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.

Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies.

Prenatal cell-free DNA (cfDNA) screening uses extracellular fetal DNA circulating in the peripheral blood of pregnant women to detect prevalent fetal chromosomal anomalies. However, numerous severe conditions with underlying single-gene defects are not included in current prenatal cfDNA screening. In this prospective, multicenter and observational study, pregnant women at elevated risk for fetal genetic conditions were enrolled for a cfDNA screening test based on coordinative allele-aware target enrichment sequencing. This test encompasses the following three of the most frequent pathogenic genetic variations: aneuploidies, microdeletions and monogenic variants. The cfDNA screening results were compared to invasive prenatal or postnatal diagnostic test results for 1,090 qualified participants. The comprehensive cfDNA screening detected a genetic alteration in 135 pregnancies with 98.5% sensitivity and 99.3% specificity relative to standard diagnostics. Of 876 fetuses with suspected structural anomalies on ultrasound examination, comprehensive cfDNA screening identified 55 (56.1%) aneuploidies, 6 (6.1%) microdeletions and 37 (37.8%) single-gene pathogenic variants. The inclusion of targeted monogenic conditions alongside chromosomal aberrations led to a 60.7% increase (from 61 to 98) in the detection rate. Overall, these data provide preliminary evidence that a comprehensive cfDNA screening test can accurately identify fetal pathogenic variants at both the chromosome and single-gene levels in high-risk pregnancies through a noninvasive approach, which has the potential to improve prenatal evaluation of fetal risks for severe genetic conditions arising from heterogenous molecular etiologies. ClinicalTrials.gov registration: ChiCTR2100045739 .

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.

Diagnostic value of dual-fluorescence staining in bacterial vaginosis.

OBJECTIVE: The aim of this study was to investigate the epidemiology of bacterial vaginosis (BV) in Shanghai, China, and to explore the value of a dual-fluorescence staining method in the diagnosis of BV. METHODS: Specimens were collected from women with vaginitis at the Obstetrics and Gynecology Hospital of Fudan University from January 2020 to December 2021, and the proportions of various vaginitis types (such as Candida vaginitis, Trichomonas, and bacterial vaginitis) were analyzed statistically. To explore the diagnostic value of dual-fluorescence staining for BV, we first executed a dual-fluorescence staining method to analyze the vaginal secretions of 265 patients, then confirmed our diagnoses by consulting clinical physicians and by using Nugent scoring of Gram staining. RESULTS: There were 16,905 patients who were diagnosed with vaginitis over the previous 2 years, with a median age of 32 (minimum age of 9 years and maximum of 84 years). Of these patients, we noted 10,887 cases (64.40%) of BV. Our staining results revealed that the dual-fluorescence method was consistent with Gram staining in the diagnosis of BV, with a P value of less than .001 using a χ 2 test and a consistency kappa value of 0.896. Compared with Gram staining, the dual-fluorescence staining method required an acceptable time (2.2 min vs 2.5 min, respectively) and exhibited different visual effects (green and yellow vs purple and red, respectively). CONCLUSION: Dual-fluorescence staining for the detection of bacterial diseases of the vagina exhibited acceptable consistency with Gram staining and performed well with respect to dyeing time, stability, and the interpretation of results. We argue that this method should be used in outpatient services.

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.

Advances in Research on the Relationship between Vaginal Microbiota and Adverse Pregnancy Outcomes and Gynecological Diseases.

The human microbiota inhabiting different parts of the body has been shown to have a significant impact on human health, with the gut microbiota being the most extensively studied in relation to disease. However, the vaginal microbiota is also an essential commensal microbiota in the female body that plays a crucial role in female health. Despite receiving less attention than gut microbiota, its importance in regulating reproductive immunity and its complex dynamic properties have been increasingly recognized in recent years. Advances in research on the relationship between vaginal microbiota and pregnancy outcomes & gynecological diseases in women have shed light on the importance of maintaining a healthy vaginal microbiota. In this review, we aim to compile recent developments in the study of the vaginal microbial ecosystem and its role in female health and reproductive outcomes. We provide a comprehensive account of the normal vaginal microbiota, the association between the vaginal microbiota and pregnancy outcomes, and the impact of the vaginal microbiota on gynecological diseases in women. By reviewing recent research, we hope to contribute to the advancement of academic medicine's understanding of the vaginal microbiota's importance in female health. We also aim to raise awareness among healthcare professionals and the general public of the significance of maintaining a healthy vaginal microbiota for better reproductive health and the prevention of gynecological diseases.

Miltefosine exhibits fungicidal activity through oxidative stress generation and Aif1 activation in Candida albicans.

Invasive candidiasis is the most common and serious fungal disease worldwide, and the development of antifungal drug resistance in Candida spp. is an emerging problem. Miltefosine, approved as an orphan drug for the therapy of invasive candida infections by the US Food and Drug Administration, has broad-spectrum antifungal activity, but its mechanism of action is unclear. This study evaluated the antifungal drug susceptibility of azole-resistant Candida spp. isolates and found that miltefosine showed good activity, with a geometric mean value of 2 µg/mL. Miltefosine was found to increase production of intracellular reactive oxygen species (ROS) and induce apoptosis in Candida albicans. RNA sequencing (RNA-Seq) analysis and iTRAQ-labelling-based quantitative proteomic mass spectrometry analysis were undertaken. Aif1 and the oxidative stress pathway involved in miltefosine-mediated apoptosis were identified using global transcriptomic and proteomic combined screening. Miltefosine increased mRNA and protein expressions of Aif1. The localization of Aif1 was examined using confocal microscopy, and the GFP-Aif1 fusion protein was found to be translocated from the mitochondria to the nucleus when sensing miltefosine. Next, the pex8 Δ/Δ strain was constructed, and the minimum inhibitory concentration of miltefosine was found to decrease four-fold (from 2 to 0.5 µg/mL) and the intracellular ROS increased significantly after knocking out the PEX8 gene. Moreover, miltefosine was found to trigger Hog1 phosphorylation. These findings indicate that Aif1 activation and the Pex8-mediated oxidative stress pathway are the mechanisms of action of miltefosine on C. albicans. The results help to aid understanding of the mechanisms by which miltefosine acts on fungi.

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.

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.

High-Throughput Sequencing-Based Analysis of Changes in the Vaginal Microbiome during the Disease Course of Patients with Bacterial Vaginosis: A Case-Control Study.

Background: The vaginal microbiome is closely associated with the onset and recurrence of bacterial vaginosis (BV). In the present study, the state of vaginal microbiota during the onset and post-treatment asymptomatic stages of BV were compared to that of a healthy population to evaluate the changes in different characteristic bacteria during the onset, progression, and remission of BV. Methods: A case−control study was performed to explore these changes. Women with clinical symptoms of BV were divided into the disease group (M) and case−control group (C) based on the Nugent score. Subjects in the disease group whose symptoms were resolved after the treatment were assigned to the treated group (T) and healthy subjects were recruited into the normal control (N) group. The V3−V4 hypervariable regions of bacterial 16S rRNA genes were sequenced on the Illumina MiSeq platform. Results: The N harbored the highest number of detected species and a higher abundance of microbiota; they had a significantly higher abundance of Lactobacillus and different bacterial community composition compared to the other three groups. In group M, Gardnerella vaginalis was the dominant species, whereas Lactobacillus iners was predominant in the other three groups. While Lactobacillus was more commonly present in Group C compared to group M. it was significantly increased in group T. Alpha diversity analysis of bacterial communities revealed significant differences in community richness and diversity among all four groups (p < 0.05). Significant differences in the distribution of various bacterial communities among the different groups were also observed (p < 0.05). Specifically, the abundance of eight bacterial taxa (Megasphaera, Aerococcus christensenii, Clostridiales, Gardnerella, Peptostreptococcus, Veillonellaceae, Akkermansia, Coriobacteriales) differed significantly among the four groups (p < 0.05). Conclusion: Significant differences in the composition and alpha diversity of the vaginal microbiota at different stages of BV and the distribution of bacterial communities were observed among the investigated groups. In addition to Gardnerella, Sneathia sanguinegens and Prevotella timonensis play an important role in the pathogenesis of BV. The appearance of BV-like clinical symptoms was closely associated with the decrease in Prevotella and Atopobium vaginae populations.

Diabetes associated with cervical carcinoma among high-risk HPV-infected patients with cytologically diagnosed high grade squamous intraepithelial lesion.

Background: Diabetes 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. Methods: We 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. Results: Among HGSIL patients with high-risk HPV infection, compared with women with HbA1c <5.7%, the odds ratio for women with prediabetes was 1.72 (95% CI: 0.87-3.41) and the odds ratio for women with diabetes was 3.29 (95% CI: 1.10-9.80) for cervical cancer. Sensitivity analysis showed that diabetes was significantly associated with cervical cancer in different age groups and different HPV variant. E-value analysis showed robustness to unmeasured confounding. Conclusions: In patients with HR-HPV combined with HGSIL, diabetes and prediabetes are associated with cervical cancer.

Genetic deconvolution of fetal and maternal cell-free DNA in maternal plasma enables next-generation non-invasive prenatal screening.

Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

Admission serum lactate is associated with all-cause mortality in the pediatric intensive care unit.

OBJECTIVE: Our aim was to assess the relationship between serum lactate levels at intensive care unit (ICU) admission and all-cause mortality in the pediatric ICU. METHODS: We used the pediatric intensive care (PIC) database (a large pediatric intensive care database in China from 2010 to 2018) to conduct a retrospective analysis to evaluate the serum lactate levels at ICU admission of 12,213 critically ill children admitted to the ICU. We analyzed the association between serum lactate 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 lactate and all-cause mortality. RESULTS: Of the 12,213 children, 755 (6.18%) died. After fully adjusting for confounding factors, serum lactate was an independent risk factor for all-cause mortality in pediatric ICU (adjusted OR=1.14, 95% CI: 1.12, 1.17). The results of sensitivity analysis showed that in different stratified analyses, the effect of serum lactate on all-cause mortality remained stable. CONCLUSIONS: Admission serum lactate is a risk factor, which is independent of the presence of acid-base disorders, inflammation, malnutrition, and renal or hepatic dysfunction, for all-cause mortality in the pediatric intensive care unit.

Multilocus Sequence Typing and Antifungal Susceptibility of Vaginal and Non-vaginal Candida glabrata Isolates From China.

Candida glabrata is a common cause of Candida infections. In our present study, we investigated the antifungal susceptibility and molecular epidemiology of vaginal and non-vaginal C. glabrata isolates. Seventy-six vaginal C. glabrata strains isolated from patients with vulvovaginal candidiasis and 57 non-vaginal C. glabrata isolates were collected at two hospitals in Shanghai, China. Antifungal susceptibility was examined using a broth microdilution method. Multilocus sequence typing was used for genotyping. Overall, 28 (21.1%), 28 (21.1%), and 29 (21.8%) C. glabrata isolates were resistant to fluconazole, itraconazole, and voriconazole, respectively. Briefly, 18 (23.7%), 18 (23.7%), and 19 (25%) vaginal strains were resistant to fluconazole, itraconazole, and voriconazole. While the resistance to these antifungals were all 17.5% (10/57) in non-vaginal strains. All isolates retained susceptibility to amphotericin B, and only four non-vaginal isolates were caspofungin resistant. Genotyping identified 17 ST patterns. In non-vaginal samples, the same genotypes appear as in the vaginal samples, except for one genotype (ST-182), while in the vaginal samples more genotypes appear (ST8, ST19, ST45, ST55, ST66, ST80, ST138, and ST17). The most common genotype was ST7 (81 strains), followed by ST10 (14 strains) and ST15 (11 strains). The majority of resistant phenotype strains (25/30, 83.3%) correlated to the predominant genotype (ST7), and the rest belonged to ST3 (2/30, 6.7%), ST10 (1/30, 3.3%), ST19 (1/30, 3.3%), and ST45 (1/30, 3.3%). Our survey revealed cross-resistance in vaginal and non-vaginal C. glabrata isolates. Moreover, there is no genotype associated with the resistance phenotype.

Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities in a cohort of 39,580 pregnancies.

The aim of this study was to determine the predictive value of expanded noninvasive prenatal testing (NIPT-plus) for fetal chromosome abnormalities in the second trimester (12-26 weeks). We conducted a retrospective cohort study of 39,580 pregnancies with NIPT-plus. Screening positive cases were diagnosed with karyotyping and single-nucleotide polymorphism array analysis (SNP array)/copy number variation sequencing (CNV-seq) with follow-up. The positive predictive values (PPVs) of trisomy 21, 18, and 13 (T21, T18, and T13), sex chromosome aneuploidies (SCAs), and microdeletion and microduplication syndromes (MMS) by NIPT-plus were recorded. We assessed the predictive value of NIPT-plus based on maternal age and conventional indications. Of 39,580 pregnancies with NIPT-plus, 511 (1.3%) had prenatal screening positive results of fetal chromosome abnormality, of which 87.7% (448/511) had invasive prenatal diagnosis. NIPT-plus performed better in predicting fetal SCAs and chromosome aneuploidies for pregnancies with advanced maternal age (AMA) than young maternal age (YMA). Besides, the PPVs of T21, T13, and chromosome aneuploidies showed an upward trend when comparison was based on maternal age in 5-year subintervals. The termination rates of 45,X, 47,XXX, 47,XXY, and 47,XYY were 100% (11/11), 20.0% (3/15), 91.7% (22/24), and 7.1% (1/14) with postnatal follow-up. Last but not least, the PPV for MMS is 41.7% (30/72), which may have a positive correlation between the size of CNVs. Pregnant women with screen-positive results for common trisomies (T13, T18, and T21) were more willing to conduct invasive prenatal diagnosis compared to those with positive results for SCAs or MMS. However, the current study demonstrated SCAs and MMS had the lowest PPV. This highlights the importance of confirmatory prenatal diagnosis in those patients and the potential impact on genetic counseling and informative decision-making.

Copan Walk Away Specimen Processor (WASP) Automated System for Pathogen Detection in Female Reproductive Tract Specimens.

Objective: Automation is increasingly being applied in clinical laboratories; however, preanalytical processing for microbiology tests and screening is still largely performed using manual methods owing to the complex procedures involved. To promote automation of clinical microbiology laboratories, it is important to assess the performance of automated systems for different specimen types separately. Therefore, the aim of this study was to explore the potential clinical application of the Copan Walk Away Specimen Processor (WASP) automated preanalytical microbiology processing system in the detection of pathogens in female reproductive tract specimens and its feasibility in optimizing diagnostic procedures. Methods: Female reproductive tract specimens collected from pregnant women at their first obstetric check-up were inoculated into culture media using the Copan WASP automated specimen processing system and were also cultured using a conventional manual inoculation method. After 48 h of culture, the growth of colonies was observed, and the types of bacteria, number of colonies, and efficiency in isolating single colonies were compared between the automated and manual groups. The specimens collected from the WASP system using the Copan-ESwab sample collection tubes were further analyzed for the presence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasmaurealyticum (UU) via fluorescence quantitative polymerase chain reaction (qPCR) and an immunochromatographic assay to investigate the feasibility of this method in optimizing detection of these common pathogens of the female reproductive tract. Results: Compared with the manual culture method, the Copan WASP microbiology automation system detected fewer bacterial types (P<0.001) and bacterial colonies (P<0.001) but had a higher detection rate of single colonies (P<0.001). There was no significant difference in the detection rates of common pathogens encountered in clinical obstetrics and gynecology, including group B Streptococcus (GBS) (P=0.575) and Candida (P=0.917), between the two methods. Specimens collected in the Copan-ESwab tubes could be used for screening of GBS and CT via fluorescence-based qPCR but not with immunochromatography. However, UU and NG were not detected in any sample with either method; thus, further validation is required to determine the feasibility of the Copan system for screening these pathogens. Conclusion: The Copan WASP microbiology automation system could facilitate the optimization of diagnostic procedures for detecting common pathogens of the female reproductive system, thereby reducing associated costs.

Characterization of Vaginal Microbiota in Women With Recurrent Spontaneous Abortion That Can Be Modified by Drug Treatment.

Objective: The role of vaginal microbiota in recurrent spontaneous abortion (RSA) remains unknown. The purpose of this study was to investigate characteristics of vaginal microbiota and the effects of drug treatment on vaginal microbiota of patients with RSA. Methods: A case-control study was performed, in which non-pregnant patients who experienced RSA were selected and divided into untreated and drug-treated groups. Drug-treated patients were subdivided into the metformin group, metformin plus aspirin group, and other drugs group. Healthy women who had live births and never experienced spontaneous abortion were enrolled in the control group. Characteristics of vaginal microbiomes of patients with RSA and healthy women and the impact of drug treatment on the microbiome was evaluated via 16S rRNA gene sequencing of the V3-V4 region using the Illumina MiSeq platform. Results: Women who underwent RSA had lower microbial richness than healthy women. Compared to controls, the relative abundance of seven taxa (Megasphaera, Sneathia sanguinegens, Pseudomonas, Sphingomonas, Rhodococcus, Burkholderia- Caballeronia-Paraburkholderia, and Corynebacterium_1) in the patient's vaginal microbiota changed significantly, which may be closely related to RSA. The composition of the vaginal microbial community in RSA patients was altered by drug treatment. Metformin combined with aspirin treatment significantly increased the relative abundance of vaginal Lactobacillus spp. in patients. Conclusion: An altered vaginal microbiome composition might be associated with RSA, which could be modified by drug treatment. The effect of metformin combined with aspirin on vaginal Lactobacillus is worthy of attention.