Causal relationship between genetically predicted uterine leiomyoma and cancer risk: a two-sample Mendelian randomization.

Purpose: Studies 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. Methods: A 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. Results: The 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. Conclusions: Our 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.

Reduced Platelets Associated with All-Cause Mortality in the Pediatric Intensive Care Unit.

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.

Elevated blood pressure: a genetically determined risk factor for cerebral artery dissection.

BACKGROUND: We aim to investigate the potential causal link between blood pressure (BP) levels and cerebral artery dissection (CAD) risk employing a two-sample Mendelian randomization (TSMR) framework. METHODS: Utilizing large-scale genome-wide association studies (GWAS)-retrieved data, we employed various MR techniques, including inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode, to ascertain BP's causal impact on CAD. The MR-Egger intercept was calculated to assess pleiotropy presence, determining heterogeneity by Cochran's Q statistic. RESULTS: The findings highlighted a significant association between elevated systolic BP (SBP; IVW: OR=3.09, 95% CI: 1.11-8.61, p=0.031) and increased diastolic BP (DBP; IVW: OR=2.17, 95% CI: 1.14-6.21, p=0.023) with CAD risk. Sensitivity analyses reinforced the robustness and reliability of these results. CONCLUSIONS: The results from this TSMR study suggest a causal link between high SBP and DBP and the increased likelihood of CAD, which provide genetic evidence for a reduced risk of CAD under blood pressure control.

Peripheral blood leukocyte Telomere length and endometriosis: A Mendelian randomization study.

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.

Causal effect of COVID-19 on optic nerve and visual pathway disorders: genetic evidence of lung-brain axis.

Purpose: To 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. Methods: This 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. Results: In 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. Conclusion: Our 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.

Causal Relationship Between Circulating Immune Cells and Recurrent Spontaneous Abortion: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious and common complication of pregnancy caused by multiple factors. The etiology remains incompletely understood, but immunologic factors play important roles. Here, we aimed to evaluate whether circulating immune cells causally impacted RSA. METHODS: In this study, we conducted a comprehensive two-sample Mendelian randomization (MR) study to determine the causal association between the 731 immunophenotypes of human peripheral blood lymphocytes and the number of spontaneous abortions as well as recurrent miscarriage. Sensitivity analyses were performed to assess and minimize heterogeneity and horizontal pleiotropy. Reverse MR analysis was used to assess reverse causality. RESULTS: After Bonferroni-correction, eight immunophenotypes were significantly associated with the number of spontaneous abortions: FSC-A on CD4+ T cell (beta = -0.051, 95% CI = [-0.085, -0.017], P-value = 0.004), CD8 on HLA DR+ CD8+ T cell (beta = -0.040, 95% CI = [-0.067, -0.014], P-value = 0.003), HLA DR on CD33dim HLA DR+ CD11b- (beta = -0.021, 95% CI = [-0.036, -0.005], P-value = 0.010), HLA DR+ T cell Absolute Count (beta = 0.022, 95% CI = [0.006, 0.037], P-value = 0.008), HLA DR+ T cell % lymphocyte (beta = 0.026, 95% CI = [0.010, 0.041], P-value = 0.001), HLA DR+ T cell % T cell (beta = 0.023, 95% CI = [0.007, 0.039], P-value = 0.004), HLA DR+ CD4+ T cell % lymphocyte (beta = 0.034, 95% CI = [0.007, 0.060], P-value = 0.012), and HLA DR on B cell (beta = 0.012, 95% CI = [0.003, 0.021], P-value = 0.010). In addition, we identified two immunophenotypes associated with recurrent miscarriage: HLA DR on B cell (OR = 0.854, 95% CI = [0.757, 0.964], P-value = 0.011), and CD19 on naive-mature B cell (OR = 4.595, 95% CI = [1.674, 12.617], P-value = 0.003). There was no evidence of heterogeneity, horizontal pleiotropy and reverse causality. CONCLUSIONS: Our study demonstrated a tight link between adaptive immune cells and RSA through genetic means, thus providing potential therapeutic targets or novel diagnostic biomarkers.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

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 (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=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.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. AIM: To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. METHODS: The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. RESULTS: Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). CONCLUSION: D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort.

Background: The 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. Methods: The 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. Results: The 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. Conclusion: The 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.

Causal effects of neuroticism on postpartum depression: a bidirectional mendelian randomization study.

PURPOSE: Postpartum depression (PPD) brings adverse and serious consequences to both new parents and newborns. Neuroticism affects PPD, which remains controversial for confounding factors and reverse causality in cross-sectional research. Therefore, mendelian randomization (MR) study has been adopted to investigate their causal relationship. METHODS: This study utilized large-scale genome-wide association study genetic pooled data from three major databases: the United Kingdom Biobank, the European Bioinformatics Institute, and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results' robustness, heterogeneity, and horizontal pleiotropy. The fixed effect model yielded the results of meta-analysis. RESULTS: In the IVW model, a meta-analysis of the MR study showed that neuroticism increased the risk of PPD (OR, 1.17; 95% CI, 1.11-1.25, p < 0.01). Reverse analysis showed that PPD could not genetically predict neuroticism. There was no significant heterogeneity or horizontal pleiotropy bias in this result. CONCLUSION: Our study suggests neuroticism is the risk factor for PPD from a gene perspective and PPD is not the risk factor for neuroticism. This finding may provide new insights into prevention and intervention strategies for PPD according to early detection of neuroticism.

Causal Relationship between Sex Hormone-Binding Globulin and Risk of Neuroblastoma: A Bidirectional Two-Sample Mendelian Randomization Study.

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. IMPACT: This study highlights a novel gender-specific aspect in the risk of neuroblastoma, emphasizing the potential role of male SHBG levels in neuroblastoma incidence, and sets the stage for targeted preventative strategies and further investigation into gender-based biological mechanisms.

CPY27B1-related vitamin D deficiency contributes to the impaired function of CD4+T cells in Recurrent spontaneous miscarriage.

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.

Serum CYFRA21-1 and SCC-Ag levels in women during pregnancy and their diagnostic value for cervical cancer.

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.

Association of serum inhibin a with pre-eclampsia: An observational cohort study with propensity score matching.

OBJECTIVE: To assess whether serum inhibin A at 14-20 weeks of gestation is associated with the occurrence of pre-eclampsia. METHODS: A retrospective cohort study using propensity score matching was conducted on 11 682 singleton pregnant women with established deliveries at the Obstetrics and Gynecology Hospital of Fudan University between January 2017 and July 2019. We investigated serum inhibin A levels at 14-20 weeks of gestation and calculated the relative risk between inhibin A and pre-eclampsia by multifactorial logistic regression analysis. Smoothed, fitted curves were used to observe the effect of inhibin A in relation to the occurrence of pre-eclampsia. RESULTS: The risk of pre-eclampsia occurrence increased with elevated serum inhibin A. After full adjustment for confounders, the risk ratio for pre-eclampsia in the group of pregnant women with high inhibin A was 2.92 (95% confidence interval [CI] 2.08-4.11) compared with those with normal inhibin A. The results of sensitivity analysis suggested a consistent effect of inhibin A on the risk of pre-eclampsia in different populations. CONCLUSION: Elevated serum inhibin A at 14-20 weeks of gestation is associated with pre-eclampsia and may provide an early warning signal for pregnancy outcomes associated with pre-eclampsia.

A new nomogram for the individualized prediction of children's mortality risk in pediatric intensive care unit.

OBJECTIVE: We developed a new nomogram for the prediction of mortality risk in children in pediatric intensive care units (PICU). METHODS: We conducted a retrospective analysis using the PICU Public Database, a study that included a total of 10,538 children, to develop a new risk model for mortality in children in the intensive care units (ICU). The prediction model was analyzed using multivariate logistic regression with predictors including age and physiological indicators, and the prediction model was presented as a nomogram. The performance of the nomogram was evaluated based on its discriminative power and was internally validated. RESULTS: Predictors contained in the individualized prediction nomogram included the neutrophils, platelets, albumin, lactate, oxygen saturation (P<0.1). The area under the receiver operating characteristic (ROC) curve for this prediction model is 0.7638 (95% CI: 0.7415-0.7861), which has effective discriminatory power. The area under the ROC curve of the prediction model in the validation dataset is 0.7404 (95% CI: 0.7016-0.7793), which is still effectively discriminative. CONCLUSION: The mortality risk prediction model constructed in this study can be easily used for individualized prediction of mortality risk in children in pediatric intensive care units.

Elevated Serum Uric Acid Is Associated With Gestational Diabetes Mellitus: An Observational Cohort Study.

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.

Abnormal uterine artery Doppler ultrasound during gestational 21-23 weeks associated with pre-eclampsia.

OBJECTIVE: To assess whether abnormal uterine artery Doppler ultrasound during weeks 21-23 of pregnancy was associated with an increased risk of pre-eclampsia. METHODS: Our retrospective cohort study analyzed uterine artery ultrasound parameters in singleton pregnant women at 21-23 weeks of pregnancy and assessed the association between abnormal ultrasound findings and the risk of pre-eclampsia. Multivariate logistic regression analysis was conducted to estimate the relative risk between uterine artery ultrasound and pre-eclampsia. RESULTS: Compared with normal results, unilateral pulsatile index abnormality (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.71-3.10), bilateral pulsatile index anomalies (OR 6.21, 95% CI 3.53-10.95), unilateral resistance index abnormality (OR 2.36, 95% CI 1.75-3.17), bilateral resistance index anomalies (OR 2.83, 95% CI 1.27-6.32), unilateral notch (OR 3.66, 95% CI 2.03-6.62), bilateral notch (OR 5.80, 95% CI 3.30-10.20) were associated with pre-eclampsia. For every 0.1 increase in the median multiple of mean pulsatile index, the risk of pre-eclampsia increased by 13%; for every 0.1 increase in the median multiple of mean resistance index, the risk of pre-eclampsia increased by 22%. CONCLUSION: Multiples of the median for the pulsatile and resistance indices are an effective evaluation tool. Abnormal uterine artery ultrasound indices are strongly associated with the development of pre-eclampsia.

Association of first trimester serum uric acid with preeclampsia: an observational cohort study with propensity score matching.

To elucidate whether uric acid changes in early pregnancy are associated with the development of preeclampsia and their association with preeclampsia-related adverse pregnancy outcomes. We conducted a retrospective cohort study of 4725 singleton pregnant women between January 2017 and July 2019 using propensity score matching. The primary outcome of the cohort was preeclampsia, and the secondary outcomes were preterm delivery, preterm preeclampsia and low birth weight infants. Multivariable predicted marginal proportions from logistic regression models were used to compute adjusted risk ratios. The quantitative-effect relationship between serum uric acid and preeclampsia development was observed by a dose‒response graph, and the effect of serum uric acid on the week of gestation at delivery was assessed using the Kaplan‒Meier method and the log-rank test. The risk of preeclampsia development increased with higher serum uric acid levels. After adjusting for confounders, the risk ratio for the development of preeclampsia with uric acid levels ≥240 µmol/l was 1.25 (95% CI: 0.96-1.65) compared with the group with uric acid levels <240 µmol/l. In the subgroup analysis of KM (Kaplan-Meier) curves, the gestational week at delivery was earlier when uric acid levels ≥240 µmol/l occurred at 8-12 weeks of gestation. Elevated serum uric acid levels before 20 weeks of gestation are associated with the development of preeclampsia, especially in the first 8-12 weeks of gestation, and the effect is attenuated with increasing gestational weeks, which suggests that elevated uric acid levels in early pregnancy may be a causative factor in preeclampsia. Elevated serum uric acid levels before 20 weeks of gestation are associated with the development of preeclampsia, especially in the early 8-12 weeks of gestation, and the effect attenuates with increasing gestational weeks, which suggest that elevated uric acid in early pregnancy may be a causative factor in preeclampsia.

Diabetes associated with HPV infection in women aged over 50 years: A cross-sectional study from China's largest academic woman's hospital.

Background: Metabolic 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. Methods: We 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. Results: There 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 <5.7%, and the risk ratio for HPV infection in women with diabetes was 1.18 (95%). CI: 1.04-1.33). Sensitivity analysis showed that the risk ratio for HPV infection was 1.47 (95% CL: 1.07-1.91) when diabetes was associated with vaginitis. E-value analysis suggested robustness to unmeasured confounding. Conclusions: Diabetes and prediabetes are at increased risk of coinfection with HPV in female patients aged over 50 years in the cervical clinic.

Reduced serum cholinesterase is an independent risk factor for all-cause mortality in the pediatric intensive care unit.

Objective: Our 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. Methods: We 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. Results: Of 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. Conclusion: After adjusting for inflammation, nutrition, and liver function factors, cholinesterase reduction is still an independent risk factor for pediatric intensive care unit all-cause mortality.