Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10–15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular ...carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.
The Rhesus (Rh) blood group is a significant and complicated biological system in humans. Incompatible transfusion or pregnancy with Rh antigens can lead to the production of alloantibodies, among ...which the anti-E antibody is prevalent. The relationship between Anti-E antibody and HLA-II gene polymorphism in Chinese pregnant women is worth exploring. Our aim in this study was to verify the correlation between HLA-II gene polymorphisms and RhE alloimmunization in pregnant Chinese women through HLA-II typing and DR-RhE structural prediction. In total, 94 anti-E-negative pregnant women and 103 anti-E-positive pregnant women were enrolled from Southwest China Second Hospital, and HLA-II genotyping was performed using next-generation sequencing. NetMHCpan software was used to predict the binding of E -derived anchoring peptides to HLA-DRB1 molecules. AlphaFold was used to analyze the differences in antigen presentation based on the structure of major histocompatibility complex peptides. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 haplotype showed a significant positive association with anti-E. One E-derived anchoring peptide (219FWPSVNSPL227) was predicted to bind to the HLA-DRB1*09:01 molecule. The interaction between the 60Ser of DR9 and 226pro of RhE comprised one hydrogen bond. This study demonstrated that HLA-II haplotypes are associated with allo-anti-E antibodies in pregnant women from Sichuan Province, China. The HLA-DRB1*09:01-DQA1*03:02-DQB1*03:03 phenotype may enhance the formation of anti-E alloantibodies, and the HLA-DRB1*09:01 molecule may play a key role in alloimmunity.
Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.
This ...study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case-control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance.
We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02.
DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).
Chronic hepatitis B virus (HBV) infection is influenced by both viral and host factors. In genome‐wide association studies, the human leucocyte antigen HLA‐DPA1 and related polymorphism rs3077 were ...found to be associated with susceptibility to and spontaneous clearance of HBV infection. Here, we evaluated the association between HLA‐DPA1 mRNA expression and the risk of HBV infection. HLA‐DPA1 and rs3077 polymorphisms were investigated in 169 patients with chronic HBV and 217 healthy controls (HCs) from Sichuan Han blood donors using sequence‐based typing and meta‐analysis for HLA‐DPA1 alleles. HLA‐DPA1 mRNA levels were measured by real‐time polymerase chain reaction. The results showed that HLA‐DPA1 and rs3077 were associated with HBV infection in the Sichuan population. Rs3077T and DPA1*01:03 played protective roles in HBV infection, and rs3077C and DPA1*02:02 increased susceptibility to HBV infection. We found that the HLA‐DPA1 mRNA expression was decreased in the CHB group; in particular, the 3077CT, 3077TT, DPA1*01:03 and DPA1*02:01 alleles showed a significant decrease. Our results demonstrated, for the first time, that expression of HLA‐DPA1 alleles and rs3077 affected the risk of HBV infection. Genotypes with lower HLA‐DPA1 expression had a greater susceptibility to HBV infection. Thus, further independent studies are needed to strengthen the associations of these polymorphisms with susceptibility to and clearance of HBV infection in Chinese populations.
There are few data available on the prevalence, incidence, and residual risk of transfusion-transmitted HBV (TT-HBV) infections among Chinese blood donors. This study investigated the demographic ...characteristics of blood donors, as well as the prevalence, incidence, and residual risk (RR) of TT-HBV infections in six large blood centers in different regions of China.
The demographic characteristics and HBV screening test results of blood donors from six blood centers in different regions in China were collected and analyzed. The hepatitis B surface antigen (HBsAg) yield approach was used to estimate the incidence of HBV. Then, the RR of TT-HBV infections was evaluated using the incidence-window period model.
The majority of donors were between 18 and 35 years old (including 35), with the exception of the Changzhi Blood Center where a majority of donors were between 35 and 55 years old (including 55). The prevalences of HBV were 0.13%, 0.078%, 0.16%, 0.07%, 0.20%, 0.25% in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. The estimated corresponding incidences were 213.44, 161.59, 989.80, 278.05, 125.31 and 352.19 per 10
person-years. Using an infectious window period of 59 days, the RR for HBV was estimated to be 34.14, 25.85, 158.35, 44.48, 20.04 and 56.35 per 10
person-years in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively.
Despite the introduction of more sensitive assays in blood screening, our data revealed that the current residual risk of TT-HBV infection was still high (overall 56.53 per 10
py). A continuous monitoring of the residual risk of transfusion-transmitted infections is crucial for safe blood management.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of the HLA-DRB1 and HLA-DQB1 genes in the antibody response to hepatitis B (HB) vaccine has been well established; however, the involvement of the HLA-DPB1 allele in the HB vaccine immune ...response remained to be clarified by a systematic review.
A meta-analysis was performed in which databases were searched for relevant studies published in English or Chinese up until June 1, 2020. Six studies were identified and a total of 10 alleles were processed into statistical processing in this meta-analysis.
Three thousand one hundred forty four subjects (including 2477 responders and 667 non-responders) were included in this research. Alleles HLA-DPB1∗02:02, DPB1∗03:01, DPB1∗04:01, DPB1∗04:02, and DPB1∗14:01 were found to be associated with a significant increase in the antibody response to HB vaccine, and their pooled odds ratios (ORs) were 4.53, 1.57, 3.33, 4.20, and 1.79, respectively; whereas DPB1∗05:01 (OR = 0.73) showed the opposite correlation.
These findings suggested that specific HLA-DPB1 alleles are associated with the antibody response to HB vaccine.
The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly ...basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.
Abstract Since the establishment of People's Republic of China in 1949, the Chinese government has encountered several catastrophes related to transfusion transmitted diseases. The government's ...increasing attention to blood safety has prompted the initiation of a series of policies and measures which have enhanced the level of safety for the blood supply, and met the basic clinical demands of blood for 1.3 billion people in the country. Blood donation screening strategies in China are predominantly comprised of donor screening and donor testing. Donor screening includes selection of low risk blood donors by the use of a donor history questionnaire, pre-donation physical examination and initial rapid donor testing. Donor testing includes direct pathogen detection and serology tests. The year 1998 marked the most transformative change in blood donor selection and screening policies in China. Before 1998, paid donation was the predominant mode of blood donation. Donor screening and donor testing were conducted before donation, and only those who were eligible were allowed to donate. To ensure the safety of blood, donor testing was performed again after donation. After the implementation of the Blood Donation Law in 1998, in order to promote voluntary and unpaid donation, pre-donation donor testing was eliminated to reduce the amount of waiting time and to provide a more convenient donation experience for blood donors. However, it is the national requirement that donated blood should undergo two rounds of testing using different equipments or reagents, conducted by different personnel. Donor selection has transitioned from paid donation and obligatory donation to voluntary donation with fixed volunteer groups, as the latter mode of donation provides the lowest risks. Donations are currently screened for syphilis, HCV, HIV, and HBV. Units, previously typed only for ABO, are now routinely tested for both ABO and Rh(D). Innovations in testing technologies and methods have also brought changes to screening parameters. For instance, screening for HBV pathogens evolved from the early use of hemagglutination method, to the later use of radioimmunoassay, independent enzyme linked immunosorbent assay (ELISA), and now the widespread application of nucleic acid test (NAT). Since 2010, the Chinese government has established NAT testing capacity in several blood centers; and in 2015, the government invested 900 million dollars on the nationwide expansion of NAT testing. Although the Chinese government has worked to enhance blood safety, many challenges remain. Concern exists for rising rates of HIV infection. The existence of occult HBV infection (OBI) and the transmission of emerging blood-borne diseases continue to challenge the safety of the blood supply.
To assess the association of single nucleotide polymorphisms (SNPs) of dual specificity phosphatase 9 (DUSP9) gene rs5945326 locus with gestational diabetes mellitus (GDM).
Genotypes for the ...rs5945326 locus were determined for 206 pregnant women with GDM (GDM group) and 189 unaffected pregnant women (control group). Allelic and genotypic frequencies of the GDM and control groups were compared. For individuals with various genotypes, the level of blood glucose, serum lipids, and body mass index (BMI) were also compared.
The frequencies of AA, AG and GG genotypes for the GDM group were 32.2%, 52.2% and 15.6%, respectively, and 41.2%, 43.9% and 15.0%, for the control group, respectively. No significant difference was detected in the distribution of above genotypes between the two groups (chi-square=3.601, P=0.165). The frequencies of alleles A and G were 58.3% and 41.7% in the GDM group, and 63.1% and 36.9% in the control group, respectively. No significant difference was detected between the two groups too (chi
Dynamical downscaling generally performs poorly on the Tibetan Plateau (TP), due to the region’s complex topography and several aspects of model physics, especially convection and land surface ...processes. This study investigated the effects of the cumulus parameterization scheme (CPS) and land-surface hydrology scheme (LSHS) on TP climate simulation during the wet season using the RegCM4 regional climate model. To address these issues and seek an optimal simulation, we conducted four experiments at a 20 km resolution using various combinations of two CPSs (Grell and MIT-Emanuel), two LSHSs (the default TOPMODEL TOP, and Variable Infiltration Capacity VIC). The simulations in terms of 2-m air temperature, precipitation (including large-scale precipitation LSP and convective precipitation CP), surface energy-water balance, as well as atmospheric moisture flux transport and vertical motion were compared with surface and satellite-based observations as well as the ERA5 reanalysis dataset for the period 2006–2016. The results revealed that the model using the Grell and TOP schemes better reproduced air temperature but with a warm bias, part of which could be significantly decreased by the MIT scheme. All schemes simulated a reasonable spatial distribution of precipitation, with the best performance in the experiment using the MIT and VIC schemes. Excessive precipitation was produced by the Grell scheme, mainly due to overestimated LSP, while the MIT scheme largely reduced the overestimation, and the simulated contribution of CP to total precipitation was in close agreement with the ERA5 data. The RegCM4 model satisfactorily captured diurnal cycles of precipitation amount and frequency, although there remained some differences in phase and magnitude, which were mainly caused by the CPSs. Relative to the Grell scheme, the MIT scheme yielded a weaker surface heating by reducing net radiation fluxes and the Bowen ratio. Consequently, anomalous moisture flux transport was substantially reduced over the southeastern TP, leading to a decrease in precipitation. The VIC scheme could also help decrease the wet bias by reducing surface heating. Further analysis indicated that the high CP in the MIT simulations could be attributed to destabilization in the low and mid-troposphere, while the VIC scheme tended to inhibit shallow convection, thereby decreasing CP. This study’s results also suggest that CPS interacts with LSHS to affect the simulated climate over the TP.
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