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JinJian Yao,1,&ast; Hangfei Wang,2,&ast; Weiling Yu,3,&ast; Yimin Li,4 Zhiqian Luo,2 Biao Wu,5 Wei Zhang,6 Xiaoran Liu,2 Chuanzhu Lv6,7 1Emergency Center, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 3Oncology Department, Haikou City People’s Hospital, Haikou, Hainan, People’s Republic of China; 4Department of General Surgery, Yang Jiang Hospital of Qiongzhong, Qiongzhong, Hainan, People’s Republic of China; 5Department of Infectious Disease, Hainan General Hospital Affiliated to Hainan Medical University, Haikou, Hainan, People’s Republic of China; 6Emergency and Trauma College of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 7Key Laboratory of Emergency and Trauma, Ministry of Education of Hainan Medical University, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoran LiuDepartment of Emergency, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of ChinaTel +8613118901829Email liuxiaoran3192@163.comChuanzhu LvKey Laboratory of Emergency and Trauma, Ministry of Education of Hainan Medical University, Haikou, Hainan, People’s Republic of ChinaTel +8617789830771Email lvchuanzhu677@126.comIntroduction: Close contacts of individuals with COVID-19 may directly gain immunity against SARS-CoV-2 despite lacking a detectable infection. This study examined SARS-CoV-2-specific antibodies levels based on gender, age, and exposure source in close contacts of individuals with COVID-19 and compared antibody levels to patients with an asymptomatic or symptomatic COVID-19 infection.Methods: Two patients had confirmed COVID-19 infections at a community hospital in Qiongzhong, Hainan province. Contact tracing identified all individuals in the community who had been exposed to the two patients during the 14 days before their diagnoses. Close contacts quarantined for 14 days, underwent two SARS-CoV-2 tests, and were screened for SARS-CoV-2-specific antibodies at 7 and 12 weeks after the end of quarantine. SARS-CoV-2-specific antibody levels for the close contacts were compared to those for patients with an asymptomatic or symptomatic COVID-19 infection at 7 and 12 weeks after their diagnoses.Results: Contact tracing identified 10,573 individuals in the community, including 360 (3.4%) close contacts. At 7 weeks, 30 (8.33%) close contacts were positive for SARS-CoV-2-specific antibodies (IgG, n = 26 [7.22%]; IgM, n = 4 [1.11%]), which were lower than the proportion of patients with an asymptomatic (IgG, 100% [12/12]) or symptomatic (IgG, 93.6% [44/47]) COVID-19 infection. SARS-CoV-2-specific IgM antibody levels were significantly higher in close contacts who were exposed through a relative compared to a doctor–patient relationship (P = 0.032). SARS-CoV-2-specific IgG antibody levels were significantly higher in close contacts aged < 18 years vs 18– 64 years (P = 0.014). At 12 weeks, SARS-CoV-2-specific IgG antibody levels among close contacts were significantly lower than among patients with an asymptomatic (P = 0.004) or symptomatic COVID-19 infection (P < 0.001).Conclusion: Immune protection conferred by close contact is short term and unlikely to contribute to herd immunity. There remains an unmet public health need for mass vaccination of populations to increase levels of protective antibodies and achieve and maintain herd immunity.Keywords: SARS-CoV-2, COVID-19, antibody, close contact

BackgroundSince January 2020, coronavirus disease 2019 (Covid-19) has spread rapidly and developing the pandemic model around the world. Data have been needed on the clinical characteristics of the affected patients in an imported cases as model in island outside Wuhan.MethodsWe conducted a retrospective study included all 168 confirmed cases of Covid-19 in Hainan province from 22 January 2020 to 13 March 2020. Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, radiological and laboratory data.ResultsOf 168 patients, 160 have been discharged, 6 have died and 2 remain hospitalized. The median age was 51.0 years and 51.8% were females. 129 (76.8%) patients were imported cases, and 118 (70.2%), 51 (30.4%) and 52 (31%) of patients lived in Wuhan or traveled to Wuhan, had contact with Covid-19 patients, or had contact with Wuhan residents, respectively. The most common symptoms at onset of illness were fever (65.5%), dry cough (48.8%) and expectoration (32.1%). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (60.2%). The elderly people with diabetes, hypertension and CVD are more likely to develop severe cases. Follow-up of 160 discharged patients found that 20 patients (12.5%) had a positive RT-PCR test results of pharyngeal swabs or anal swabs or fecal.ConclusionsIn light of the rapid spread of Covid-19 around the world, early diagnosis and quarantine is important to curb the spread of Covid-19 and intensive treatments in early stage is to prevent patients away from critical condition.

Objective We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 (RTEL1), which has been associated with telomere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population. Methods In a case-control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. Results In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10-0.82; P=0.02). In the genetic model analysis, we found that the "C/C" genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13-0.86; P=0.022) and recessive model (OR =0.32; 95% CI =0.12-0.80; P=0.009). Conclusion Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population.

Objectives We investigated prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in a population of Hlai (the Li) ethnicity, a major minority, in Qicha Town, Changjiang County, Hainan Province, PRC, during 2014. Methods All residents at the age of 40 years or older were interviewed with standardized questionnaires. Spirometry was performed to measure the possible airflow limitation. According to the GOLD criteria, post bronchodilator FEV1/FVC 0.05, suggesting that the sex did not affect the COPD prevalence in the investigated samples, but age (OR = 1.096), expectoration (OR = 87.917), locomotor activity limitation (OR = 3.908) and frequency of respiration (OR = 2.512) were risk factors and associated with the development of COPD. Notably, although the tobacco smoker in male and female COPD patients were 48.6% (54/111) and 4.0% (4/101), respectively, passive smokers in female with COPD were 45.6% (46/101). Conclusion In the Hlai population aged ≥40 years, the COPD prevalence was 5.07%. Smoking, age, expectoration, locomotor activity limitation and frequency of respiration were risk factors of COPD in Hlai ethnicity.

Objectives The present study aimed to screen members of the Li nationality in southern China for genotype frequencies of VIP variants and to determine differences between the Li ethnicity and global human population samples in HapMap. Methods In this study, we genotyped 77 very important pharmacogenetic (VIP) variants selected from the pharmacogenomics knowledge base (PharmGKB) in members of the Li population and compared our data with other eleven populations from the HapMap data set. Results Our results showed that VDR rs1540339, VKORC1 rs9934438, and MTHFR rs1801133 were most different in Li compared with most of the eleven populations from the HapMap data set. Furthermore, population structure and F-statistics (Fst) analysis also showed differences between the Li and other HapMap populations, and the results suggest that the Li are most genetically similar to the CHD population, and the least similar to the YRI in HapMap. Conclusions The findings of our study complement the pharmacogenomics database with information on members of the Li ethnicity and provide a stronger scientific basis for safer drug administration, which may help clinicians to predict individual drug responses, thereby avoiding the risk of adverse effects and optimizing efficacy in this population.

Aim: Previous research has suggested that Ephrin receptor A3 (EphA3) plays signaling roles in the processes of inflammation by regulating lymphocyte migration and proliferation. In this study, we investigated whether the EphA3 gene polymorphism was associated with disease progression of chronic hepatitis B virus (HBV) infection. Methods: The EphA3 variant rs9310117 was genotyped in 1245 unrelated Han Chinese HBV carriers including 800 cases and 445 controls. χ2 test was used to examine the difference in allele frequencies and genotype distributions between groups. The association between the polymorphism and disease progression of HBV infection was conducted by unconditional logistic regression analysis. Results: Statistical analysis revealed that the genetic variant was significantly associated with the occurrence of chronic severe hepatitis B (CSHB). We observed that subjects bearing at least one T allele (C/T or T/T genotype) had a decreased susceptibility to chronic severe hepatitis B compared with those bearing C/C genotype (P = 0.003, odds ratio = 0.560; 95% confidence interval, 0.381–0.824, recessive model). Genotype C/T had also been confirmed to protect subjects from suffering chronic severe hepatitis B (P = 0.001, odds ratio = 0.498; 95% confidence interval, 0.330–0.752, additive model). Conclusion: Our results suggest that the genetic alteration at EphA3 locus plays a role in the occurrence of chronic severe hepatitis B.

Transforming growth factor (TGF) β1 plays a critical role in liver fibrosis. Previous studies demonstrated embryonic liver fodrin (ELF), a β-spectrin was involved in TGF-β/Smad signalling pathway as Smad3/4 adaptor. Here we investigate the role of ELF in pathogenesis of liver cirrhosis. In carbon tetrachloride (CCl4)-induced mice model of liver cirrhosis, ELF is up-regulated in activated hepatic stellate cells (HSCs), and down-regulated in regenerative hepatocytes of cirrhotic nodules. In activated HSCs in vitro, reduction of ELF expression mediated by siRNA leads to the inhibition of HSC activation and procollagen I expression. BrdU assay demonstrates that down-regulation of ELF expression does not inhibit proliferation of activated HSCs in vitro. Immunostaining of cytokeratin 19 and Ki67 indicates that regenerative hepatocytes in cirrhotic liver are derived from hepatic progenitor cells (HPC). Further study reveals that HPC expansion occurs as an initial phase, before the reduction of ELF expression in regenerative hepatocytes. Regenerative hepatocytes in cirrhotic liver show the change in proliferative activity and expression pattern of proteins involved in G1/S transition, which suggests the deregulation of cell cycle in regenerative hepatocytes. Finally, we find that ELF participates in TGF-β/Smad signal in activated HSCs and hepatocytes through regulating the localization of Smad3/4. These data reveal that ELF is involved in HSC activation and the formation of regenerative nodules derived from HPC in cirrhotic liver.

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928-3.760; P=6.2×10(-9); additive model) and the replication phase (OR, 1.490; 95% CI, 1.104-2.012; P=9.0×10(-3); additive model). These two SNPs were in strong linkage disequilibrium with D'=0.99 and r (2)=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538-2.545; P=8.1×10(-8)). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

A study with two cross-sectional surveys in two consecutive years was conducted in Shanghai, China to examine the seroprevalence of herpes simplex virus type 2 (HSV-2), syphilis and HIV among female sex workers (FSW). A total of 793 FSW participated in the survey, 382 in 2008 only, 382 in 2009 only, and 29 in both 2008 and 2009. The majority of them were less than 30 years and two-thirds were married. All were migrants and a half was from rural areas. Some of them have stayed in Shanghai and engaged in commercial sex for more than two years. Their knowledge of HIV/AIDS was limited. Condom use was not common for both marital sex and non-commercial extramarital sex but fairly frequent for commercial sex. Two-percent were using drugs in the past year. Nearly one quarter reported having syndromes of sexually transmitted diseases (STD) in the past year, with a substantial proportion of them untreated or treated inappropriately. No one was HIV-infected. The overall HSV-2 seroprevalence was 47.3% (375/793), 45.5% (187/411) in 2008 and 50.1% (206/411) in 2009. The overall prevalence of syphilis was 4.5% (36/793), 7.0% (29/411) in 2008 and 2.4% (10/411) in 2009. Multiple logistic regression analyses indicated that HSV-2 infection was statistically associated with age, type of working venue, origin, and period of staying in Shanghai; whereas syphilis infection was statistically associated with year of participation and smoking status. In conclusion, HSV-2 is highly prevalent among FSW in Shanghai, with a relatively low prevalence of syphilis. The currently low HIV epidemic in this population provides a window of opportunity to implement tailored HIV/STD prevention and control efforts targeting them, with particular attentions to large numbers of HSV-2-infected FSW and their clients.

Knowing one’s HIV status is the first step to accessing care and preventing further infection (World Health Organization [WHO, 2002). This knowledge enables the tested individual to initiate or maintain safer behaviors to prevent acquisition of HIV and other sexually transmitted diseases (STDs), and if testing positive, to prevent infecting others and to gain early access to HIV-specific care, treatment and support (Kawichai et al., 2004; Otten, Zaidi, Wroten, Witte, & Peterman, 1993; Weinhardt, Carey, Johnson, & Bickham, 1999; WHO, 2002). Voluntary counseling and testing (VCT) has been demonstrated as one of the most effective strategies in this regards (Holtgrave & McGuire, 2007; Robles, Matos, Colon, Marrero, & Reyes, 1996; Voluntary HIV Counseling and Testing Efficacy Study Group, 2000). During the last 5 years, China has established 4,293 VCT clinics all over the country (China State Council AIDS Working Committee Office [CSCAWCO] & UN Theme Group on AIDS in China, 2007). However, among 700,000 people living with HIV in China, the majority still did not know their HIV infection status (CSCAWCO & UN Theme Group on AIDS in China, 2007). This underscores the need for increasing acceptance and utilization of HIV testing services in China. Such need might be particularly relevant for rural-to-urban migrants as they have played important roles in HIV transmission in China (He et al., 2006; He, Wong, Huange, Ding, et al., 2007; He, Wong, Huang, Thompson, & Fu, 2007; Li et al., 2004; Liu et al., 2005; Qian, Vermund, & Wang, 2005), and they have no entitlement to urban health cares and services accorded to most urban dwellers owing to their nonurban residency (Wong, Li, & Song, 2007). Public health practitioners have informally observed that the number of individuals voluntarily receiving HIV counseling and/or testing is unexpectedly low in China. Moreover, none of these VCT sites and promotion programs has been specifi-cally designed and developed for migrants and very few migrants have ever received an HIV test and face-to-face counseling. Therefore, we conducted a cross-sectional survey among rural migrants in Shanghai, the most populous and economically developed city in China, to better understand HIV/AIDS knowledge, attitudes and awareness, and VCT-related knowledge, attitudes, and practices (KAP) among them. A rural migrant was defined as someone born and registered as a permanent resident in a rural area but who worked in Shanghai.

Objective To study the risk factors for chronic obstructive pulmonary disease (COPD) in Li population in Hainan province, People’s Republic of China. Methods Li people above 40 years of age from Hainan were chosen by stratified random cluster sampling between 2012 and 2014. All participants were interviewed with a home-visiting questionnaire, and spirometry was performed on all eligible participants. Patients with airflow limitation (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] 20 cigarettes/day, smoking for 40 years or more, second-hand smoking, recurrent respiratory infections, and induced cough were risk factors for COPD, whereas high BMI, high education level, and presence of ventilated kitchen were protective factors. Subsequent multivariate logistic regression model further demonstrated that aging, low BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory tract infections were high-risk factors for COPD in the Li population. Conclusion The incidence of COPD has a strong correlation with age, BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory infections, suggesting they were high-risk factors for COPD in Li population.

We investigated prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in a population of Hlai (the Li) ethnicity, a major minority, in Qicha Town, Changjiang County, Hainan Province, PRC, during 2014.All residents at the age of 40 years or older were interviewed with standardized questionnaires. Spirometry was performed to measure the possible airflow limitation. According to the GOLD criteria, post bronchodilator FEV1/FVC 70% was defined as COPD. Case-control study was used to screen the risk factors by analyzing COPD group (212 cases) and non-COPD control group (236 cases). Single factor analysis and multiple factor logistic regression analysis were used as statistical methods.The prevalence of COPD in the residents at the age of 40 years or older of Hlai community was 5.07% (286/5637) (95% CI = 0.045-0.057). In the logistic regression analysis, the COPD prevalence was 5.07% (147/2901) in men and 5.08% (139/2736) in women, respectively, with odds ratio (OR) 1.003, 95% CI 0.790-1.272 and P 0.05, suggesting that the sex did not affect the COPD prevalence in the investigated samples, but age (OR = 1.096), expectoration (OR = 87.917), locomotor activity limitation (OR = 3.908) and frequency of respiration (OR = 2.512) were risk factors and associated with the development of COPD. Notably, although the tobacco smoker in male and female COPD patients were 48.6% (54/111) and 4.0% (4/101), respectively, passive smokers in female with COPD were 45.6% (46/101).In the Hlai population aged ≥40 years, the COPD prevalence was 5.07%. Smoking, age, expectoration, locomotor activity limitation and frequency of respiration were risk factors of COPD in Hlai ethnicity.

CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3’UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.

Background: The frequencies of Cytochrome P450 2C9 (CYP2C9) genotypes were various between populations. The aim of this study was to investigate the frequencies of the major variants of the CYP2C9 in Chinese Li minority populations. Methods: The promoter, exons and surrounding introns, and 3’-untranslated region of the CYP2C9 gene was detected by DNA sequencing to investigate in 100 unrelated healthy Chinese Li subjects. The protein function prediction was used the online tools: Sorting Intolerant From Tolerant (SIFT) and Phenotyping Version 2 (PolyPhen-2). The comparison of CYP2C9 allele frequencies in different populations were analyzed by Chi-square (χ2) test. Linkage disequilibrium (LD) analysis was performed using Haploview software. Results: We identified 17 different CYP2C9 single nucleotide polymorphisms (SNPs) in the Li population, including two missense mutations (3549 G > A and 42614 A > C) and two silent mutations (3514 T > Cand 50298A > T). The protein function prediction revealed the two missense mutations result in protein damaging. In addition, we detected the allele frequencies of CYP2C9*1, CYP2C9*3 and CYP2C9*42 were 98%, 1%, and 1%, respectively. Finally, we compared three major allelic frequency (CYP2C9*1, CYP2C9*2, and CYP2C9*3) between Li and other populations. We found that our results were similar to East Asians and Africans.

Yipeng Ding,1,* Danlei Yang,2,3,* Long Zhou,4 Junxu Xu,5 Yu Chen,5 Ping He,1 Jinjian Yao,1 Jiannan Chen,1 Huan Niu,1 Pei Sun,1 Tianbo Jin4 1Department of Emergency, People’s Hospital of Hainan Province, Haikou, Hainan, 2Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, 3Department of Science and Technology, Huazhong University, Wuhan, 4School of Life Sciences, Northwest University, Xi’an, 5Department of Respiration Emergency, The Third People’s Hospital of Haikou, Haikou, Hainan, People’s Republic of China *These authors contributed equally tothis work Background: It is known that the contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations. Further, previous studies involving various ethnic groups have revealed associations between COPD and genetic polymorphisms in families with sequence similarity 13, member A (FAM13A), micro-RNA 2054 (MIR2054), SET domain containing protein 7 (SETD7), ring finger protein 150 (RNF150), hedgehog interacting protein (HHIP), and vascular endothelial growth factor A (VEGFA). Our objective was to explore the association between these gene polymorphism and COPD in members of Chinese Li minority population.Materials and methods: The Chinese Li population case–control study was conducted to assess genetic associations with COPD risk. Seven single nucleotide polymorphisms (SNPs) located on chromosome 4, including FAM13A, MIR2054, SETD7, RNF150, and HHIP, and nine SNPs in the VEGFA gene were genotyped among 234 cases and 240 controls using Sequenom Mass-ARRAY® platform. Linkage disequilibrium (LD) analysis was performed using Haploview software and the associations of the SNP frequencies with COPD were analyzed using chi-square (χ2) tests, genetic models analysis, and haplotype analysis.Results: By χ2 we found the minor allele “G” of rs17050782 was with increased COPD risk in allele model. In genetic models, we found the minor allele of rs7671167 (P=0.028 by dominant model) and rs17050782 (P=0.008 by recessive model) was associated with the increased risk of COPD disease. Likewise, an increased risk of developing COPD was associated with the “GGCGC” haplotype of VEGFA (odds ratio =1.48, 95% confidence interval =1.02–2.12, P=0.037).Conclusion: Our results were the first time to reveal that SNPs from FAM13A (rs7671167), SETD7 (rs17050782), and a haplotype of VEGFA (“GGCGC”) are potential susceptibility loci associated with increased COPD risk in Chinese Li minority population. Keywords: chronic obstructive pulmonary disease, case–control study, single nucleotide polymorphism, Chinese Li minority population

To investigate the RNA interference (RNAi) effect induced by vector-derived small interfering RNA (siRNA) targeting the three gatekeeper genes (Rad52, Ku70, Ku80) and screen the more effective target sites from candidates for further research, by using siRNA design tools online, we selected 2 candidate sequences directed to every gatekeeper gene. According to the sequences, six vector-derived siRNAs (denoted psiRNA1-6) and one mocking psiRNA7 were constructed. Among them, psiRNA1 and psiRNA2 targeted Rad52, psiRNA3 and psiRNA4 to Ku70, psiRNA5 and psiRNA6 to Ku80. The mocking psiRNA7 was used as control. After sequence identification, the seven plasmids were transfected into HepG2 cell line. siRNA-induced silencing of gatekeeper genes was determined by using RT-PCR at RNA level and Western Blot at protein level. The results showed that the six plasmids specifically targeting the coding region of gatekeeper genes were successfully designed and constructed. To some extent, the six plasmids could reduce the expression of target gene. Comparatively, the plasmid-derived siRNA psiRNA1, psiRNA4 and psiRNA5 were more effective than their counterparts. The results suggest that the gene silencing efficiency of siRNA is different, depending on their targeted region, and siRNA may provide us with practical tools for further study on the three gatekeeper genes, i.e. Rad52, Ku70, Ku80.

To assess the association of rs9272346 polymorphism of HLA-DQA1 gene with clinical outcome of hepatitis B virus (HBV) infection in ethnic Han population from Hubei, China.A case-control study was conducted, which have involved 1028 unrelated subjects including 238 asymptomatic HBV carriers (AHC), 173 acute liver failure (ALF), 292 liver cirrhosis (LC) and 325 hepatocellular carcinoma (HCC). Genotypes of rs9272346 were determined by real-time polymerase chain reaction with a TaqMan MGB probe. Statistical results were analyzed using Chi square test, student's t test and unconditional logistic regression.No significant differences were detected in the frequencies of G allele between ALF, LC, HCC and AHC groups (P= 0.312, 0.314, 0.264). Compared with the AA genotype, the GG and GA genotypes were not associated with the patients groups under the dominant model: ALF group vs. AHC group (adjusted OR= 1.08, 95%CI: 0.7-1.68), LC group vs. AHC group (adjusted OR= 1.11, 95%CI: 0.87-1.26), HCC group vs. AHC group (adjusted OR= 0.93, 95%CI: 0.65-1.33). For women, the GG and GA genotypes have conferred a protective effect for the outcome of ALF (OR= 0.30, 95%CI: 0.1-1.87).Our results suggested that rs9272346 polymorphism of HLA-DQA1 may not independently influence the outcome of HBV infection in ethnic Han Chinese in Hubei, while the GG and GA genotypes may confer a protective effect against ALF in women.

The host genetic compound plays a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease. In this report, we explored whether the intronic polymorphism rs3820998 of the TANK gene was associated with outcomes of HBV infection by binary logistic regression analysis. A total of 1305 unrelated Han Chinese patients recruited from Wuhan, including 180 acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients, 331 HBV-related liver cirrhosis (LC) patients, 308 HBV-related hepatocellular carcinoma (HCC) patients, and 486 asymptomatic HBV carriers (AsC) were genotyped using the TaqMan probe method. Logistic analysis revealed that the single-nucleotide polymorphism (SNP) rs3820998 was significantly associated with susceptibility to ACLF-HBV (dominant model, OR 0.643, 95% CI 0.428,0.964, p=0.033; additive model, OR 0.640, 95% CI 0.414,0.990, p=0.045), and LC (recessive model, OR 0.398, 95% CI 0.164,0.966, p=0.042; additive model, OR 0.379, 95% CI 0.155,0.928, p=0.034). These results indicate that the GT variant is a protective factor in the development of ACLF-HBV and LC, and that the SNP rs3820998 in the TANK gene may play a role in mediating susceptibility to ACLF-HBV and LC in a Chinese Han population.

Host genetics play a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. To identify novel susceptibility loci to HBV progression, we carried out a genome-wide association study with DNA pooling. This study assessed the relationship between 8 highly-ranked SNPs selected from our DNA pool and disease progression of HBV infection in two independent case-control studies. The first population included 628 asymptomatic HBV carriers (AsC) and 1729 progressed HBV carriers recruited from Hubei Province in south China. The second population was composed of 226 AsC and 215 progressed HBV carriers recruited from Shandong Province in north China. Of the 8 SNPs, variant rs11866328 (G/T), located in the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene, was replicated and had significant associations with disease progression of HBV infection in the DNA pooling stage both in the Hubei (OR 1.65; 95% CI 1.34,2.02; p=1.96 × 10(-6); additive model), and in the Shandong (OR 1.73; 95% CI 1.14,2.65; p=1.00×10(-2); additive model) population. Polymorphism rs11866328 in the GRIN2A gene might be a genetic variant underlying the susceptibility of HBV carriers to disease progression.

BackgroundHuman leukocyte antigen DP (HLA-DP) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations.Methodology/principal findingsTwo HLA-DP variants rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP locus) were genotyped in three independent Han cohorts consisting of 2 805 cases and 1 796 controls. By using logistic regression analysis, these two SNPs in the HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in Han Chinese populations (P = 0.021∼3.36×10(-8) at rs2395309; P = 8.37×10(-3)∼2.68×10(-10) at rs9277535). In addition, the genotype distributions of both sites (rs2395309 and rs9277535) were clearly different between southern and northern Chinese population (P = 8.95×10(-5) at rs2395309; P = 1.64×10(-9) at rs9277535). By using asymptomatic HBV carrier as control group, our study showed that there were no associations of two HLA-DP variants with HBV progression (P = 0.305∼0.822 and 0.163∼0.881 in southern Chinese population, respectively; P = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively).ConclusionsOur results confirmed that two SNPs (rs2395309 and rs9277535) in the HLA-DP loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression.

In order to screen potential mRNA locations of P gene in which targeting siRNAs can effectively inhibit HBV expression, 5 recombinant plasmids containing 4 targeting-specific siRNA fragments and a control were prepared and transfected into 2.2.15 cells respectively. The expression levels of HBx mRNA, HBs mRNA and HBc mRNA were detected by RT-PCR. The concentrations of the hepatitis B virus antigens, including HBsAg and HBeAg harvested from the culture supernatant of transfected 2.2.15 cells, were measured by ELISA. X protein was tested by Western blot. The results showed that four siRNAs against distinct mRNA locations of HBV polymerase gene had different inhibitory effects on their targeted mRNA. The plasmid-derived psiRNA1 and psiRNA2 could effectively inhibit the transcription and translation of HBs gene, whereas the inhibitory efficiency of psiRNA3, psiRNA4 for HBe gene was much higher than that of psiRNA1 and psiRNA2. In comparison to the rest of psiRNAs in this study, psiRNA4 was the most effective to suppress the transcription and translation of HBx. It is suggested that siRNA can be considered as a powerful therapeutic agent for reducing HBV expression. The siRNAs against HBV polymerase are effective largely depending on the location of targeted sites. To enhance inhibitory efficiency, hunting for high effective target in polymerase gene is necessary and feasible.

Yipeng Ding,1,* Junxu Xu,2,* Jinjian Yao,1 Yu Chen,2 Ping He,1 Yanhong Ouyang,1 Huan Niu,1 Zhongjie Tian,1 Pei Sun1 1Department of Emergency, People’s Hospital of Hainan Province, 2Department of Respiratory, The Third People’s Hospital of Haikou, Haikou, Hainan, People’s Republic of China *These authors contributed equally tothis work Objective: To study the risk factors for chronic obstructive pulmonary disease (COPD) in Li population in Hainan province, People’s Republic of China.Methods: Li people above 40 years of age from Hainan were chosen by stratified random cluster sampling between 2012 and 2014. All participants were interviewed with a home-visiting questionnaire, and spirometry was performed on all eligible participants. Patients with airflow limitation (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] 20 cigarettes/day, smoking for 40 years or more, second-hand smoking, recurrent respiratory infections, and induced cough were risk factors for COPD, whereas high BMI, high education level, and presence of ventilated kitchen were protective factors. Subsequent multivariate logistic regression model further demonstrated that aging, low BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory tract infections were high-risk factors for COPD in the Li population.Conclusion: The incidence of COPD has a strong correlation with age, BMI, biomass smoke, >20 cigarettes/day, and recurrent respiratory infections, suggesting they were high-risk factors for COPD in Li population. Keywords: chronic obstructive pulmonary disease, epidemiology, survey, Li population