Repeated radon exposure induced ATM kinase-mediated DNA damage response and protective autophagy in mice and human bronchial epithelial cells.

OBJECTIVE: Radon ( 222 Rn) is a naturally occurring radioactive gas that has been closely linked with the development of lung cancer. In this study, we investigated the radon-induced DNA strand breaks, a critical event in lung carcinogenesis, and the corresponding DNA damage response (DDR) in mice and human bronchial epithelial (BEAS-2B) cells. METHODS: Biomarkers of DNA double-strand breaks (DSBs), DNA repair response to DSBs, ataxia-telangiectasia mutated (ATM) kinase, autophagy, and a cell apoptosis signaling pathway as well as cell-cycle arrest and the rate of apoptosis were determined in mouse lung and BEAS-2B cells after radon exposure. RESULTS: Repeated radon exposure induced DSBs indicated by the increasing expressions of γ-Histone 2AX (H2AX) protein and H2AX gene in a time and dose-dependent manner. Additionally, a panel of ATM-dependent repair cascades [i.e. non-homologous DNA end joining (NHEJ), cell-cycle arrest and the p38 mitogen activated protein kinase (p38MAPK)/Bax apoptosis signaling pathway] as well as the autophagy process were activated. Inhibition of autophagy by 3-methyladenine pre-treatment partially reversed the expression of NHEJ-related genes induced by radon exposure in BEAS-2B cells. CONCLUSIONS: The findings demonstrated that long-term exposure to radon gas induced DNA lesions in the form of DSBs and a series of ATM-dependent DDR pathways. Activation of the ATM-mediated autophagy may provide a protective and pro-survival effect on radon-induced DSBs.

A noncanonical glycoprotein H complex enhances cytomegalovirus entry.

Human cytomegalovirus (HCMV) causes severe birth defects, lifelong health complications, and $4 billion in annual costs in the United States alone. A major challenge in vaccine design is the incomplete understanding of the diverse protein complexes the virus uses to infect cells. In Herpesviridae, the gH/gL glycoprotein heterodimer is expected to be a basal element of virion cell entry machinery. For HCMV, gH/gL forms a "trimer" with gO and a "pentamer" with UL128, UL130, and UL131A, with each complex binding distinct receptors to enter varied cell types. Here, we reveal a third glycoprotein complex, abundant in HCMV virions, which significantly enhances infection of endothelial cells. In this "3-mer" complex, gH, without gL, associates with UL116 and UL141, an immunoevasin previously known to function in an intracellular role. Cryo-EM reveals the virion-surface 3-mer is structurally unique among Herpesviridae gH complexes, with gH-only scaffolding, UL141-mediated dimerization and a heavily glycosylated UL116 cap. Given that antibodies directed at gH and UL141 each can restrict HCMV replication, our work highlights this virion surface complex as a new target for vaccines and antiviral therapies.

Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization.

BACKGROUND: The associations of gut microbial metabolites, such as trimethylamine N-oxide (TMAO), its precursors, and phenylacetylglutamine (PAGln), with the risk of gestational diabetes mellitus (GDM) remain unclear. METHODS: Serum samples of 201 women with GDM and 201 matched controls were collected and then targeted metabolomics was performed to examine the metabolites of interest. Multivariable conditional logistic regression was applied to investigate the relationship between metabolites and GDM. Meta-analysis was performed to combine our results and four similar articles searched from online databases, and Mendelian randomization (MR) analysis was eventually conducted to explore the causalities. RESULTS: In the case-control study, after dichotomization and comparing the higher versus the lower group, the adjusted odds ratio and 95% confidence interval of choline and L-carnitine with GDM were 2.124 (1.186-3.803) and 0.293 (0.134-0.638), respectively; but neutral relationships between TMAO, betaine, and PAGln with GDM were observed. The following meta-analysis consistently revealed that L-carnitine was negatively associated with GDM. However, MR analyses showed no evidence of causalities. CONCLUSIONS: Maternal levels of L-carnitine were related to the risk of GDM in both the original case-control study and meta-analysis. However, we did not observe any genetic evidence to establish a causal relationship between this metabolite and GDM.

Interpregnancy Interval After Healthy Live Birth and Subsequent Spontaneous Abortion.

Importance: Many studies have reported that the interpregnancy interval (IPI) is a potential modifiable risk factor for adverse perinatal outcomes. However, the association between IPI after live birth and subsequent spontaneous abortion (SA) is unclear. Objective: To investigate the association of IPI after a healthy live birth and subsequent SA. Design, Setting, and Participants: This prospective cohort study used data from 180 921 women aged 20 to 49 years who had a single healthy live birth and planned for another pregnancy and who participated in the Chinese National Free Prepregnancy Checkups Project from January 1, 2010, to December 31, 2020. Statistical analysis was conducted from June 20 to October 5, 2023. Exposure: Interpregnancy interval, defined as the interval between the delivery date and conception of the subsequent pregnancy, was categorized as follows: less than 18 months, 18 to 23 months, 24 to 35 months, 36 to 59 months, and 60 months or longer. Main Outcomes and Measures: The main outcome was SA. Multivariable-adjusted odds ratios (ORs) were calculated by logistic regression models to examine the association between IPI and the risk of SA. Dose-response associations were evaluated by restricted cubic splines. Results: The analyses included 180 921 multiparous women (mean [SD] age at current pregnancy, 26.3 [2.8] years); 4380 SA events (2.4% of all participants) were recorded. A J-shaped association between IPI levels and SA was identified. In the fully adjusted model, compared with IPIs of 18 to 23 months, both short (<18 months) and long (≥36 months) IPIs showed an increased risk of SA (IPIs of <18 months: OR, 1.15 [95% CI, 1.04-1.27]; IPIs of 36-59 months: OR, 1.28 [95% CI, 1.15-1.43]; IPIs of ≥60 months: OR, 2.13 [95% CI, 1.78-2.56]). Results of the subgroup analysis by mode of previous delivery were consistent with the main analysis. Conclusions and Relevance: This cohort study of multiparous women suggests that an IPI of shorter than 18 months or an IPI of 36 months or longer after a healthy live birth was associated with an increased risk of subsequent SA. The findings are valuable to make a rational prepregnancy plan and may facilitate the prevention of SA and improvement in neonatal outcomes.

Association between plasma growth differentiation factor 15 levels and pre-eclampsia in China.

Background: Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE). Method: The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results: MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI = 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions: These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

Evaluating eight indicators for identifying metabolic syndrome in Chinese and American adolescents.

BACKGROUND: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial. METHODS: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed. RESULTS: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI. CONCLUSIONS: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor. IMPACT: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators.

The impact of transcutaneous electrical acustimulation (TEA) on rectal distension-induced pain in patients with irritable bowel syndrome (IBS)-A study to determine the optimal TEA delivery modalities and effects on rectal sensation and autonomic function.

BACKGROUND: Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function. METHODS: Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment. KEY RESULTS: Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04). CONCLUSIONS & INFERENCES: TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients. DESIGN: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively. RESULTS: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7. CONCLUSION: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

Association between human blood metabolome and the risk of pre-eclampsia.

Pre-eclampsia is a complex multi-system pregnancy disorder with limited treatment options. Therefore, we aimed to screen for metabolites that have causal associations with preeclampsia and to predict target-mediated side effects based on Mendelian randomization (MR) analysis. A two-sample MR analysis was firstly conducted to systematically assess causal associations of blood metabolites with pre-eclampsia, by using metabolites related large-scale genome-wide association studies (GWASs) involving 147,827 European participants, as well as GWASs summary data about pre-eclampsia from the FinnGen consortium R8 release data that included 182,035 Finnish adult female subjects (5922 cases and 176,113 controls). Subsequently, a phenome-wide MR (Phe-MR) analysis was applied to assess the potential on-target side effects associated with hypothetical interventions that reduced the burden of pre-eclampsia by targeting identified metabolites. Four metabolites were identified as potential causal mediators for pre-eclampsia by using the inverse-variance weighted method, including cholesterol in large HDL (L-HDL-C) [odds ratio (OR): 0.88; 95% confidence interval (95% CI): 0.83-0.93; P = 2.14 × 10-5), cholesteryl esters in large HDL (L-HDL-CE) (OR: 0.88; 95% CI: 0.83-0.94; P = 5.93 × 10-5), free cholesterol in very large HDL (XL-HDL-FC) (OR: 0.88; 95% CI: 0.82-0.94; P = 1.10 × 10-4) and free cholesterol in large HDL (L-HDL-FC) (OR: 0.89; 95% CI: 0.84-0.95; P = 1.45 × 10-4). Phe-MR analysis showed that targeting L-HDL-CE had beneficial effects on the risk of 24 diseases from seven disease chapters. Based on this systematic MR analysis, L-HDL-C, L-HDL-CE, XL-HDL-FC, and L-HDL-FC were inversely associated with the risk of pre-eclampsia. Interestingly, L-HDL-CE may be a promising drug target for preventing pre-eclampsia with no predicted detrimental side effects. The study consists of a two-stage design that conducts MR at both stages. First, we assessed the causality for the associations between 194 blood metabolites and the risk of pre-eclampsia. Second, we investigated a broad spectrum of side effects associated with the targeting identified metabolites in 693 non-preeclampsia diseases. Our results suggested that Cholesteryl esters in large HDL may serve as a promising drug target for the prevention or treatment of pre-eclampsia with no predicted detrimental side effects.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia.

BACKGROUND: Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10, in "FD" rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE). METHODS: A rodent model of FD was established via neonatal treatment with intragastric iodoacetamide. After 8 weeks, the rats were implanted with electrodes at acupoint ST36 for EA. The plasma levels of cytokines and NE were measured using enzyme-linked immunosorbent assay. We explored the correlations of cytokine levels with NE levels and GE. KEY RESULTS: (i) "FD" rats demonstrated increased levels of TNF-α, IL-1ß, and IL-6 (p < 0.05 each) compared with the control rats. (ii) EA significantly decreased the plasma levels of TNF-α, IL-1ß, and IL-6 in "FD" rats (p < 0.05 each) compared with sham EA. (iii) The plasma levels of NE were positively correlated with those of IL-6 (r = 0.86, p < 0.05) and IL-1ß (r = 0.81, p < 0.05), whereas NE levels and GE were negatively correlated with IL-10 levels (r = -0.870, p < 0.05 and r = -0.791, p < 0.05, respectively). CONCLUSIONS: EA inhibits the release of proinflammatory cytokines probably via the suppression of sympathetic activity in "FD" rats.

Growth and development of syphilis-exposed and -unexposed uninfected children during their first 18 months of life in Suzhou, China: a nested case-control study with propensity score matching.

Background: With the successful implementation of Prevention of Mother-to-Child Transmission (PMTCT) policies, the proportion of infants with exposure to both syphilis and antibiotic medication in utero has increased in China, but there is limited evidence about the early growth and development of such infants. Methods: We conducted a retrospective nested case-control study based on data from the China PMTCT program conducted in Suzhou from 2016 to 2021. Propensity score matching (PSM) was employed to extract 826 syphilis-exposed but uninfected (SEU) infants and 1,652 syphilis-unexposed uninfected (SUU) infants from a total of 712,653 infants. Maternal characteristics were collected through questionnaires, such as parity, age, education level, smoking and drinking habits during pregnancy. Infantile characteristics were retrieved from medical records or via questionnaires, such as gestational age, gender, mode of delivery, Apgar scores, birth weight and length, outdoor time, vitamin D intake, and feed pattern. Mixed effects models, adjusting for potential influencing factors, were used to investigate the early infantile growth pattern of SEU and SUU infants. All statistical analysis were conducted using R (version 4.2.0). Results: Length and weight were slightly higher in SEU infants than in the SUU infants at some time points (months 0 and 18 for length, p-values <0.05; months 0, 6, and 18 for weight, p < 0.05). In the mixed effects model, SEU group was found to be associated with higher weight [exponentiated beta exp.(ß) = 1.15, 95% Confidence Interval (CI) = 1.06, 1.25], length [exp(ß) = 1.42, 95% CI = 1.14, 1.77], and BMI z-score [exp(ß) = 1.09, 95% CI = 1.00, 1.19]. Conclusion: With the effective prevention of congenital syphilis under the PMTCT program, SEU infants have non-inferior growth patterns during their first 18 months of life compared with SUU controls in Suzhou, China.

Noninvasive electrical neuromodulation for gastrointestinal motility disorders.

INTRODUCTION: Gastrointestinal motility disorders are highly prevalent without satisfactory treatment. noninvasive electrical neuromodulation is an emerging therapy for treating various gastrointestinal motility disorders. AREAS COVERED: In this review, several emerging noninvasive neuromodulation methods are introduced, including transcutaneous auricular vagal nerve stimulation, percutaneous auricular vagal nerve stimulation, transcutaneous cervical vagal nerve stimulation, transcutaneous electrical acustimulation, transabdominal interference stimulation, tibial nerve stimulation, and translumbosacral neuromodulation therapy. Their clinical applications in the most common gastrointestinal motility are discussed, including gastroesophageal reflux disease, functional dyspepsia, gastroparesis, functional constipation, irritable bowel syndrome, and fecal incontinence. PubMed database was searched from 1995 to June 2023 for relevant articles in English. EXPERT OPINION: Noninvasive neuromodulation is effective and safe in improving both gastrointestinal symptoms and dysmotility; it can be used when pharmacotherapy is ineffective. Future directions include refining the methodology, improving device development and understanding mechanisms of action.

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats.

Objectives: Sacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats. Methods: Experiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB). Key results: (1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p < 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p < 0.01); yet SNS normalized vagal activity. Conclusion: SNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRACT.

Prevalence of suicide ideation among HIV/AIDS patients in China: A systematic review and meta-analysis.

Objective: A systematic review and meta-analysis was performed to evaluate the prevalence of suicide ideation among HIV/AIDS patients in China. Methods: Systematic search of CNKI, Wanfang, China biology medicine database, Weipu, EMBASE, Web of science and PubMed for studies related to the suicide ideation of HIV/AIDS patients. The incidence of suicide ideation of HIV / AIDS patients in China was investigated by meta-analysis. Results: A total of 16 studies were included (n = 6,174). The incidence of suicidal ideation in HIV/AIDS patients was 30.6% (95%CI: 21.4-39.9%). The results of subgroup analysis showed that the incidence of suicidal ideation in male was 36.1%, which was higher than that in female (32.8%), homosexual patients (39.7%) higher than heterosexual patients (27.1%), 2013-2021 survey (35.2%) higher than 2003-2012 survey (26.5%), the unmarried patients (39.6%) were higher than the married patients (34.5%), the patients diagnosed >1 year (28.4%) were higher than the patients diagnosed <1 year (27.6%), and the depression patients (34.3%) were higher than patients without depression (20.5%) and CD4 cell counts ≤200 cells/ul group (20.6%) were higher than those in >400 cells/ul group (19.8%). Conclusion: The incidence of suicide ideation in HIV/AIDS patients in China is relatively high.

Ambient air pollutants in the first trimester of pregnancy and birth defects: an observational study.

OBJECTIVES: As current studies on the relationships between air pollutants exposure during the first trimester and birth defects were not fully elucidated, this study aimed to assess the association between selected air pollutants and birth defects. DESIGN: An observational study. PARTICIPANTS: We obtained 70 854 singletons with gestational age <20 weeks who were delivered at a large maternal and child healthcare centre in Wuhan, China. OUTCOME MEASURES: Birth defects data and daily average concentration of ambient particulate matter ≤10 µm diameter (PM10), PM ≤2.5 µm diameter (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were obtained. Logistic regression analysis was applied to assess the association between maternal air pollutants exposure during first trimester and total birth defects, congenital heart defects (CHDs), limb defects and orofacial clefts with adjustments of potential covariates. RESULTS: There were a total of 1352 birth defect cases included in this study, with a prevalence of 19.08‰. Maternal exposed to high concentrations of PM10, PM2.5, NO2 and SO2 in the first trimester were significantly associated with elevated ORs of birth defects (ORs ranged from 1.13 to 1.23). Additionally, for male fetuses, maternal exposed to high PM2.5 concentration was associated with an elevated odd of CHDs (OR 1.27, 95% CI 1.06 to 1.52). In the cold season, the ORs of birth defects were significantly increased among women exposed to PM2.5 (OR 1.64, 95% CI 1.41 to 1.91), NO2 (OR 1.22, 95% CI 1.08 to 1.38) and SO2 (OR 1.26, 95% CI 1.07 to 1.47). CONCLUSIONS: This study showed unfavourable effects of air pollutants exposure during the first trimester on birth defects. Especially, the association between maternal PM2.5 exposure and CHDs was only observed among male fetuses, and stronger effects of PM2.5, NO2 and SO2 exposure on birth defects were observed in the cold season.

Aspirin 75 mg to prevent preeclampsia in high-risk pregnancies: a retrospective real-world study in China.

BACKGROUND: Several randomized clinical trials showed that aspirin could decrease the incidence of preeclampsia (PE) in women at high risk, but data from sources other than traditional clinical trials that investigating the preventive effect of aspirin 75 mg on PE is still lacking, especially in mainland China. We aimed to use Chinese real-world data to estimate the preventive effect of low-dose aspirin (LDA) on PE. METHODS: Clinical data of pregnant women who were at high risk of PE and had their first prenatal visit at the affiliated Taicang People's Hospital of Soochow University during November 31, 2018 and May 10, 2021 was retrospectively analyzed. Among the 266 included pregnant women, 115 individuals treated with aspirin 75 mg per day and the other 151 without such treatment were considered as the LDA group and the control group, respectively. RESULTS: In the LDA group, 64 (55.65%) of 115 pregnant women took aspirin before 16 weeks of gestation. Besides, 12 (10.43%) and 34 (22.52%) women developed PE in the LDA group and control group, respectively; the aspirin prophylaxis was associated with a lower risk of PE (odds ratio = 0.40, 95% confidence interval = 0.20-0.82, P = 0.0098). In addition, LDA is slightly more effective when initiated before 16 weeks of gestation or in those without chronic hypertension, when compared with their counterparts. CONCLUSION: Prophylaxis with 75 mg per day of aspirin in high-risk women resulted in a significantly lower incidence of PE than that in the control group.

Association between growth differentiation factor 15 levels and gestational diabetes mellitus: A combined analysis.

Objective: Gestational diabetes mellitus (GDM) is a common glucose metabolism disease occurs in pregnancy that affects both maternal and neonatal health. Recently, increasing studies have attached importance to the relationship between growth differentiation factor 15 (GDF-15) and GDM, but the results were inconclusive. Therefore, we conducted a meta-analysis to examine the association between GDF-15 and GDM. Materials and methods: A systematical search was performed in Gene Expression Omnibus (GEO), PubMed and Google Scholar till Oct 27, 2022. We first calculated the mean and standard deviation of GDF-15 expression levels from the included eligible datasets and articles. Then, a meta-analysis was conducted to depict the difference in GDF-15 mRNA or GDF-15 protein expression between case and control groups by using conservative random effect model. Moreover, the potential publication bias was checked with the aid of Begg's test and Egger's test. Finally, sensitivity analyses were performed by changing the inclusion criteria. Results: In summary, 12 GEO datasets and 5 articles were enrolled in our study, including 789 GDM patients and 1202 non-GDM pregnant women. It was found that the expression levels of GDF-15 mRNA and GDF-15 protein in late pregnancy were significantly higher in GDM patients compared with non-GDM pregnant women, with the standard mean difference (SMD) and 95% confidence interval (95% CI) of 0.48 (0.14, 0.83) and 0.82 (0.32-1.33), respectively. Meanwhile, a slightly weakened association between GDF-15 protein levels and GDM was also observed in the middle pregnancy, with SMD (95% CI) of 0.53 (0.04-1.02). Conclusion: In all, our results suggested that the expression levels of GDF-15 were significantly higher in GDM patients compared with non-GDM pregnant women, especially in the late pregnancy.

Relationship Between Plasma Growth Differentiation Factor 15 Levels and Complications of Type 2 Diabetes Mellitus: A Cross-sectional Study.

OBJECTIVE: Our aim in this study was to identify the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in a community-based population in China. METHODS: Based on a cross-sectional study registered in the National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and tested further for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular (diabetic kidney disease [DKD], diabetic retinopathy, and neuropathy) complications were evaluated. Logistic regression models were conducted to identify the associations of GDF15 with the risk of diabetes complications, and linear regression models were used to assess relationships between GDF15 and other clinical features. RESULTS: Overall, 459 of the 1,689 T2DM patients (27.18%) had complications. GDF15 levels were significantly higher in patients with any type of complication compared with their counterparts. With each standard deviation increase of base 10 logarithms of GDF15 (lg-GDF15), the risk of overall complications increased by 1.17-fold (95% confidence interval [CI], 1.03 to 1.32). In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger (adjusted odds ratio [OR], 1.24; 95% CI, 1.08 to 1.43), especially for DKD (adjusted OR, 1.51; 95% CI, 1.19 to 1.93). Subgroup analyses showed that the strength of association between GDF15 and complications varied by distinct age and T2DM duration subgroups. Patients with 2 or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices. CONCLUSION: Higher GDF15 levels were associated with T2DM complications, especially DKD. GDF15 may serve as a biomarker for monitoring the deterioration of T2DM.