, hepatitis B, and tuberculosis-and those with the fastest rates of increase (including hydatid disease, hepatitis C, and syphilis).

Funding: Chinese Ministry of Science and Technology, National Natural Science Foundation (China).
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http://dx.doi.org/10.1016/S1473-3099(17)30227-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164789PMC
July 2017

Immune response to hepatitis B vaccination among people with inflammatory bowel diseases: A systematic review and meta-analysis.

Vaccine 2017 05 9;35(20):2633-2641. Epub 2017 Apr 9.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Hangzhou, Zhejiang 310003, China. Electronic address:

Introduction: The response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low and varies markedly. We performed a systematic review and meta-analysis to determine the response rate to HBV vaccination and identified the factors predictive of an immune response.

Methods: We searched PubMed, Cochrane Library, and Embase databases, and reviewed the titles and abstracts of studies on the efficacy of HBV vaccination in IBD patients performed through July 2016. Anti-HBs levels>10IU/L was considered to be an effective immune response. The primary outcome measure was the response rate to HBV vaccination after series completion, and the secondary outcome was identification of factors at baseline predictive of an immune response.

Results: Thirteen studies including 1688 patients were eligible for inclusion. Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53-69). Young age (mean difference [MD]: -5.7; 95% CI: -8.46, -2.95) and vaccination during disease remission (relative risk [RR]: 1.62; 95% CI: 1.15-2.29) were associated with a positive response to HBV vaccination. In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95% CI: 1.08-1.63) or anti-tumor necrosis factor-α (anti-TNF-α) (RR: 1.57; 95% CI: 1.19-2.08) therapy.

Conclusions: Based on this meta-analysis, only three of five IBD patients will show a serological response to HBV vaccination. Vaccination should be performed at the time of IBD diagnosis, during disease remission, or before starting immunosuppressive therapy.
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http://dx.doi.org/10.1016/j.vaccine.2017.03.080DOI Listing
May 2017
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