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Abstract Objective Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy. Methods A two‐sample MR analysis was conducted using genome‐wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR‐Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR‐Egger intercept test, and leave‐one‐out analysis, was applied to confirm the robustness of results. Results Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR‐Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave‐one‐out analysis validated the robustness of the results. Significance This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in‐depth understanding of the pathogenesis of epilepsy. Plain Language Summary Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.

Abstract Background Postpartum depression (PPD) is widely recognized as the most prevalent mental health crisis following childbirth and has been linked to sleep disturbances. However, the potential causal relationships between various sleep traits and PPD remain unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to investigate these associations. Methods The inverse-variance-weighted method was used to evaluate the causally linked sleep traits on postpartum depression. The weighted median, weighted mode, and MR-Egger were used to estimate the robustness of the inverse-variance-weighted method. The leave-one-out method estimated the sensitivity of the result. Cochran’s Q method was used for the heterogeneous test. The MR-Egger intercept and MR-PRESSO methods detected the horizontal pleiotropy. Results We examined the genetic causal relationships between nine sleep traits and postpartum depression. Sleep apnea syndrome (OR: 1.122; 95%CI: 1.063–1.185; p = 0.000), sleeplessness/insomnia (OR: 1.465; 95%CI: 1.104–1.943; p = 0.008), and frequency of tiredness/lethargy in last 2 weeks (OR: 1.725; 95%CI: 1.345–2.213; p = 0.000) genetically predicted the increased risk of postpartum depression. The reverse Mendelian randomization analysis showed PPD caused sleeplessness/insomnia (β: 0.006; 95%CI: 0.001–0.010; p = 0.016) and frequency of tiredness/lethargy in last 2 weeks (β: 0.007; 95%CI: 0.002–0.011; p = 0.004). The remaining six sleep traits showed no significant association with PPD. There was no heterogeneity or horizontal pleiotropy. Conclusions Genetic evidence reveals causal relationships between specific sleep traits and PPD, including sleep apnea syndrome, sleeplessness/insomnia, and tiredness. Whether certain sleep health indicators suggest a risk of postpartum depression or sleep issues that are caused by PPD, both may offer insights into the prevention and treatment of PPD.

Background: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, accounting for >15 % of cancer-related deaths in children. We analyzed the epidemiological statistical indicators of neuroblastoma and other peripheral nervous system tumors patients from 1990 to 2021 in Global Burden of Disease (GBD) 2021 database, aiming to provide valuable insights for public health interventions and clinical practices. Methods: Based on the GBD 2021 database, this study analyzed the incidence, mortality, prevalence, and Disability-Adjusted Life-Years (DALYs) of neuroblastoma and other peripheral nervous system tumors from 1990 to 2021, stratified by sociodemographic development index (SDI) and geographic regions. Cross-country inequalities analysis was conducted to quantify the SDI-related inequality of disease burden across countries. In addition, the average annual percentage change (AAPC) and Age-Period-Cohort (APC) model were used to evaluate the trend of disease burden, while the global burden of disease to 2035 was predicted by Bayesian Age-Period-Cohort (BAPC) model. Findings: This study reported the disease burden of neuroblastoma and other peripheral nervous system tumors in GBD 2021 database for the first time. Globally, the incidence and mortality of neuroblastoma have increased year by year from 1990 to 2021, especially in regions with low SDI, such as South Asia and sub-Saharan Africa, where the burden of disease has increased significantly. Regions with high SDI, such as North America and Western Europe, have seen a reduction in disease burden due to higher levels of medical care and earlier diagnosis. The age distribution shows that children under 5 years of age are mainly affected, especially in low- and middle-income areas. In addition, the incidence is slightly higher in men than in women. The BAPC model predicts that the global incidence, mortality, and DALYs of neuroblastoma will continue to increase until 2035. Interpretation: Significant regional and population variation in neuroblastoma and other peripheral nervous system tumors worldwide, with a particularly high disease burden in low SDI areas with limited medical resources. This trend highlights the urgent need for global public health interventions and resource allocation, particularly in low-income countries. Future research should focus on improving early diagnosis, risk stratification and target therapy in order to reduce the global burden of disease and improve patients’ prognosis. Funding: This study was supported by National Natural Science Foundation of China (No. 82293662, No 82172357 and No 81930066), Key project of Shanghai ''Science and Technology Innovation Action Plan (22JC1402304) and Research fund of Shanghai Municipal Health Bureau (No. 2019cxjq03).

BackgroundInflammatory bowel disease (IBD) has been reported to be associated with risk of uterine cervical neoplasm. We aimed to evaluate the causal relationship between IBD and uterine cervical neoplasm using a bidirectional Mendelian randomization analysis.MethodsWe derived instrumental variables for IBD, including Crohn’s disease and ulcerative colitis, from the IEU Open genome-wide association study (GWAS) database, and for the histological subtypes of uterine cervical neoplasm from the FinnGen repository’s GWAS data. The collected GWAS data predominantly represent individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as primary analysis approach.ResultsIBD (IVW odds ratio = 1.127, 95% confidence interval = 1.016–1.251; p = 0.024) and CD (IVW odds ratio = 1.119, 95% confidence interval = 1.023–1.224; p = 0.014) exhibited a significant causal effect on malignant cervical carcinoma. Sensitivity analyses confirmed these findings.ConclusionGenetically predicted IBD and CD are risk factors for the development of malignant cervical carcinoma. Patients with IBD and CD require specific attention to prevent cervical squamous cell carcinoma. Further studies to elucidate the underlying mechanisms may reveal new therapeutic targets.

Introduction Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. Methods Mendelian randomization (MR) study was used to analyze the genomewide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). Results After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013–1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039– 5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013–1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161–1.538; p

IntroductionThe relationship between serum uric acid (SUA) and cervical cancer is inconclusive. This study aims to investigate the causal relationship between SUA levels and cervical cancer incidence, and to evaluate the potential role of nutritional interventions in cervical cancer prevention.MethodsWe conducted a two-sample bidirectional Mendelian randomization (MR) analysis using genetic instruments from publicly available genome-wide association studies (GWASs) of individuals of predominantly European ancestry. Methods such as inversevariance weighted, weighted-median, weighted model, and MR-Egger were applied. Sensitivity tests, including leave-one-out, MR-PRESSO, and Cochran’s Q test, assessed heterogeneity and pleiotropy.ResultsOur findings revealed that a high SUA concentration significantly increased the risk of malignant cervical cancer: a 1 mg/mL increase in SUA was associated with a 71% higher risk (OR = 1.71, 95% CI = 1.10–2.67; p = 0.018). Stratification by histological type showed a significant causal effect on cervical adenocarcinoma risk (OR = 2.56, 95% CI = 1.14–5.73; p = 0.023). However, no clear evidence was found for a causal effect of cervical cancer on SUA levels.ConclusionThis study identified a causal relationship between elevated SUA levels and the risk of malignant cervical cancer, particularly cervical adenocarcinoma. These findings provide novel insights into the mechanisms of cervical carcinogenesis and suggest that managing SUA levels could be a potential strategy for cervical cancer prevention through dietary management.

Platelets are crucial for maintaining physiological equilibrium, thrombosis formation, inflammation, bacterial defense, wound repair, angiogenesis, and tumorigenesis. In the Pediatric Intensive Care Unit (PICU), children frequently exhibit platelet reductions or functional alterations due to diverse pathological conditions, which significantly influence disease progression and therapeutic approaches. We analyzed the association between platelets count and its derived parameters and all-cause mortality. Adjusted smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between proportional risk between platelets and all-cause mortality. Of the 11625 children, 677 (5.82%) died. After adjusting for confounders, there was a negative association between platelets and the risk of all-cause mortality in PICU. For every 100 × 10^9/L increase in platelets, the risk of death was reduced by 17% (adjusted OR = 0.83, 95% CI: 0.78, 0.89). The results of sensitivity analysis showed that in different stratified analyses (age, ICU category,WBC Count), the effect of platelets count on all-cause mortality remained stable. After adjusting for inflammation, nutrition, and liver function factors, platelets reduction is still an independent risk factor for PICU all-cause mortality.

PurposeStudies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear.MethodsA two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations.ResultsThe IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.06–1.40, p = 0.004], serous ovarian cancer (OR = 1.29, 95% CI: 1.10–1.52, p = 0.002), invasive mucinous ovarian cancer (OR = 1.24, 95% CI: 1.08–1.44, p = 0.003), clear cell ovarian cancer (OR = 1.25, 95% CI: 1.03–1.51, p = 0.023), breast cancer (OR = 1.07, 95% CI: 1.02–1.11, p = 0.002), and brain tumor (OR = 1.23, 95% CI: 1.06–1.42, p = 0.007). Conversely, genetically predicted UL reduced the risk of gastric cancer (OR = 0.91, 95% CI: 0.85–0.98, p = 0.008). The causal effects were consistent in the sensitivity analysis.ConclusionsOur results demonstrated that UL exhibits a causal relationship with high risk of several cancers. We suggest reinforcing the cancer screening in UL patients to enable the early detection of cancers.

PurposeTo investigate the potential causal association between COVID-19 exposure and optic nerve and visual pathway disorders through a two-sample bidirectional Mendelian randomization (MR) analysis, and to provide empirical support for the lung-brain axis.MethodsThis MR analysis utilized publicly accessible summary-level data from genome-wide association studies on COVID-19 (n=158,783) and optic nerve and visual pathway diseases (n=412,181), primarily involving individuals of European descent. The random-effect inverse-variance weighted estimation was applied as the main analytical approach, complemented by MR-Egger, weighted median, and weighted mode methods. The heterogeneity and pleiotropy of the instrumental variables were assessed using Cochran’s Q test, leave-one-out sensitivity analysis, MR-Egger intercept test, MR-PRESSO, and funnel plot evaluations.ResultsIn the forward analysis, the inverse-variance weighted method identified a significant causal effect of COVID-19 on optic nerve and visual pathway disorders (odds ratio = 1.697, 95% confidence interval: 1.086–2.652, p = 0.020). Directionally consistent results were also observed with MR-Egger regression, weighted median, and weighted mode approaches. Conversely, the reverse analysis revealed no causal effects of optic nerve and visual pathway disorders on COVID-19 susceptibility.ConclusionOur findings suggest that COVID-19 exposure may increase the risk of developing optic nerve and visual pathway disorders, supporting the lung-brain axis hypothesis. These results underscore the importance of vigilant monitoring of the visual system in patients recovering from COVID-19 and suggest potential avenues for future therapeutic strategies.

Background: The link between peripheral blood leukocyte telomere length (LTL) and endometriosis has remained uncertain. In order to investigate this association, a two-sample Mendelian randomization(MR) analysis was performed. Methods: We extracted Single-nucleotide polymorphisms (SNPs) associated with LTL from a published genome-wide association study (GWAS) comprising 472,174 individuals. Data on endometriosis, including its seven subtypes, were sourced from the iue open gwas project. Four methods were employed for MR: Inverse-variance weighted analysis (IVW), Mendelian randomization-Egger regression (MR Egger), weighted-median analysis, and Weighted Mode. Results: Genetically determined LTL was identified as a factor that can promote the occurrence of endometriosis. With every 1-SD increase in LTL, the risk of endometriosis increased by 26 % (OR = 1.260, 95 % CI = 1.073 to 1.479; P = 0.005). Genetically determined LTL also contributed to endometriosis subtypes: intestine (OR = 3.584, 95 % CI = 1.597 to 8.041; P = 0.002), ovary (OR = 1.308, 95 % CI = 1.033 to 1.655; P = 0.026), rectovaginal septum and vagina (OR = 1.360, 95 % CI = 1.000 to 1.851; P = 0.049). There was no observed causal relationship between LTL and the other four subtypes. Conclusion: This study, utilizing genetic data, offers evidence that longer LTL may cause increased risks of endometriosis, specifically endometriosis of the intestine, ovary, rectovaginal septum and vagina. These findings not only suggest that LTL may serve as a predictive factor for assessing the prevalence of three endometriosis subtypes but also provide new insights into the study of endometriosis pathogenesis.

BackgroundThe causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis.MethodsThe single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings.ResultsThe IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF.ConclusionThe study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA.

The study aimed to explore the relationship between the expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1), vitamin D, and impaired T cell subsets in recurrent spontaneous miscarriage (RSM). A Total of 779 healthy women of childbearing age and 1031 women with a history of RSM were involved in this study. The results of flow cytometry showed that the proportion of Tregs was higher in healthy women than in the women with RSM. For cytokines, the levels of interleukin-17 (IL-17) and interferon-gamma (IFN-γ) were significantly higher in RSM patients than in healthy women, while IL-10 was notably lower in RSM patients. Furthermore, compared to healthy individuals, RSM patients had lower levels of serum 25(OH)D detected by chemiluminescence. The frequency of Tregs was negatively correlated with 25(OH)D. Specifically, for every 10 ng/ml increase in 25(OH)D, the percentage of Tregs increased by 0.58 as calculated. IL-17 and IFN-γ were inversely correlated with 25(OH)D, while the serum interleukin-10 (IL-10) level was positively correlated with 25(OH)D. CYP27B1 was found to be expressed in both cytotrophoblast and extracellular villi trophoblast cells. However, reduced expression of CYP27B1 was observed in the placenta with RSM. Notably, the level of 25(OH)D increased in the supernatant of CYP27B1 knockdown BeWo compared to normal cells, while human chorionic gonadotropin (hCG) was significantly reduced. The hCG secretion of CYP27B1 KO BeWo cells was partially restored after 1,25(OH)2D3 supplementation. In addition, 1,25(OH)2D3 treatment could induce more CD4+ T cells to convert to Foxp3+iTreg, which in turn inhibited the secretion of IL-17, IFN-γ. In summary, this research unveiled a connection between reduced CYP27B1 and vitamin D deficiency in RSM. Our study underscores the potential benefits of vitamin D treatment supplementation in the context of RSM. However, it is important to note that further research is imperative to validate these observations.

Objectives: The incidence of cervical cancer increases every year during pregnancy. Cervical cytology in pregnant women has a unique morphology and liquid-based cytology methods are prone to cause false positives. The aim of this study was to investigate the serum cytokeratin 19 fragment antigen 21–1 (CYFRA21–1) and squamous cell carcinoma associated antigen (SCC-Ag) concentrations in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy. Methods: In this prospective study, 165 healthy non-pregnant women, 441 healthy pregnant women and 22 patients with cervical cancer in pregnancy were recruited. The healthy pregnant women group included 143 women in the first trimester (T1), 147 in the second (T2) and 151 in the third (T3). Results: Both SCC-Ag and CYFRA21–1 levels were significantly different in the healthy pregnant women group compared to the control group. The CYFRA21–1 and SCC-Ag were higher in the T1 and T3 than in the control groups. However, there was no statistically significant difference in serum CYFRA21–1 and SCC-Ag levels in the T2 group compared to the control group. The AUCs of CYFRA21–1, SCC-Ag and CYFRA21–1 combined with SCC-Ag were 0.674, 0.792, and 0.805, respectively. The cut-off values of CYFRA21–1 and SCC-Ag were 6.64 ng/mL and 1.75 ng/mL, respectively. Conclusions: Serum CYFRA21–1 and SCC-Ag levels were higher in pregnant women during early and late pregnancy compared to non-pregnant individuals, while they were not statistically different from non-pregnant women during mid-trimester. CYFRA21–1 and SCC-Ag have diagnostic value for cervical cancer in pregnancy.

ObjectiveOur aim was to assess the relationship between serum cholinesterase levels at intensive care unit admission and all-cause mortality in the pediatric intensive care unit.MethodsWe used the pediatric intensive care unit database (a large pediatric intensive care database in China from 2010 to 2018) to conduct a retrospective analysis to evaluate the serum cholinesterase levels at intensive care unit admission of 11,751 critically ill children enrolled to the intensive care unit. We analyzed the association between serum cholinesterase and all-cause mortality. Adjusted smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between proportional risk between serum cholinesterase and death.ResultsOf the 11,751 children, 703 (5.98%) died in hospital. After adjusting for confounders, there was a negative association between serum cholinesterase and the risk of death in pediatric intensive care unit. For every 1,000 U/L increase in serum cholinesterase, the risk of death was reduced by 16% (adjusted OR = 0.84, 95% CI: 0.79, 0.89). The results of sensitivity analysis showed that in different stratified analyses (age, intensive care unit category, albumin, alanine aminotransferase, creatinine, neutrophils), the effect of serum cholinesterase on all-cause mortality remained stable.ConclusionAfter adjusting for inflammation, nutrition, and liver function factors, cholinesterase reduction is still an independent risk factor for pediatric intensive care unit all-cause mortality.

BackgroundMetabolic disturbances and immune alterations caused by diabetes are not just bystanders of HPV infection, but the conclusion that diabetes increases the risk of HPV infection requires more clinical epidemiological evidence to confirm. Our aim was to evaluate the association of diabetes with HPV infection risk in female patients aged over 50 years in the cervical clinic.MethodsWe conducted a cross-sectional study of 6402 women aged over 50 years in the cervical clinic between May 2019 and March 2022 from China’s largest academic woman’s hospital. The quantitative-effect relationship between diabetes and HPV infection was observed by dose-response graph. Segmented multivariate logistic regression analysis was conducted to estimate the relative risk of HPV infection in diabetes patients. Multivariable predicted marginal proportions from logistic regression models were used to compute adjusted risk ratios.ResultsThere is a nonlinear relationship between HbA1c and the risk of HPV infection. When the HbA1c exceeds 5.7%, there is a saturation effect. After adjustment for confounders, the risk ratio for HPV infection in women with prediabetes was 1.09 (95% CI: 1.00-1.18) compared with women with HbA1c

BackgroundDiabetes causes metabolic disorders and immune changes that may be potential triggers of cervical cancer. Therefore, diabetes is not a “bystander” to cervical cancer. However, the conclusion that diabetes promotes cervical cancer lacks clinical epidemiological evidence, and the reported potential association between diabetes and cervical cancer is controversial.MethodsWe conducted an explorative cross-sectional study of 791 women with cytological HGSIL and HR-HPV, who attended the cervical clinic of the largest academic women’s hospital in China from May 2019 to March 2022. After cervical screening, patients who were requiring colposcopy were tested for HbA1c. HbA1c level of 6.5% or higher defines diabetes and HbA1c level of 5.7%-6.4% was defined as prediabetes. The relationship between diabetes and cervical cancer was observed by a dose-response graph. Subgroup analysis and multivariate logistic regression analysis were conducted to estimate the associations between diabetes and cervical cancer.ResultsAmong HGSIL patients with high-risk HPV infection, compared with women with HbA1c

AIMS: Extensive evidence suggests inflammatory components participate in the pathogenic processes of acute coronary syndromes (ACS). In this study, we aimed to elucidate the role and mechanism underlying the imbalance of Th17 and Treg cell peripheral populations in the pathogenesis of ACS. METHODS AND RESULTS: Using a flow cytometric analysis, we observed a significantly increased frequency of Th17 cells and a concurrently decreased CD4(+)CD25(+)Foxp3(+) Treg cells in patients with ACS. To elucidate the mechanism of Th17/Treg imbalance in ACS, 22 inflammatory cytokines were measured using multiplexed immunobead-based assays. Of six elevated cytokines in ACS patients, only IL-6 was positively correlated with a higher Th17 cell level (r = 0.39, P

Background: The causal relationship between sex hormone-binding globulin (SHBG) and neuroblastoma remains unknown. This study aimed to explore the causality between SHBG and the risk of neuroblastoma using bidirectional two-sample Mendelian randomization (MR) study. Methods: Instrumental variables associated with SHBG were obtained from the genome-wide association study (GWAS) of European containing 214,989 females and 185,221 males from the UK Biobank. Summary-level data for neuroblastoma were derived from the IEU OpenGWAS project with 1,627 patients and 3,254 controls. The inverse-variance weighted (IVW) method served as the primary analytic tool. Results: The IVW method revealed a significant positive causal relationship between male SHBG and the risk of neuroblastoma [OR, 2.169; 95% confidence interval (CI), 1.207-3.897; P = 0.010]. Conversely, female SHBG showed no significant causal link with neuroblastoma (IVW OR, 1.004; 95% CI, 0.542-1.860; P = 0.990). No significant reverse causality was detected. Sensitivity analyses validated these findings. Conclusions: Elevated SHBG levels in males, but not in females, can causally increase the risk of neuroblastoma. This gender-specific effect indicates a potential differential role of SHBG in the etiology of neuroblastoma. Further research is needed to elucidate the underlying mechanisms of this gender disparity. Monitoring SHBG levels, especially in males, could be pivotal in neuroblastoma risk assessment and management. [ABSTRACT FROM AUTHOR]

INTRODUCTION Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (0R=1.001; 95% CI: 0.999-1.003; p=0.224), LC (0R=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged. [ABSTRACT FROM AUTHOR]

Context: Elevated serum uric acid may be closely related to the occurrence of gestational diabetes mellitus (GDM). Objective: We aimed to elucidate the relationship between changes in serum uric acid before 24 weeks of gestation and the risk of GDM and associated adverse pregnancy outcomes and provide clinical epidemiological evidence for the involvement of uric acid in the etiology of GDM. Methods: We conducted a retrospective cohort study of 23 843 singleton pregnant women between February 2018 and June 2022. The exposure factor was serum uric acid before 24 weeks of gestation, primary outcome was gestational diabetes diagnosed at 24 to 28 weeks of gestation, and secondary outcomes were GDM A2 (GDM requiring pharmacotherapy), GDM combined with pre-eclampsia, preterm delivery, and large for gestational age infants. Adjusted risk ratios (RRs) were calculated using multivariate predictive marginal proportions from logistic regression models. Results: Among 23 843 singleton pregnant women, 3204 (13.44%) were diagnosed with GDM at 24 to 28 weeks of gestation, and elevated uric acid before 24 weeks of gestation was strongly associated with the risk of GDM. Compared with uric acid <240 µmol/L, the RR for GDM was 1.43 (95% CI 1.29-1.56) when uric acid was between 240 and 300 µmol/L; when uric acid was >300 µmol/L, the RR for GDM was 1.82 (95% CI 1.55- 2.15). In secondary outcomes uric acid had a similar relationship with GDM A2, preterm birth, and GDM combined with pre-eclampsia. Conclusion: Elevated uric acid levels before 24 weeks of gestation are associated with subsequent GDM; the best time to test for uric acid is before 18 weeks of gestation. Pregnant women with low and intermediate risk for GDM development may benefit more from serum uric acid measurements before 18 weeks of gestation. [ABSTRACT FROM AUTHOR]

In our multicenter study, we studied the distribution of Candida species in vulvovaginal candidiasis patients and investigated antifungal susceptibility profile and genotype of Candida albicans in vaginal swab. A total of 115 Candida albicans strains were detected in 135 clinical isolates. Minimum inhibitory concentration determinations showed that 83% and 81% of the 115 Candida albicans strains were susceptible to fluconazole and voriconazole. Randomly amplified polymorphic DNA analysis (RAPD) was applied to identify clonally related isolates from different patients at the local level. All tested strains were classified into genotype A (77.4%), genotype B (18.3%), and genotype C (4.3%). Genotype A was further classified into five subtypes and genotype B into two subtypes. Candida albicans was the dominant pathogen of vulvovaginal candidiasis, the majority belonging to genotype A in this study. Exposure to azoles is a risk factor for the emergence of azole resistance among Candida albicans isolated from VVC patients. [ABSTRACT FROM AUTHOR]