Novel genetic variants linked to prelabor rupture of membranes among Chinese pregnant women.

INTRODUCTION: The etiology of prelabor rupture of membranes (PROM), either preterm or term PROM (PPROM or TPROM), remains largely unknown. This study aimed to investigate the association between maternal genetic variants (GVs) and PROM and further establish a GV-based prediction model for PROM. METHODS: In this case-cohort study (n = 1166), Chinese pregnant women with PPROM (n = 51), TPROM (n = 283) and controls (n = 832) were enrolled. A weighted Cox model was applied to identify the GVs (single nucleotide polymorphisms [SNPs], insertions/deletions, and copy number variants) associated with either PPROM or TPROM. Gene set enrichment analysis (GSEA) was to explore the mechanisms. The suggestively significant GVs were applied to establish a random forest (RF) model. RESULTS: PTPRT variants (rs117950601, P = 4.37 × 10-9; rs147178603, P = 8.98 × 10-9) and SNRNP40 variant (rs117573344, P = 2.13 × 10-8) were associated with PPROM. STXBP5L variant (rs10511405, P = 4.66 × 10-8) was associated with TPROM. GSEA results showed that genes associated with PPROM were enriched in cell adhesion, and TPROM in ascorbate and glucuronidation metabolism. The area under the receiver operating characteristic curve of SNP-based RF model for PPROM was 0.961, with a sensitivity of 100.0% and specificity of 83.3%. DISCUSSION: Maternal GVs in PTPRT and SNRNP40 were associated with PPROM, and GV in STXBP5L was associated with TPROM. Cell adhesion participated in PPROM, while ascorbate and glucuronidation metabolism contributed in TPROM. The PPROM might be well predicted using the SNP-based RF model.

Preterm Prelabor Rupture of Membranes Linked to Vaginal Bacteriome of Pregnant Females in the Early Second Trimester: a Case-Cohort Design.

Preterm prelabor rupture of membranes (PPROM) is a major cause of spontaneous preterm birth (sPTB), one of the greatest challenges facing obstetrics with complicated pathogenesis. This case-cohort study investigated the association between vaginal bacteriome of singleton pregnant females in the early second trimester and PPROM. The study included 35,255 and 180 pregnant females with PPROM as cases and term-birth without prelabor rupture of membranes (TWPROM) and term prelabor rupture of membranes (TPROM) pregnant females as controls, respectively. Using 16S rRNA sequencing, the vaginal microbiome traits were analyzed. Females with PPROM had higher alpha and beta diversity (P < 0.05) than TWPROM and TPROM. The presence of L. mulieris was associated with a decreased risk of PPROM (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI]: 0.17-0.72) compared with TWPROM. Meanwhile, the presence of Megasphaera genus (aOR = 2.27; 95% CI: 1.09-4.70), Faecalibacterium genus (aOR = 3.29; 95% CI: 1.52-7.13), Bifidobacterium genus (aOR = 3.26; 95% CI: 1.47-7.24), Xanthomonadales genus (aOR = 2.76; 95% CI: 1.27-6.01), Gammaproteobacteria class (aOR = 2.36; 95% CI: 1.09-5.14), and Alphaproteobacteria class (aOR = 2.45; 95% CI: 1.14-5.26) was associated with an increased risk of PPROM compared with TWPROM. Our results indicated that the risk of PPROM can decrease with vaginal L. mulieris but increase with high alpha or beta diversity, and several vaginal bacteria in pregnant females may be involved in the occurrence of PPROM.

Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese.

BACKGROUND: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS: Genes related to lipolysis, redox reaction, and proliferation of islet ß-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women.

Objective: The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non-GDM groups, respectively. Study Design. To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case-cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non-GDM group were analyzed, respectively. Results: The proportion of GDM in the sPTB (19.51%) was higher than the controls (7.47%, P = 0.018). The vaginal microbiota of pregnant women with sPTB exhibited higher alpha diversity metrics (observed features, P = 0.001; Faith's phylogenetic diversity, P = 0.013) and different beta diversity metrics (unweighted UniFrac, P = 0.006; Jaccard's distance, P = 0.004), compared with controls. The presence of Lactobacillus paragasseri/gasseri (aOR: 3.12, 95% CI: 1.24-7.84), Streptococcus (aOR: 3.58, 95% CI: 1.68-7.65), or Proteobacteria (aOR: 3.39, 95% CI: 1.55-7.39) was associated with an increased risk of sPTB in the non-GDM group (P < 0.05). However, the relative abundance of novel L. mulieris (a new species of the L. delbrueckii group) was associated with a decreased risk of sPTB (false discovery rate, 0.10) in all pregnant women. Conclusion: GDM may modify the association of vaginal taxa with sPTB, suggesting that maternal GDM should be considered when using vaginal taxa to identify pregnant women at high risk of sPTB.

Management of acute exacerbation of chronic obstructive pulmonary disease under a tiered medical system in China.

BACKGROUND: The Chinese government has promoted the 'tiered medical services' policy in which diseases are classified by severity, mode of onset and difficulty of treatment since 2015 to optimize medical resources. We evaluated the diagnosis and treatment of acute exacerbation (AE) of chronic obstructive pulmonary disease (AECOPD) under the tiered system. METHODS: We conducted a cross-sectional study. COPD characteristics and treatments were compared among hospitals in different tiers. Associations were examined by univariate and multivariable logistic regression analysis. In addition, multivariate logistic regression was performed to identify the possible influencing factors of antibiotics, glucocorticoids and anticoagulant usages. RESULTS: Eligible COPD patients (n = 432) were consecutively recruited from eight hospitals in different tiers in China. Patients in the countryside preferred the community hospitals, whereas patients in cities preferred second-tier and teaching hospitals when they suffer from AECOPD. It indicates most COPD patients are likely to treat their disease locally. The severity of COPD AE increased with tiers of hospitals (p < 0.001). However, our results clearly show that most community hospitals can only deal with mild exacerbation of COPD. Approximately 90% of AE patients received antibiotics. We speculated that antibiotics abuse might exist in the three tiers of hospitals. Multivariate analysis demonstrated that long-term antibiotics usage (⩾14 days) was associated with moderate exacerbation [odds ratio (OR): 5.295, 95% confidence intervals (CI) 2.248-12.473, p < 0.001], radiographic progression (OR: 2.176, 95% CI: 1.047-4.522, p = 0.037), positive sputum etiology (OR: 3.073, 95% CI: 1.477-6.394, p = 0.003) and increased white blood cells (OR: 2.470, 95% CI: 1.190-5.126, p = 0.015). The proportion of glucocorticoids increased with the hospital hierarchy (18.6% versus 45.6% versus 69.2%, p < 0.001). The proportions of severe cases in the second-tier hospitals were 26.9%; however, non-invasive positive pressure ventilation (NPPV) rate was only 14.7%. Anticoagulant is not commonly used in AECOPD, and the community hospitals had the lowest proportion of anticoagulation regimen (1.7% versus 14.3% versus 20.5%, p = 0.002). CONCLUSIONS: The 'tiered medical services' policy in AECOPD management has been unsatisfactory in the past years. Irrational treatment strategies in different hospitals were still found when comparing with international guideline. Further reform of the policy is still needed to optimize the management of AECOPD in China.

Three-dimensional non-isothermal numerical model for predicting semi-volatile organic compound transport process in a room.

In this paper, a three-dimensional non-isothermal computational model for predicting indoor SVOC distribution is proposed, considering the effects of turbulence diffusion and suspended particles. The realizable k-ε model is introduced for turbulent flow simulation in a room. The Euler-Euler method is adopted to deal with the gas-particle two-phase flow coupled problem. Inertia slip velocity and irreversible first-order absorption boundary are employed for more accurate prediction of particle motion. The simulated curve of outlet gas-phase di-2-ethylhexyl phthalate (DEHP) concentration with emission time is verified by available experimental data. The emission process of DEHP in a 15 m2 room in Beijing during 100 days with or without air cleaner is simulated by the developed model considering air leak through window and door gaps. It is found that if the air cleaner keeps on all the time during 100 days the gas-phase DEHP concentration in the room will tend to be uniform, while the emission process is far from equilibrium without an air cleaner even the emission lasts 100 days. Results also suggest that floor heating, decrease of particle concentration, weaken of heat transfer, enhancement of mass transfer, and air infiltration in window gap contribute to decrease DEHP concentration.