Association of Toll-Like Receptor 3 Polymorphisms with Kaposi's Sarcoma-Associated Herpesvirus Infection Among Human Immunodeficiency Virus-Infected Individuals in Xinjiang, China.

Toll-like receptors (TLRs) play a crucial role in the innate immune response to pathogens, and TLR3 could recognize and control the herpesvirus. We studied the effect of TLR3 polymorphisms on the risk of Kaposi's sarcoma-associated herpesvirus (KSHV) infection. A cross-sectional study was performed among human immunodeficiency virus (HIV)-infected individuals in Xinjiang, a KSHV-endemic region of China. The frequencies of nine single-nucleotide polymorphisms (SNPs) in TLR3 in 370 KSHV-infected patients and 558 controls, and their impact on plasma IFN-γ levels, were compared. The effect of TLR3 SNPs on the KSHV viral load in KSHV-infected subjects was also assessed. The minor allelic variant at rs13126816 was more common among KSHV-seronegative than KSHV-infected individuals. Two TLR3 SNPs (rs13126816 and rs3775291) showed a protective effect against KSHV infection (rs13126816: odds ratio [OR]dominant = 0.66, 95% confidence interval [CI]: 0.50-0.87; ORoverdominant = 0.65, 95% CI: 0.49-0.87; rs3775291: ORdominant = 0.76, 95% CI: 0.58-0.99; ORoverdominant = 0.75, 95% CI: 0.57-0.98). These associations were stronger in the Uyghur compared with the Han population. The haplotype, CGAC, significantly correlated with the risk of KSHV infection (OR = 0.72, p = 0.029). KSHV-infected individuals with homozygous rs13126816 AA genotypes had a lower KSHV viral load (aOR = 0.14; p = 0.038). However, no association was observed between TLR3 SNPs and plasma levels of IFN-γ. Genetic variants in TLR3 reduce the risk of KSHV infection and affect KSHV reactivation among HIV-infected individuals, especially in the Uyghur population.

Association between prior appendectomy and the risk and course of Crohn's disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The appendix has an important immune function in both health and disease, and appendectomy may influence microbial ecology and immune function. This meta-analysis aims to assess the association between appendectomy and the risk and course of Crohn's disease (CD). METHODS: PubMed, EMBASE, and the Cochrane Library were used to identify all studies published until June 2022. Data from studies evaluating the association between appendectomy and CD were reviewed. RESULTS: A total of 28 studies were included in the final analysis, comprising 22 case-control and 6 cohort studies. A positive relationship between prior appendectomy and the risk of developing CD was observed in both case-control studies (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.22-2.08) and cohort studies (relative risk [RR]: 2.28, 95% CI: 1.66-3.14). The elevated risk of CD persisted 5 years post-appendectomy (RR = 1.24, 95% CI: 1.12-1.36). The risk of developing CD was similarly elevated regardless of the presence (RR = 1.64, 95% CI: 1.17-2.31) or absence (RR = 2.77, 95% CI: 1.84-4.16) of appendicitis in patients. Moreover, significant differences were found in the proportion of terminal ileum lesions (OR = 1.63; 95% CI: 1.38-1.93) and colon lesions (OR = 0.70; 95% CI: 0.5-0.84) between CD patients with appendectomy and those without appendectomy. CONCLUSIONS: The risk of developing CD following an appendectomy is significant and persists 5 years postoperatively. Moreover, the elevated risk of CD may mainly occur in the terminal ileum.

Evolutionary characteristics and immune mutation of hepatitis C virus genotype 1b among intravenous drug users in mainland, China.

China is one of the countries with the heaviest burden of hepatitis C virus (HCV) worldwide, especially subtype 1b. To better control hepatitis C, insights into the characteristics of dynamic spread and genomic mutations are urgently needed. We retrieved sequences of HCV-1b NS5B among intravenous drug users (IDUs) and general people (Non-IDUs) in China from 2000 to 2011 in NCBI. Bayesian phylogenetic and phylogeographic analyses were used to evaluate the transmission dynamics of HCV-1b. Non-synonymous substitutions were detected to illustrate immune adaptation. Evolutionary history demonstrated that HCV-1b effective population size experienced a sharp increase in 1990. HCV-1b sequences among IDUs had a higher estimated evolutionary rate (5.7185 × 10-3  substitutions/site/year) than overall (7.7332 × 10-4 ). 105/136 (77.2%) of HCV-1b sequences clustered into 38 networks. The average non-synonymous HCV-1b immune epitopes among IDUs were 0.211, higher than non-IDUs, especially in the HLA-A*02 molecular recognition region. All of these posed significant challenges for the prevention and treatment of HCV. Heterogeneity and genetic linkages of HCV-1b suggest that evolutionary surveillance of HCV in cities in east-central China and among IDUs could not be neglected.

Environmental risk factors and genetic markers of Kaposi's sarcoma-associated herpesvirus infection among Uygur population in Xinjiang, China.

Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China. Determinants of KSHV seropositivity among high-risk groups are not well understood. We seek to identify genetic and environmental predisposing factors for KSHV infection among Uygurs in this endemic region. A cross-sectional study was performed among the Uygur population in Xinjiang, China. KSHV-antibodies were detected using immunofluorescence assay (IFA) and human leukocyte antigen (HLA) alleles were genotyped. Univariate and multivariate logistic regression analyses were applied to explore the environmental and genetic risk factors of KSHV seropositivity. Finally, a total of 721 participants were included. The seroprevalence of KSHV was 24.1% among this population. Sweet-food preference (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.03-3.34), and coronary heart disease (OR 1.91, 95%CI 1.24-2.94) were statistically correlated with KSHV infection. HLA-DQB1*06:09 were found to significantly increase the risk of KSHV infection under all 3 models (ORAllelic = 4.06; ORDominant = 3.27; and ORRecessive = 8.06). Six SNPs (SNP0260, SNP0361, SNP0797, SNP0852, SNP1159, and SNP1375) in the DQB1 and DRB1 region and haploid type GTCTAACTAATC in block 17 were statistically associated with KSHV infection. We demonstrated that genetic variations in HLA-DQB1/DRB1 and environmental risk factors were strongly associated with KSHV infection among this population.

Prevalence of transmitted HIV-1 drug resistance among treatment-naive individuals in China, 2000-2016.

Human immunodeficiency virus (HIV) with transmitted drug-resistance (TDR) limits the therapeutic options available for treatment-naive HIV patients. This study aimed to further our understanding of the prevalence and transmission characteristics of HIV with TDR for the application of first-line antiretroviral regimens. A total of 6578 HIV-1 protease/reverse-transcriptase sequences from treatment-naive individuals in China between 2000 and 2016 were obtained from the Los Alamos HIV Sequence Database and were analyzed for TDR. Transmission networks were constructed to determine genetic relationships. The spreading routes of large TDR clusters were identified using a Bayesian phylogeographic framework. TDR mutations were detected in 274 (4.51%) individuals, with 1.40% associated with resistance to nucleoside reverse transcriptase inhibitors, 1.52% to non-nucleoside reverse transcriptase inhibitors, and 1.87% to protease inhibitors. The most frequent mutation was M46L (58, 0.89%), followed by K103N (36, 0.55%), M46I (36, 0.55%), and M184V (26, 0.40%). The prevalence of total TDR initially decreased between 2000 and 2010 (OR = 0.83, 95% CI 0.73-0.95) and then increased thereafter (OR = 1.50, 95% CI 1.13-1.97). The proportion of sequences in a cluster (clustering rate) among HIV isolates with TDR sequences was lower than that of sequences without TDR (40.5% vs. 48.8%, P = 0.023) and increased from 27.3% in 2005-2006 to 63.6% in 2015-2016 (P < 0.001). While most TDR mutations were associated with reduced relative transmission fitness, mutation M46I was associated with higher relative transmission fitness than the wild-type strain. This study identified a low-level prevalence of TDR HIV in China during the last two decades. However, the increasing TDR HIV rate since 2010, the persistent circulation of drug resistance mutations, and the expansion of self-sustaining drug resistance reservoirs may compromise the efficacy of antiretroviral therapy programs.

Increasing prevalence of NAFLD/NASH among children, adolescents and young adults from 1990 to 2017: a population-based observational study.

OBJECTIVE: To describe the prevalence and variations of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) among children and adolescents (CADs) and young adults (YADs). DESIGN: A population-based observational study. SETTING: Annual cases and prevalence of NAFLD/NASH from 1990 to 2017, by sex, region and country were collected from the Global Burden of Disease database. MAIN OUTCOME MEASURES: The estimated annual percentage change, which was calculated by a regression line, was used to quantify the temporal trends in NAFLD/NASH burden among young people at the global, regional and national levels. RESULTS: Globally, NAFLD/NASH incidence increased from 19.34 million in 1990 to 29.49 million in 2017 among CADs, with an annual increase of 1.35%. Additionally, in YADs, the number of cases and NAFLD/NASH prevalence significantly increased during this period, independent of sex and region. The greatest NAFLD/NASH increase was in North Africa and the Middle East. Almost all countries showed an increasing trend from 1990 to 2017, with the most pronounced increase observed in the developed regions. CONCLUSIONS: The epidemiology of NAFLD/NASH in young people has changed considerably over the last three decades. Both the prevalence and number of cases have increased irrespective of sex, age and region. This phenomenon can result in a predictable increase in chronic liver disease burden in the near future. Understanding the prevalence of NAFLD/NASH and its variations is of paramount importance to develop strategies to implement public health policy.

Early prediction of mortality risk among patients with severe COVID-19, using machine learning.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, has been spreading globally. We aimed to develop a clinical model to predict the outcome of patients with severe COVID-19 infection early. METHODS: Demographic, clinical and first laboratory findings after admission of 183 patients with severe COVID-19 infection (115 survivors and 68 non-survivors from the Sino-French New City Branch of Tongji Hospital, Wuhan) were used to develop the predictive models. Machine learning approaches were used to select the features and predict the patients' outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models' performance. A total of 64 with severe COVID-19 infection from the Optical Valley Branch of Tongji Hospital, Wuhan, were used to externally validate the final predictive model. RESULTS: The baseline characteristics and laboratory tests were significantly different between the survivors and non-survivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the external validation sets were 0.881. The sensitivity and specificity were 0.839 and 0.794 for the validation set, when using a probability of death of 50% as the cutoff. Risk score based on the selected variables can be used to assess the mortality risk. The predictive model is available at [https://phenomics.fudan.edu.cn/risk_scores/]. CONCLUSIONS: Age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level of COVID-19 patients at admission are informative for the patients' outcomes.

Evolutionary characteristics and genetic transmission patterns of predominant HIV-1 subtypes among men who have sex with men in China.

OBJECTIVES: Men who have sex with men (MSM) represent one of the major risk groups for HIV-1 infection in China, and the predominant subtypes among this population has changed over the last two decades. The objective of this study was to determine the evolutionary characteristics and transmission patterns of the dominant HIV-1 strains in the Chinese MSM population. METHODS: A total of 4980 published HIV-1 pol gene sequences from MSM in China were retrieved and comprehensive evolutionary and transmission analyses were then conducted. Bayesian coalescent-based methods and selection pressure analyses were used to reconstruct the time-scale and demographic history and to estimate other evolutionary parameters. Transmission patterns were characterized using network analyses. RESULTS: There were 2546 (51.12%) CRF01_AE, 1263 (25.36%) CRF07_BC, and 623 (12.51%) subtype B, accounting for 88.99% of the total sequences. From 2000 to 2016, the prevalence of CRF01_AE was stable, comprising nearly half of all sequences over time (58.33-45.38%, p=0.071). CRF07_BC increased slightly from 13.3% to 22.49% (p<0.001), while subtype B decreased dramatically from 41.67% to 9.04% (p<0.001). Demographic reconstruction showed that the greatest expansion of the HIV epidemic occurred between 1999 and 2005. CRF01_AE had a higher estimated evolutionary rate (2.97×10-3 substitutions/site/year) and exhibited more sites under positive selection (25/351 codons) compared to the other subtypes. Network analyses showed that CRF07_BC (68.29%, 84/123) had a higher proportion of cross-region networks than CRF01_AE (49.1%, 174/354) and subtype B (36.46%, 35/96) (p<0.001). CONCLUSIONS: The predominant subtypes of HIV-1 in Chinese MSM have different evolutionary characteristics and transmission patterns, which poses a significant challenge to HIV treatment and disease prevention.

Social behavioral correlates of Kaposi sarcoma-associated herpesvirus infection among Han and Uygur populations in Xinjiang, China.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China and its prevalence varies considerably across ethnic groups. The current study explored the prevalence and correlates of KSHV infection among Han and Uygur populations in Xinjiang. METHODS: A cross-sectional study, including 282 Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants underwent face to face questionnaire interview. Plasma samples were collected and screened for KSHV infection using immunofluorescence assay. Univariate and multivariate analyses were conducted to examine the correlates of KSHV seropositivity. RESULTS: The KSHV seroprevalence was 41.6% (95% confidence interval [CI], 37.6-45.6) overall and was higher in the Uygur group (59.9%; 95% CI, 54.3-65.4) than the Han group (21.3%; 95% CI, 16.6-26.5). A significant difference in the geometric mean titer (GMT) of the KSHV antibodies was detected between the Uygur and Han groups (158.2; interquartile range [IQR], 80-320 vs 89.1; IQR, 40-160; P < 0.001). After adjusting for potential confounders, Uygur ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05-8.90), age greater than or equal to 50 years (OR, 1.84; 95% CI, 1.24-2.77), and preference for meat diet (OR, 2.15; 95% CI, 1.05-4.46) were significantly associated with increased odds of KSHV seropositivity. CONCLUSION: The study demonstrated high prevalence and correlates of KSHV infection in both Han and Uygur populations in Xinjiang, China. There is an urgent need for programmatic adaptation to address primary prevention interventions of KSHV infection in this endemic region.