Novel T cell exhaustion gene signature to predict prognosis and immunotherapy response in thyroid carcinoma from integrated RNA-sequencing analysis.

Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell-cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients.

Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis.

BACKGROUND: Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes. OBJECTIVE: To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM). METHODS: We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia. RESULTS: For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05). CONCLUSION: The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.

Circular RNA EIF3I promotes papillary thyroid cancer progression by interacting with AUF1 to increase Cyclin D1 production.

Circular RNAs (circRNAs) play an important role in regulating the development of human cancers through diverse biological functions. However, the exact molecular mechanisms underlying the role of circRNAs in papillary thyroid cancer (PTC) remain largely unknown. Here, we found that hsa_circ_0011385, designated as circular eukaryotic translation initiation factor 3 subunit I (circEIF3I), preferentially localized in the cytoplasm of PTC cells and was more stable than its linear counterpart, EIF3I. Gain- and loss-of-function studies indicated that circEIF3I promoted PTC progression by facilitating cell proliferation, cell cycle, cell migration, and invasion in vitro, as well as PTC cell proliferation in vivo. Mechanistically, circEIF3I interacted with AU-rich element (ARE) RNA-binding factor 1 (AUF1) in the cytoplasm of PTC cells, thus reducing the degradation of Cyclin D1 mRNA and increasing Cyclin D1 protein production, ultimately resulting in PTC progression. Collectively, our results demonstrate the vital role of circEIF3I in PTC progression, supporting its significance as a potential therapeutic target.

Association of sleep behaviors, insulin resistance surrogates, and the risk of hypertension in Chinese adults with type 2 diabetes mellitus.

Objective: Our aim was to evaluate the association between midday napping, combined sleep quality, and insulin resistance surrogates and the risk of hypertension in patients with type 2 diabetes mellitus (T2DM). Methods: Data were collected using a standardized questionnaire. Binary logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension. Systolic and diastolic blood pressure were grouped as categorical variables and unpaired two-sided Student's t-test and Spearman correlation analysis were performed to estimate the association between different blood pressure levels and insulin resistance surrogates. Results: The overall prevalence rate of hypertension was 50%. Age (OR = 1.056, 95% CI:1.044-1.068), poor sleep quality (OR = 1.959, 95% CI:1.393-2.755), hyperlipidemia (OR = 1.821, 95% CI:1.462-2.369), family history of hypertension (OR = 2.811, 95% CI:2.261-3.495), and obesity (OR = 5.515, 95% CI:1.384-21.971) were significantly associated with an increased risk of hypertension. Midday napping for 1-30 min was negatively correlated with the risk of hypertension (OR = 0.534, 95% CI:0.305-0.936, P <0.05). Conclusion: Poor sleep quality and obesity are independent risk factors for hypertension. Midday napping (1-30 min) is associated with a decreased risk of hypertension in patients with T2DM.

Increased serum IL-12 levels are associated with adverse IVF outcomes.

Interleukin-12 (IL-12) is involved in the occurrence and development of many diseases, such as preeclampsia, intrauterine growth restriction, preterm labor, and recurrent pregnancy losses. This study aimed to determine whether a high serum level of IL-12 was associated with adverse in vitro fertilization (IVF) outcomes. Included infertile women with high serum IL-12 levels who underwent IVF cycles and infertile controls with pure tubal etiology. The impact of serum IL-12 on baseline and clinical characteristics, immune-related indicators, IVF laboratory, and pregnancy outcomes were compared. In addition, the correlation of follicular fluid IL-12 and serum IL-12 level and the role of IL-12 in apoptosis of granulosa cells (GCs) was investigated. Women with high serum IL-12 levels had lower numbers of retrieved oocytes, embryos, perfect and available embryos, lower rates of perfect and available embryos, and blastocyst formation. Additionally, significantly higher levels of serum Th1, Th2, and Th17-related cytokines were observed in women with high serum IL-12 levels than in the controls. Meanwhile, the follicular fluid IL-12 levels were positively correlated with serum IL-12 levels, and IL-12 promoted apoptosis of GCs in vitro. We concluded that women with serum high IL-12 levels may have adverse IVF outcomes, partly by promoting apoptosis of GCs. Therefore, early screening for cytokines, especially IL-12, and appropriate consultation for couples receiving IVF-ET should be considered. In addition, specific immune and inflammatory mechanisms associated with high serum IL-12 levels should be further explored.

Regional variation of polybrominated diphenyl ethers in East Asian finless porpoises in the East China Sea.

Certain polybrominated diphenyl ethers (PBDEs) have been banned for years, however, they still possess the potential to harm marine cetaceans. In this study, 56 East Asian finless porpoises (EAFPs) collected from three locations of the East China Sea between 2009 and 2011, were analyzed to determine the presence of typical PBDE congeners. Among all the samples, BDE47 was the main congener, constituting ∼48.3 % of the ΣPBDEs. Significant variations (p < 0.01) in PBDE abundance were observed among different regions (Pingtan: 172.8 ng/g, Lvsi: 61.2 ng/g and Ningbo: 32.9 ng/g). In addition, there was a significant positive correlation between PBDE abundance and male body length. The general ΣPBDEs concentration of this population was lower compared to other populations and cetaceans. Although combined risk assessments indicated a low risk to porpoise health, long-term surveillance is essential as PBDEs are not completely banned.

The Correlation Between Health Risk Factors and Diabesity and Lipid Profile Indicators: The Role Mediator of TSH.

Introduction: Obesity in adults is a problem, particularly when paired with other metabolic abnormalities. Previous research have linked various screening approaches to diabetes, but additional evidence points to the relevance of combining diabetes screening methods with obesity and its effects. This research examined the impact of thyroid hormones (TSHs) and health risk factors (HRFs) in screening for obesity and diabetes in Chinese populations, and whether age can modulate this association. Methods: From March to July 2022, the Hefei Community Health Service Center connected with the First Affiliated Hospital of Anhui Medical University was chosen, and the multi-stage cluster sample approach was utilized to test adults aged 21-90 in each community. Latent category analysis (LCA) was performed to investigate the clustering patterns of HRFs. A one-way ANOVA was used to examine waist circumference (WC), biochemical markers, and general data. Furthermore, multivariate logistic regression analysis was utilized to investigate the relationship between health risk variables and WC. Results: A total of 750 individuals without a history of major problems who had a community health physical examination were chosen, with missing data greater than 5% excluded. Finally, 708 samples were included in the study with an effective rate of 94.4%. The average WC was (90.0±10.33) cm, the prevalence in the >P75, P50~P75, P25~P50, and ≤P25 groups were 24.7%, 18.9%, 28.7% and 27.7%, respectively. The average TSH was (2.76±2.0) µIU/mL. Male (ß=1.91), HOMA-IR (ß=0.06), TyG (ß=2.41), SBP (ß=0.08), TG (ß=0.94) and UA (ß=0.03) were more likely to have a higher prevalence of WC level. The analyses revealed significant correlations between HRFs, TSH, age, other metabolic indexes and WC (P < 0.05). Discussion: Our findings suggest that the quality of metabolic-related indicators used to successfully decrease diabetes in Chinese individuals with high HRFs levels should be prioritized. Comprehensive indicators might be a useful and practical way for measuring the metabolic evolution of diabetes level levels.

Anti-Ro/SSA and/or anti-La/SSB antibodies are associated with adverse endometrial status.

PROBLEM: Anti-Ro/SSA and/or anti-La/SSB (anti-SSA/SSB) antibodies impair pregnancy outcomes, including embryo implantation and pregnancy maintenance. Optimal endometrial immune status is essential for successful pregnancy. However, whether these antibodies affect endometrial immune status is still unclear. Menstrual blood can be collected non-invasively, differs from peripheral blood, and can reflect the endometrial immune status. We herein focused on changes in subsets of natural killer (NK) cells and T cells in menstrual blood. METHODS OF STUDY: Menstrual blood samples from anti-SSA/SSB antibody-positive (n = 18) and anti-SSA/SSB antibody-negative control (n = 8) women were collected, and the profile of lymphocyte subsets was analyzed. The phenotypes of menstrual blood CD49a- and CD49a+ NK cells were compared, and the abundance of NK and CD49a+ NK cells in menstrual blood of the two groups was assessed. Additionally, CD4+T and CD8+T cells were investigated for their ability to secret functional cytokines. RESULTS: Menstrual blood contains a large number of (mostly CD49a+) NK cells, which exhibited a more exhausted phenotype with greater expression of the immune checkpoint molecules programmed cell death protein 1 and Tim-3 compared to CD49a- conventional NK cells. CD8+T cells in menstrual blood from anti-SSA/SSB antibody-positive women produced a stronger response after stimulation, accompanied by increased interferon-γ, tumor necrosis factor-α, and granzyme B secretion (P < 0.05, separately). CONCLUSION: Menstrual blood cell composition differs between anti-SSA/SSB antibody-positive women and normal controls, especially in terms of CD49a+ NK cells and CD8+T cells, unbalancing the immune cell composition and inflammatory uterine microenvironment and possibly contributing to adverse pregnancy outcomes.

Anticardiolipin and/or anti-ß2-glycoprotein-I antibodies are associated with adverse IVF outcomes.

Objective: The purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-ß2-glycoprotein-I (aß2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes. Materials and methods: The study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed. Results: A total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls. Conclusion: Women with aPL such as aCL and/or aß2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET.

Objective: To investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: 75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and >10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed. Results: (1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P<0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P<0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P<0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P<0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P<0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality. Conclusion: Weight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR1800018298.

Novel mutations in NLRP5 and PATL2 cause female infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest.

PURPOSE: This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. METHODS: Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5. RESULTS: A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively. CONCLUSIONS: This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.

Anti-Ro/SSA and/or anti-La/SSB antibodies are associated with adverse IVF and pregnancy outcomes.

Anti-Ro/SSA and/or anti-La/SSB antibodies (anti-SSA/SSB) were reported to increase the risk of recurrent pregnancy loss. However, the effects of anti-SSA/SSB antibodies on in-vitro fertilization (IVF) and pregnancy outcomes were still unclear. The purpose of the study was to determine whether anti-SSA/SSB antibodies were detrimental to IVF and pregnancy outcomes. This study included 55 anti-SSA/SSB antibodies-positive women and 61 anti-SSA/SSB antibodies-negative control women receiving gonadotropin-releasing hormone (GnRH) agonist long protocol (n = 30 and 39, respectively) or GnRH antagonist protocol (n = 25 and 22, respectively) for in-vitro fertilization and embryo transfer (IVF-ET). The impact of anti-SSA/SSB antibodies on immune-related indicators, fertilization, embryo development and pregnancy outcomes were analyzed. With either GnRH agonist or antagonist protocol, women with anti-SSA/SSB had higher levels of peripheral blood cytokines, including TNF-α and IL-17A, lower levels of peripheral blood Th and NK cells, and poor IVF outcomes, including lower number of retrieved oocytes and embryos, lower M II oocytes rate, blastocyst formation rate, and perfect and available embryo rates. Moreover, clinical pregnancy rate, implantation rate, take-home baby rate, and birth weight were significantly lower in the study group as compared with those of the control group. In conclusion, women with anti-SSA/SSB are associated with adverse IVF and pregnancy outcomes. Screening for these antibodies and proper counselling of couples undergoing IVF-ET should be considered. Underlying immunopathology associated with SSA/SSB antibodies and reproduction should be explored further.

Novel Mutations in CDC20 Are Associated with Female Infertility Due to Oocyte Maturation Abnormality and Early Embryonic Arrest.

The cell division cycle 20 (CDC20) protein is a co-activator of anaphase-promoting complex/cyclosome (APC/C), required for mitotic exit and also meiotic exit, containing seven WD40 repeats in the C-terminus responsible for protein-protein interactions. Recently, a previous study has shown that biallelic mutations in CDC20 are causative for female infertility with abnormalities in oocyte maturation and embryonic development. This study is to further identify new mutations of CDC20 and the prevalence of variants in our cohort. A cohort of 50 primary infertile females with oocyte maturation abnormality and early embryonic arrest were recruited. Genomic DNA was isolated from peripheral blood samples. Mutation screening of all the coding regions of CDC20 was performed by Sanger sequencing. The pathogenicity of the identified variants on the CDC20 protein was accessed in silico. Two CDC20 variants, a nonsense mutation p.R262* and a missense mutation p.A211T, identified in one female of 50 unrelated affected individuals, accounting for a relative small proportion of this cohort (2%). In silico analysis revealed that the p.R262* would cause no production of protein or a truncated protein lacking five WD40 repeats in the C-terminus; and that p.A211T may interfere with the formation of a deep hydrophobic pocket and thus disturb the binding of CDC20 protein to the substrates of APC/C. This study identified two novel mutations in CDC20, further expanding the mutation spectrum of this gene. Our findings further confirm that biallelic mutations in CDC20 occur in a proportion of infertile females with oocyte maturation abnormality and early embryonic arrest.

Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss.

Maintaining homeostasis of the decidual immune microenvironment at the maternal-fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.

A Simple and Efficient Method to Cryopreserve Human Ejaculated and Testicular Spermatozoa in -80°C Freezer.

Human autologous sperm freezing involves ejaculated sperm, and testicular or epididymal puncture sperm freezing, and autologous sperm freezing is widely used in assisted reproductive technology. In previous studies, researchers have tried to cryopreserve sperm from mammals (rats, dogs, etc.) using a -80°C freezer and have achieved success. It is common to use liquid nitrogen vapor rapid freezing to cryopreserve human autologous sperm. However, the operation of this cooling method is complicated, and the temperature drop is unstable. In this study, we compared the quality of human ejaculation and testicular sperm after liquid nitrogen vapor rapid freezing and -80°C freezing for the first time. By analyzing sperm quality parameters of 93 ejaculated sperm and 10 testicular sperm after liquid nitrogen vapor rapid freezing and -80°C freezing, we found reactive oxygen species (ROS) of sperm of the -80°C freezer was significantly lower than liquid nitrogen vapor rapid freezing. Regression analysis showed that progressive motility, ROS, and DNA fragmentation index (DFI) in post-thaw spermatozoa were correlated with sperm progressive motility, ROS, and DFI before freezing. For the freezing method, the -80°C freezer was positively correlated with the sperm progressive motility. Among the factors of freezing time, long-term freezing was negatively correlated with sperm progressive motility and ROS. Although freezing directly at -80°C freezer had a slower temperature drop than liquid nitrogen vapor rapid freezing over the same period, the curves of the temperature drop were similar, and slight differences in the freezing point were observed. Furthermore, there were no statistically significant differences between the two methods for freezing testicular sperm. The method of direct -80°C freezing could be considered a simplified alternative to vapor freezing for short-term human sperm storage. It could be used for cryopreservation of autologous sperm (especially testicular sperm) by in vitro fertilization centers. Clinical Trial Registration: (website), identifier (ChiCTR2100050190).

Association of two polymorphisms of miRNA-146a rs2910164 (G > C) and miRNA-499 rs3746444 (T > C) with asthma: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis to determine the association between two single nucleotide polymorphisms (SNPs) miRNA146a rs2910164 (G > C) and miRNA-499 rs3746444 (T > C) and asthma risk. DATA SOURCES: PubMed and Embase (updated May 17, 2019). KEYWORDS: (microRNA OR microRNAs) AND (polymorphism OR polymorphisms) AND (Asthmas OR Bronchial Asthma OR Asthma, Bronchial). RESULTS: Six eligible case-control studies (2441 asthma cases and 3044 controls) met our inclusion criteria. A trend of increased asthma risk was indicated by the heterozygote model (miR-499: TC versus TT, OR = 1.38, 95% CI = 1.06-1.79, P < 0.01) and the dominant model (miR-499: TC + CC versus TT, OR = 1.60, 95% CI = 1.07-2.39, P < 0.01) of miRNA-499 rs3746444. Polymorphisms rs2910164 in miRNA-146a of the allele model (miR-146a: C versus G, OR = 0.84, 95% CI = 0.74-0.96, P = 0.238), homozygote model (miR-146a: CC versus GG, OR = 0.68, 95% CI = 0.51-0.91, P = 0.213), recessive model (miR-146a: CC versus GC + GG, OR = 0.75, 95% CI = 0.60-0.94, P = 0.149) indicated a decreased risk of asthma. CONCLUSIONS: The miR-499 rs3746444 (T > C) polymorphism is associated with asthma susceptibility and miRNA-146a rs2910164 (G > C) polymorphism has a protective role against susceptibility to asthma.

Elimination of Mother-to-Infant Transmission of Hepatitis B Virus: 35 Years of Experience.

Chronic hepatitis B viral (HBV) infection remains a major health threat, especially in high-prevalence areas. Most infants infected by mother-to-infant HBV transmission become chronic carriers. In Taiwan, many important preventive interventions have been implemented to block the perinatal transmission of HBV in the past 35 years. The first nationwide universal HBV vaccination program was launched in Taiwan in July 1984. The three-dose HBV vaccine completion rate reached 98.1% in 2018. The prevalence of Hepatitis B surface antigen (HBsAg) decreased from 9.8% in pre-vaccinated period in 1984 to 0.5% in the vaccinated cohort in 2014. The incidence of hepatocellular carcinoma in children aged 6-9 years significantly declined from 0.52 to 0.13 per 100,000 children born before and after 1984, respectively. Furthermore, we have performed a maternal HBV screening program during pregnancy since 1984, with the screening rate peaked at 93% in 2012. The HBsAg- and HBeAg-seropositive rate in pregnant women declined from 13.4% and 6.4% in 1984-1985 to 5.9% and 1.0% in 2016, respectively. To closely control perinatal HBV infection, we have administered hepatitis B immunoglobulin immediately after birth and checked the serum level of HBsAg and anti-HBs in high-risk babies born to HBsAg-seropositive mothers, irrespective of their HBeAg status, since July 2019. We have also adopted short-term antiviral treatments such as tenofovir 300 mg daily in the third trimester for highly viremic mothers and reduced the perinatal infection rates from 10.7 to 1.5%. Through all these efforts, we expect to meet the global goal of eliminating HBV infection by 2030.

Identification of microRNAs that Regulate the MAPK Pathway in Human Cumulus Cells from PCOS Women with Insulin Resistance.

Polycystic ovary syndrome (PCOS) is one of the most common gynaecological endocrine disorders, and more than 60% of PCOS patients have varying degrees of insulin resistance (IR). The regulatory role of microRNAs (miRNAs) at post-transcriptional levels in human cumulus cells relating to IR in PCOS remains unclear. In this case-control study, 26 PCOS patients with IR (PCOS-IR) and 24 patients without IR (PCOS-control) were enrolled. We determined the differentially expressed miRNA and mRNA using next-generation sequencing technology, and these miRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (PCR). These miRNA regulating pathways (e.g., MAPK pathway) were analysed by bioinformatics analysis, and the Rap1b was demonstrated to be targeted by miR-612 based on quantitative real-time PCR, western blot and luciferase activity assay. A total of 59 known miRNAs and 617 differentially expressed genes were identified that differentially expressed between PCOS-IR and PCOS-control cumulus cells. Moreover, the potential regulating roles of miRNAs and their targeting genes in pathophysiology of IR and PCOS were analysed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and several key processes were enriched, such as MAPK activity. Furthermore, Rap1b, a regulator of the MAPK pathway, was demonstrated to be suppressed directly by miR-612 in PCOS-IR cumulus cells based on negative expression correlation validation, dual luciferase activity assay and reduction of Rap1b expression after miR-612 mimics transfection. Our results suggested that miRNAs and their targeted pathways in ovarian cumulus cells may play important roles in the aetiology and pathophysiology of PCOS with IR.