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

Characterization of HIV-1 subtypes and transmitted drug resistance among treatment-naive HIV-infected individuals in Zhejiang, China, 2014-2017.

In recent years, transmitted drug resistance (TDR) has adversely impacted upon first-line therapy for HIV-infected individuals. To understand the current subtype distribution and TDR level in Zhejiang, China we performed phylogenetic analysis and genotypic drug resistance testing of treatment-naive HIV-infected individuals. A total of 153 HIV-1 Pol genes were successfully amplified. The distribution of HIV-1 genotypes was as follows: CRF01_AE (43.8%); CRF07_BC (37.9%); subtype B/B' (7.2%); CRF08_BC (5.2%); and others (5.9%). Drug resistance analysis demonstrated that 11.1% of isolates contained at least one NRTI or NNRTI resistance-associated mutations while 2.0% were identified to be resistant to PIs. These findings enhance our understanding of the genetic diversity of HIV-1 strains circulating in Zhejiang and provide some guidelines for HIV initial treatment therapy.

High-throughput sequencing identifies HIV-1-replication- and latency-related miRNAs in CD4+ T cell lines.

MicroRNAs are potent gene expression regulators involved in regulating various biological processes, including host-pathogen interactions. In this study, we used high-throughput sequencing to investigate cellular miRNA signatures related to HIV-1 replication and latent infection in CD4+ T cell lines, which included HIV-1-replicating H9/HTLV-IIIB, HIV-1-latently-infected CEM-Bru cells, and their parental uninfected H9 and CEM-SS cells. Relatively few miRNAs were found to be modulated by HIV-1 replication or latent infection, while the cell-lineage-specific miRNA difference was more pronounced, irrespective of HIV-1 infection. In silico analysis showed that some of our HIV-1 infection-regulated miRNA profiles echoed previous studies, while others were novel. In addition, some of the miRNAs that were differentially expressed between the productively and latently infected cells seemed to participate in shaping the differential infection state. Thus, the newly identified miRNA profiles related to HIV-1 replication and latency provide information about the interplay between HIV-1 and its host.

Multiple amino acid substitutions involved in the adaptation of avian-origin influenza A (H10N7) virus in mice.

To identify substitutions that are possibly associated with the adaptation of avian-origin H10N7 virus to mammals, adaptation of the H10N7 virus in mouse lung was carried out by serial lung-to-lung passage. Genomic analysis of the mouse-adapted virus revealed amino acid changes in the PB2 (E627K), PA (T97I), and HA (G409E) proteins, and this virus was more virulent in mice than the wild-type virus. Our results suggest that these substitutions are involved in the enhancement of the replication efficiency of avian-origin H10N7 virus, resulting in severe disease in mice. Continued poultry surveillance of these substitutions in H10N7 viruses is required.

Isolation and genetic characterization of novel reassortant H6N6 subtype avian influenza viruses isolated from chickens in eastern China.

H6 subtype avian influenza viruses (AIVs) possess the ability to cross the species barrier to infect mammals and pose a threat to human health. From June 2014 to July 2015, 12 H6N6 AIVs were isolated from chickens in live-poultry markets in Zhejiang Province, Eastern China. Phylogenetic analysis showed that these isolates received their genes from H6 and H9N2 subtype AIVs of poultry in China. These novel reassortant viruses showed moderate pathogenicity in mice and were able to replicate in mice without prior adaptation. Considering that novel reassorted H6N6 viruses were isolated from chickens in this study, it is possible that these chickens play an important role in the generation of novel reassorted H6N6 AIVs, and these results emphasize the need for continued surveillance of the H6N6 AIVs circulating in poultry.

Molecular characterization of a novel reassortant H1N2 influenza virus containing genes from the 2009 pandemic human H1N1 virus in swine from eastern China.

Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.

Identify Potential Regulators in HIV-1 Latency by Joint microRNA and mRNA Analysis.

BACKGROUND/AIMS: The main obstacle to cure HIV infection is the existence of long-lasting latent reservoirs. Many efforts have been made to understand basal mechanisms of HIV-1 latency, in which miRNAs play an important role. However, integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking. METHODS AND RESULTS: Global miRNA and mRNA expression was determined by microarrays and quantitative reverse transcription PCR in well-characterized HIV-1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA, mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function network. Our results show that transcription regulation related genes were mostly enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed nuclear transport related pathways were up-regulated in the latency group. Network dynamic analysis highlighted many gene-pairs sharing the largest changes in different HIV-1 infection state. 83.33% miRNA-target pairs were validated against database, and RHOB related genes constitute the interface between HIV-1 latency and replication state. CONCLUSION: We show for the first time a joint miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a dynamic network of potential regulators involving in HIV-1 latency or replication state, and gain new insights into the source messages for affecting HIV-1 latency.

Genetic characterization of natural reassortant H4 subtype avian influenza viruses isolated from domestic ducks in Zhejiang province in China from 2013 to 2014.

The H4 subtype of the influenza virus was first isolated in 1999 from pigs with pneumonia in Canada. H4 avian influenza viruses (AIVs) are able to cross the species barrier to infect humans. In order to better understand the genetic relationships between H4 AIV strains circulating in Eastern China and other AIV strains from Asia, a survey of domestic ducks in live poultry markets was undertaken in Zhejiang province from 2013 to 2014. In this study, 23 H4N2 (n = 14) and H4N6 (n = 9) strains were isolated from domestic ducks, and all eight gene segments of these strains were sequenced and compared to reference AIV strains available in GenBank. The isolated strains clustered primarily within the Eurasian lineage. No mutations associated with adaption to mammalian hosts or drug resistance was observed. The H4 reassortant strains were found to be of low pathogenicity in mice and able to replicate in the lung of the mice without prior adaptation. Continued surveillance is required, given the important role of domestic ducks in reassortment events leading to new AIVs.

Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern China.

Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans.

Characterization of a novel highly pathogenic H5N2 avian influenza virus isolated from a duck in eastern China.

During surveillance for avian influenza viruses (AIVs) in live-poultry markets (LPMs) in eastern China in 2013, one H5N2 AIV was isolated from a duck. Phylogenetic analysis showed that the hemagglutinin of this strain belongs to clade 2.3.4 and received its genes from H5, H3 and H6 AIVs of poultry in China. The virulence of this strain was examined in chickens and mice, and it was found to be highly pathogenic in chickens but demonstrated moderate pathogenicity in mice. These results suggest that active surveillance of AIVs in LPMs should be used in an early warning system for avian influenza outbreaks.

Oral Health Status of Young People Infected with HIV in High Epidemic Area of China.

PURPOSE: This study aimed to understand the oral hygiene habits and oral health status of young people infected with human immunodeficiency virus (HIV) in Henan province of China. METHODS: Randomized stratified cluster sampling strategy was used to select young people who were receiving highly active anti-retroviral therapy (HARRT) from 6 towns. A total of 104 participants were enrolled and divided into 2 groups, adolescence group and young adult group. By face-to-face oral interview and examination, well-trained dentists collected general information, oral hygiene habits and oral health status of the participants. RESULTS: Fifty-eight of them were adolescence group and 46 of them were young adult group. In two groups, most of them brushed their teeth once a day (55.20%, 67.40%), and half of them basically brushed their teeth for 2 minutes (51.7%, 50.0%). Majority of participants did not use dental floss (93.1%,91.3%) and also never visited a dentist (81%,78.3%). One-third of participants had spontaneous bleeding, and about half of them had gingival bleeding when brushed their teeth. The most frequent mucosal disease was oral ulcers. Moreover, the prevalence of caries remained very high in both groups, which was 82.76% and 84.8%, respectively. Most of the participants in both groups had low education level and received less than 9 years of education (65.5%, 63%). CONCLUSION: The participants had poor oral hygiene habits. The economic and education level may associate with the awareness of oral health and care.

Prevalence and Predictors of Syphilis in Female Sex Workers in Eastern China: Findings from Six Consecutive Cross-Sectional Surveys.

PURPOSE: Female sex workers play an important role in transmitting HIV and syphilis from high-risk groups to the general population. However, epidemic trends and risk factors for syphilis in Chinese female sex workers (FSWs) remain unclear. METHODS: Using convenient sampling methods, 2482 FSWs were interviewed and tested for syphilis from 2014 to 2019, all of them were divided into two groups of high-grade FSWs and low-grade FSWs according to service solicited and clients price there were. Demographic data were collected and logistic regression analysis was used to identify risk factors for syphilis. RESULTS: 43.67% of participants have received free condoms, 76.15% of them engaged in peer education of the 2482 FSWs tested for syphilis, 107 (4.31%) were positive. The prevalence of syphilis in high-grade FSWs was significantly lower than that in low-grade FSWs (3.14% and 5.62%, respectively).The overall prevalence of syphilis increased from 3.19% to4.47%. The percentage of FSWs received free condoms and engaged in peer education increased significantly. With upgraded awareness of syphilis, the number of FSWs having protected sex also increased significantly. It is also found that low-grade female sex workers are at greater risk of syphilis than those high-grade ones (odds ratio (OR) = 1.76, 95% CI 1.18-2.63, p < 0.05). CONCLUSION: Great awareness of syphilis and the increased utilization of condom did not reduce the prevalence of syphilis, especially in low-grade FSWs group. More effective integrated interventions should be developed for such populations.

Translation and Validation: Chinese Version of the HIV-Related Social Support Scale.

PURPOSE: Social support is increasingly recognized to be important in care of people living with HIV/AIDS (PLWH), we firstly translate and validate the disease-targeted social support instrument in Chinese and to explore the correlation with WHOQOL-HIV. PATIENTS AND METHODS: We established content validity for HIV-related social support scale (HSSS) and administered the resultant questionnaire to 310 PLWH. Descriptive statistics were generated for each of the variables of general characteristics; student t-test was used to compare the different groups. RESULTS: The HSSS demonstrated a high level of internal consistency, both within each subscale and with the total score; all Cronbach's α values exceeded a priori threshold of ≥0.70. The HSSS cores were positively correlated with WHOQOL-HIV total scores (Pearson correlation: 0.39, P < 0.001). We also found that higher educational level, personal income, CD4 cell count, and shorter duration of antiretroviral therapy are significantly associated with a higher level of social support (P < 0.05). CONCLUSION: Social support may improve quality of life for PLWH, Chinese version of HIV-related social support scale can be used in future clinical practice.

Prevalence of abnormal and borderline electrocardiogram changes in 13, 079 Chinese amateur marathon runners.

BACKGROUND: The 12-lead electrocardiogram (ECG) has been adopted as an important component of preparticipation cardiovascular screening. However, there are still controversies in the screening and few studies with a large sample size have reported the results of ECGs of marathon runners. Therefore, the purpose of this study was to assess the prevalence of normal, borderline, and abnormal ECG changes in marathon runners. METHODS: The 12-lead ECG data of 13,079 amateur marathon runners between the ages of 18 and 35 years were included for analysis. The prevalence of ECG abnormalities among different gender groups was compared with chi-square tests. RESULTS: In terms of training-related changes, sinus bradycardia, sinus arrhythmia, and left ventricular high voltage were found in approximately 15, 5, and 3.28% of the participants, respectively. The incidence of right axis deviation in the marathon runners was 1.78%, which was slightly higher than the incidence of left axis deviation (0.88%). No more than 0.1% of the amateur marathon runners exhibited ST-segment depression, T wave inversion (TWI), premature ventricular contraction, pathologic Q waves, and prolonged QT interval. CONCLUSIONS: Training-related ECG changes, including sinus bradycardia, sinus arrhythmia, and left ventricular high voltage, were common in amateur marathon runners. Most abnormal ECG changes, including ST-segment depression, TWI, premature ventricular contraction, pathologic Q waves, and prolonged QT interval, were infrequently found in amateur marathon runners. The data also suggested Chinese amateur marathon runners may have a relatively lower prevalence of ECG abnormalities than black and white runners.

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

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.

Nanostructured carbon black for simultaneous electrochemical determination of trace lead and cadmium by differential pulse stripping voltammetry.

Nanostructured carbon black (CB) was first employed directly in this paper for the simultaneous electrochemical determination of trace Pb(II) and Cd(II) using differential pulse anodic stripping voltammetry. The morphology and surface properties of conductive CB were characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy and Raman spectroscopy. Special pore structures, as well as surface chemical functional groups, endow CB with excellent catalytic and adsorption properties. Some parameters affecting electrical analysis performance were investigated systematically including deposition time and potential, pH value of solution, volume of suspension, amount of Bi(III) and Nafion solution. CB-Nafion-glassy carbon electrode sensor linear response ranges from 6 to 1000 nM for selective and simultaneous determination. The detection limits were calculated to be 8 nM (0.9 µg l-1) for Cd(II) and 5 nM (1.0 µg l-1) for Pb(II) (S/N = 3) for the electrocatalytic determination under optimized conditions. The method was successfully used to the determination of actual samples and good recovery was achieved from different spiked samples. Low detection limits and good stability of the modified electrode demonstrated a promising perspective for the detection of trace metal ions in practical application.

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

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% (χ2 = 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.

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1.

The differentiation and response ofCD8+ T cells is vital in host defense against human immunodeficiency virus type 1 (HIV-1). MicroRNA (miR)­155 is an important regulator of T cell differentiation. However, the profile of miR-155 in HIV­1 infected individuals and its association with CD8+ T cell differentiation remain to be fully elucidated. The present cross­sectional study was performed involving 63 HIV­1­infected patients undergoing highly active antiretroviral therapy (HAART), 31 HAART­naïve patients and 35 healthy controls. The levels of miR­155 in CD8+ T cells were detected using reverse transcription­quantitative polymerase chain reaction analysis. Subsets of CD8+ T cell differentiation were detected using flow cytometry. The results revealed that the discord controllers and HAART­naïve patients showed higher percentages of effector and effector memory cells, and lower percentages of naïve cells (P<0.05). The levels of miR­155 in CD8+ T cells from the HIV­1­infected patients were higher, particularly in the discord controllers and HAART naïve patients (P<0.01). The expression levels of miR­155 were positively correlated with the percentages of effector and effector memory CD8+ T cells, and negatively correlated with the percentages of naïve and central memory CD8+ T cells (P<0.01). Taken together, these findings suggested that the levels of miR­155 in CD8+ T cells of patients with HIV-1 were increased and asso-ciated with CD8+ T cell differentiation.

The tradition algorithm approach underestimates the prevalence of serodiagnosis of syphilis in HIV-infected individuals.

Currently, there are three algorithms for screening of syphilis: traditional algorithm, reverse algorithm and European Centre for Disease Prevention and Control (ECDC) algorithm. To date, there is not a generally recognized diagnostic algorithm. When syphilis meets HIV, the situation is even more complex. To evaluate their screening performance and impact on the seroprevalence of syphilis in HIV-infected individuals, we conducted a cross-sectional study included 865 serum samples from HIV-infected patients in a tertiary hospital. Every sample (one per patient) was tested with toluidine red unheated serum test (TRUST), T. pallidum particle agglutination assay (TPPA), and Treponema pallidum enzyme immunoassay (TP-EIA) according to the manufacturer's instructions. The results of syphilis serological testing were interpreted following different algorithms respectively. We directly compared the traditional syphilis screening algorithm with the reverse syphilis screening algorithm in this unique population. The reverse algorithm achieved remarkable higher seroprevalence of syphilis than the traditional algorithm (24.9% vs. 14.2%, p < 0.0001). Compared to the reverse algorithm, the traditional algorithm also had a missed serodiagnosis rate of 42.8%. The total percentages of agreement and corresponding kappa values of tradition and ECDC algorithm compared with those of reverse algorithm were as follows: 89.4%,0.668; 99.8%, 0.994. There was a very good strength of agreement between the reverse and the ECDC algorithm. Our results supported the reverse (or ECDC) algorithm in screening of syphilis in HIV-infected populations. In addition, our study demonstrated that screening of HIV-populations using different algorithms may result in a statistically different seroprevalence of syphilis.

Identification of a Novel HIV Type 1 Recombinant Form (CRF01_AE/CRF07_BC) in Men Who Have Sex with Men in Zhejiang, China.

The prevalence of HIV-1 is increasing rapidly among the population of men who have sex with men (MSM) in China. Here, we report a novel HIV type 1 recombinant form consisting of CRF01_AE and CRF07_BC detected in a male patient through homosexual behavior. A phylogenic analysis revealed that this unique recombinant form (URF) exhibits a complex genomic structure with three CRF07_BC regions inserted into the CRF01_AE backbone. Recently, several second-generation recombinant forms (e.g., CRF01_AE/CRF07_BC) have been identified among MSM in China. The emergence of such URFs highlights the complexity of the HIV-1 epidemic among this population. Therefore, further molecular epidemiological investigation is required to track the genetic evolution of HIV-1 strains.