Effectiveness of health management team program to enhance prevention of mother-to-child transmission of hepatitis B virus in Ningxia, China.

BACKGROUND: Hepatitis B mother-to-child transmission interruption (PMTCT) poses a formidable challenge in underdeveloped regions of China. This study aims to evaluate the effectiveness of PMTCT and the health management team (HMT) model in Ningxia, China, as well as the risk factors for adverse outcomes. METHODS: The PMTCT + HMT model was established, and 360 pregnant women diagnosed with HBV infection in 2020-2022 were selected and divided into the control and the study groups based on different intervention modes. HBV serum markers and HBV DNA levels were assessed, the indicators of compliance behaviors and adverse outcomes were compared, and the factors influencing adverse outcomes were analyzed. RESULTS: The majority of subjects were residents of the local city, married, with secondary school or higher education, and employees of public sectors. The proportion of ethnic minorities was 40.8% and 34.2% in the control group and study group. HBeAg positivity was 23.3% and 26.3%, and the proportion with HBV DNA levels ≥ 2 × 105 IU/mL was 9.2% and 7.1%. Compared with the control group (PMTCT alone), the PMTCT + HMT model led to improved maternal knowledge (17.5% vs. 57.1%), voluntary counseling (34.2% vs. 63.3%), and testing (37.5% vs. 70.4%). The incidence of adverse pregnancy outcomes ((including miscarriage, preterm birth) decreased significantly (17.5% vs. 6.2%), as did adverse neonatal outcomes (low birth weight and congenital HBV) (26.9% vs. 10.5%). Adverse outcomes were associated with low educational attainment, non-locals, unmarried status, and ethnic minority identity. Additionally, HBeAg positivity and HBV DNA levels ≥ 2 × 105 IU/mL were risk factors for adverse outcomes. CONCLUSIONS: The PMTCT + HMT model demonstrates significant effectiveness in preventing mother-to-child transmission of hepatitis B in Ningxia. The unique demographic structure of Ningxia region is closely linked to poor outcomes, emphasizing the importance of monitoring HBeAg status and HBV DNA viral load level.

FoxP3-miR-150-5p/3p suppresses ovarian tumorigenesis via an IGF1R/IRS1 pathway feedback loop.

Ovarian cancer (OC) causes more deaths than any other gynecological cancer. Many cellular pathways have been elucidated to be associated with OC development and progression. Specifically, the insulin-like growth factor 1 receptor/insulin receptor substrate 1 (IGF1R/IRS1) pathway participates in OC development. Moreover, accumulating evidence has shown that microRNA deregulation contributes to tumor initiation and progression. Here, our study aimed to investigate the molecular functions and regulatory mechanisms of miR-150, specifically, in OC. We found that the expression of miR-150-5p/3p and their precursor, mir-150, was downregulated in OC tissues; lower mir-150 levels were associated with poor OC patient outcomes. Ectopic mir-150 expression inhibited OC cell growth and metastasis in vitro and in vivo. Furthermore, both IRS1 and IGF1R were confirmed as direct targets of miR-150-5p/3p, and the miR-150-IGF1R/IRS1 axis exerted antitumor effects via the PI3K/AKT/mTOR pathway. Forkhead box protein 3 (FoxP3) positively regulated the expression of miR-150-5p/3p by binding to the mir-150 promoter. In turn, the PI3K/AKT/mTOR pathway downregulated FoxP3 and miR-150-5p/3p. Taken together, these findings indicate that a complex FoxP3-miR-150-IGF1R/IRS1-PI3K/AKT/mTOR feedback loop regulates OC pathogenesis, providing a novel mechanism for miR-150 as a tumor suppressor miRNA in OC.

BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA.

Cancer immune surveillance is an important host protection process that inhibits carcinogenesis and maintains cellular homeostasis. The major histocompatibility complex class I-related molecules A and B (MICA and MICB) are NKG2D ligands that play important roles in tumor immune surveillance. In the present study, by a combined bioinformatics prediction and experimental approach, we identify BCL11B 3'-UTR as a putative MICA and MICB ceRNA. We demonstrate in several human cell lines of different origins that the knockdown of BCL11B downregulates surface expression of MICA and MICB. Furthermore, we demonstrate miRNA dependency of BCL11B-mediated MICA and MICB regulation in Dicer knockdown HCT116 cells. In addition, MICA/B-targeting miRNAs (miR-17, miR-93, miR-20a, miR-20b, miR-106a, and miR-106b) repressed the expression of BCL11B by targeting its 3'-UTR. Moreover, we showed that the BCL11B knockdown-mediated downregulation of MICA/B resulted in reduced NK cell elimination in vitro and in vivo through reduced recognition of NKG2D. Of particular significance, BCL11B displays tumor-suppressive properties. The expression of BCL11B is downregulated in colon cancer tissues and associated with a reduced median survival of colon cancer patients. Taken together, our study revealed a new mechanism of BCL11B that prevents immune evasion of cancerous cells by upregulation of the NKG2D ligands MICA and MICB in a ceRNA manner.

miR-340-FHL2 axis inhibits cell growth and metastasis in ovarian cancer.

Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression in normal ovarian epithelium and endometrium, and treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) or trichostatin A (TSA) increased miR-340 expression in OC cells. In addition, ectopic miR-340 expression inhibited OC cell growth and metastasis in vitro and in vivo. Four and a half LIM domains protein 2 (FHL2) was confirmed as a direct target of miR-340 and silencing FHL2 mimicked the effects of miR-340 in OC cells. Further mechanistic study showed that miR-340 inhibited the Wnt/ß-catenin pathway by targeting FHL2, as well as downstream cell cycle and epithelial-to-mesenchymal transition (EMT) signals in OC cells. Moreover, the greatest association between miR-340 and FHL2 was found in 481 ovarian serous cystadenocarcinoma tissues via pan-cancer analysis. Finally, we revealed that lower miR-340 or higher FHL2 was associated with poor OC patient outcomes. Our findings indicate that the miR-340-FHL2 axis regulates Wnt/ß-catenin signaling and is involved in tumorigenesis in OC. Therefore, manipulating the expression of miR-340 or its target genes is a potential strategy in OC therapy.

VarCards: an integrated genetic and clinical database for coding variants in the human genome.

A growing number of genomic tools and databases were developed to facilitate the interpretation of genomic variants, particularly in coding regions. However, these tools are separately available in different online websites or databases, making it challenging for general clinicians, geneticists and biologists to obtain the first-hand information regarding some particular variants and genes of interest. Starting with coding regions and splice sties, we artificially generated all possible single nucleotide variants (n = 110 154 363) and cataloged all reported insertion and deletions (n = 1 223 370). We then annotated these variants with respect to functional consequences from more than 60 genomic data sources to develop a database, named VarCards (http://varcards.biols.ac.cn/), by which users can conveniently search, browse and annotate the variant- and gene-level implications of given variants, including the following information: (i) functional effects; (ii) functional consequences through different in silico algorithms; (iii) allele frequencies in different populations; (iv) disease- and phenotype-related knowledge; (v) general meaningful gene-level information; and (vi) drug-gene interactions. As a case study, we successfully employed VarCards in interpretation of de novo mutations in autism spectrum disorders. In conclusion, VarCards provides an intuitive interface of necessary information for researchers to prioritize candidate variations and genes.

Acetylation of hMOF Modulates H4K16ac to Regulate DNA Repair Genes in Response to Oxidative Stress.

Oxidative stress is considered to be a key risk state for a variety of human diseases. In response to oxidative stress, the regulation of transcriptional expression of DNA repair genes would be important to DNA repair and genomic stability. However, the overall pattern of transcriptional expression of DNA repair genes and the underlying molecular response mechanism to oxidative stress remain unclear. Here, by employing colorectal cancer cell lines following exposure to hydrogen peroxide, we generated expression profiles of DNA repair genes via RNA-seq and identified gene subsets that are induced or repressed following oxidative stress exposure. RRBS-seq analyses further indicated that transcriptional regulation of most of the DNA repair genes that were induced or repressed is independent of their DNA methylation status. Our analyses also indicate that hydrogen peroxide induces deacetylase SIRT1 which decreases chromatin affinity and the activity of histone acetyltransferase hMOF toward H4K16ac and results in decreased transcriptional expression of DNA repair genes. Taken together, our findings provide a potential mechanism by which oxidative stress suppresses DNA repair genes which is independent of the DNA methylation status of their promoters.

Significance of combined detection of JAK2V617F, MPL and CALR gene mutations in patients with essential thrombocythemia.

The aim of this study was to analyze the mutation rate of JAK2V617F, MPLW515L/K and CALR genes in adult patients with essential thrombocythemia (ET) and the accuracy of the combined detection by the receiver operating curve. Three hundred and forty-two cases with high-platelets (≥300×109/l) were consecutively selected. The patients were analyzed for routine blood examination, bone marrow biopsy and genetic testing. One hundred and fifty-four cases (45.03%) were diagnosed with ET and 188 cases of secondary thrombocythemia according to the hematopoietic and lymphoid tissue tumor classification standards of 2008. It was found that the mutant type of three genes showed three bands, whereas only one band for wild-type. The JAK2V617F and MPL mutations did not cause a change in the open reading frame and the CALR mutation resulted in its change. The mutation rate of JAK2V617F and CALR in ET group was significantly higher than that in the secondary thrombocythemia group (p<0.05). The positive mutation rate of MPL was only 4.55%. JAK2V617F-positive mutation alone was used to diagnose with ET. The area under the curve (AUC) was 0.721. The sensitivity was 72.4%, the specificity was 79.5% and the cut-off value was 0.25. When CALR-positive mutation alone was used to diagnose ET, the AUC, sensitivity, specificity and cut-off value were 0.664, 68.4, 82.4 and 0.09%, respectively. JAK2V617F combined with CALR mutation were used for diagnosis of ET. The AUC was 0.862, the sensitivity was 85.9%, the specificity was 87.8%, and the cut-off values were 0.21 and 0.07. In conclusion, the positive mutation rate of JAK2V617F and CALR in ET was higher, and the sensitivity, specificity and accuracy of the diagnosis of ET were significantly improved using the detection of JAK2V617F and CALR.

mirDNMR: a gene-centered database of background de novo mutation rates in human.

De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required. Therefore, in this study, we developed a novel database named mirDNMR for the collection of gene-centered background DNMRs obtained from different methods and population variation data. The database has the following functions: (i) browse and search the background DNMRs of each gene predicted by four different methods, including GC content (DNMR-GC), sequence context (DNMR-SC), multiple factors (DNMR-MF) and local DNA methylation level (DNMR-DM); (ii) search variant frequencies in publicly available databases, including ExAC, ESP6500, UK10K, 1000G and dbSNP and (iii) investigate the DNM burden to prioritize candidate genes based on the four background DNMRs using three statistical methods (TADA, Binomial and Poisson test). As a case study, we successfully employed our database in candidate gene prioritization for a sporadic complex disease: intellectual disability. In conclusion, mirDNMR (https://www.wzgenomics.cn/mirdnmr/) can be widely used to identify the genetic basis of sporadic genetic diseases.

Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population.

Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10⁻³, stage 2 validation; P = 3.00 × 10⁻³, P = 1.19 × 10⁻8 and P = 4.00 × 10⁻³ in three independent stage 3 replication populations; P = 4.87 × 10⁻¹², odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population.

Minor allele C of chromosome 1p32 single nucleotide polymorphism rs11206510 confers risk of ischemic stroke in the Chinese Han population.

BACKGROUND AND PURPOSE: Genome-wide association studies found that the common allele T of single nucleotide polymorphism rs11206510 on chromosome 1p32 was associated with increased low-density lipoprotein-cholesterol levels (LDL-C) and with risk of coronary artery disease (CAD) in white populations. The goals of this study are to determine whether rs11206510 is associated with LDL-C and CAD in a different ethnic population, namely a Chinese cohort, and to investigate whether rs11206510 is associated with ischemic stroke. METHODS: The association of rs11206510 with LDL-C was analyzed in 1415 Chinese Han subjects. The CAD study utilized a GeneID cohort with 1543 CAD patients and 1240 controls. For stroke studies, 2 independent cohorts were used and included the GeneID North cohort, with 1205 cases and 1205 controls, and the GeneID Central cohort, with 692 cases and 882 controls. RESULTS: Different from white populations, the minor allele C of rs11206510 was associated with increased LDL-C levels in the Chinese Han population (adjusted P=0.002) and conferred risk of early-onset CAD (380 cases vs 1240 controls; adjusted P=0.002, odds ratio, 1.89), but not with overall CAD (adjusted P=0.82). The allelic association with ischemic stroke was highly significant in 2 independent cohorts, with adjusted P=1.13x10(-5) (odds ratio,1.71) in the GeneID North cohort and adjusted P=9.32x10(-5) (odds ratio, 1.70) in the GeneID Central cohort. Genotypic association was also significant for both early-onset CAD and ischemic stroke. CONCLUSIONS: Our results indicate that single nucleotide polymorphism rs11206510 is associated with LDL-C levels and early-onset CAD in the Chinese Han population. For the first time to our knowledge, this study also demonstrates that rs11206510 confers a significant risk of ischemic stroke.

[Characterization of severe acute occupational poisoning accidents related to asphyxiating gases in China between 1989 and 2003].

OBJECTIVE: To analyze severe acute occupational poisoning accidents related to asphyxiating gases reported in China between 1989 and 2003, and to study the characteristics of severe acute occupational poisoning accidents and provide scientific evidences for prevention and control strategies. METHODS: The data from the national occupational poisoning case reporting system were analyzed with descriptive methods. RESULTS: (1) There were 273 severe acute occupational poisoning accidents related to asphyxiating gases for 15 years with 1638 workers poisoned and 600 workers died, which accounted for 53.95% in total accidents and 35.17% of workers poisoned and 78.64% of workers died of all severe acute occupational poisoning accidents. The average poisoning age was (33.8 +/- 9.7) years old and the average death age was (36.6 +/- 10.0) years old. (2) Most of the accidents were caused by hydrogen sulfide, carbon monoxide and carbon dioxide respectively, and mainly occurred in chemical industry, mining, water disposal industry, paper making industry and brewing industry. The risk was higher in some jobs than others, such as cleanout, machine maintenance and repair, production, mine and digging. The poisoning accidents occurred more frequently from April to September each year and occurred in the confined space, in the basement and the mine, and workers died of poisoning mostly were men. CONCLUSION: (1) The severe acute occupational poisoning accidents related to asphyxiating gases are more dangerous than others. (2) The control of poisoning accidents related to hydrogen sulfide, carbon monoxide and carbon dioxide, which occurred easily in the confined space, should be paid more attention to, and good work practice should be developed on some posts, such as digging, cleanout, dredge, machine maintenance and repair and mine.

[Characterization of severe acute occupational poisoning accidents related to irritating gases in China between 1989 and 2003].

OBJECTIVE: To analyze severe acute occupational poisoning accidents related to irritating gases reported in China between 1989 and 2003, and to study the characteristics of severe acute occupational poisoning accidents and provide scientific evidences for prevention and control strategies. METHODS: The data from the national occupational poisoning case reporting system were analyzed with descriptive methods. RESULTS: (1) There were 92 severe acute occupational poisoning accidents related to asphyxiating gases during 15 years, which showed that there were 14.5 accidents occurred each year. Forty types of chemicals were reported to cause poisoning accidents directly. On average, there were 14.5 persons poisoned and 0.8 persons died of poisoning in each event. The number of death of poisoning reached 7 in most of the severe accidents. Chlorine was the main irritating gas resulting in poisoning accidents according to the number of accidents, cases and death. CONCLUSION: (1) The severe acute occupational poisoning related to irritating gases are more dangerous than others because of it is involved in more cases in each accident. (2) The accidents have concentricity in the certain types of chemicals, industries and jobs, and should be focused on control. (3) It is important to develop the program about early warning and forecast and the first aid.