IntroductionUmbilical artery thrombosis (UAT) is a rare but serious pregnancy complication, potentially causing fetal growth restriction, distress, and stillbirth. Diagnosis relies on Doppler ultrasound and pathological assessment. Close monitoring and potential low-molecular-weight heparin (LMWH) therapy aim to prolong gestation and improve outcomes, but debate persists on its efficacy compared to expectant management.MethodsA retrospective study, conducted between January 2013 and December 2023, enrolled singleton pregnant women diagnosed with UAT during pregnancy. The experiment group included pregnant women who underwent LMWH with anti-coagulation therapy during pregnancy, while the expectant group comprised pregnancies that received standard prenatal care without any specific intervention for UAT.ResultsThe expectant group showed a significant increase in birth weight (expectant vs. experiment: 2434.40 ± 770.20 g vs. 1874.46 ± 717.83 g, P < 0.05) and a significant decrease in the incidence of births before 34 weeks (expectant vs. experiment: 42.24% vs. 82.75%, P < 0.05). Gestational age at birth was notably higher in the expectant group as compared to the experiment group (35.32 ± 3.89 vs. 33.59 ± 4.17), although the difference did not reach statistical significance (p = 0.110). The multi-factor ANOVA revealed statistically significant effects of anti-coagulation therapy (F = 4.479, p = 0.039) and gestational age at birth (F = 179.110, p = 0.000) on birth weight. This study found that the relationship between these variables can be formulated as: birth weight = −3314.782–256.106 × anti-coagulation therapy (coded as 1 if yes and 0 if no) +161.858 × gestational age at birth.ConclusionOur study suggests that expectant therapy may offer substantial benefits compared to experimental therapy involving the administration of LMWH.
In a woman who received cerclage in the previous pregnancy, obstetricians were highly likely to perform this surgery in her subsequent pregnancy. However, many researchers have advocated against the use of repeat cerclage. The objective of this study was to evaluate the effectiveness of repeat cerclage in managing the subsequent pregnancy for participants with a history of cervical cerclage. We retrospectively collected data from patients who had a history of cervical cerclage and received repeat cerclage in the subsequent pregnancy. A self-controlled comparative analysis was undertaken to evaluate the differences in baseline characteristics and pregnancy outcomes between the initial cerclage and the repeat cerclage. A total of 173 patients were included in the study. These patients were divided into two groups, the initial cerclage group and the repeat cerclage group. Consequently, the gestational age at delivery, birth weight, live birth outcome, and neonatal morbidity in the repeat cerclage group were significantly improved compared to the initial cerclage group (p < 0.001 for all aforementioned indicators). All patients were further divided into four subgroups based on their indications for initial cerclage. Specifically, 54 patients received an initial cerclage due to prior history (group A), 45 patients based on ultrasound findings (group B), 63 patients due to physical examination (group C), and 11 participants for inappropriate indications (group D). As a result, repeat cerclage significantly increased both gestational age at delivery and birth weight in group A, group B, and group C, with statistical significance noted as follows: group A (p = 0.007 for gestational age, p = 0.044 for birth weight), group B (p = 0.002 for gestational age, p = 0.011 for birth weight), and group C (p < 0.001 for both) No significant differences were noted in group D. In conclusion, the clinical outcome of repeat cerclage in patients with a prior history of cervical cerclage, regardless of whether it was indicated by history, ultrasound, or physical examination, was found to be significantly beneficial for the patients. For patients who have undergone a prior cerclage based on evidence-supported indications of CI, repeat cerclage may be a prudent consideration.
BACKGROUND:Temporomandibular disorders (TMD) are common, particularly in females of reproductive age, but it remains unclear if TMD and female reproductive traits directly influence each other. Previous studies have suggested links between reproductive factors, such as the menstrual cycle and menopause, and TMD, yet any causal link is unconfirmed. This study seeks to delineate the reciprocal causal interplay between female reproductive traits and TMD. METHODS:A bidirectional Mendelian randomization (MR) approach was applied to assess five reproductive traits-age at menarche, first sexual intercourse, first birth, last birth, and menopause-considering TMD as the outcome in one analysis and the exposure in the reverse. Statistical methods, including the inverse variance-weighted method, MR Egger, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), Cochran's Q test, and leave-one-out analyses, were used to examine pleiotropy and heterogeneity. RESULTS:Later age at first sexual intercourse (odds ratio (OR) = 0.51, 95% confidence intervals (CI) 0.37-0.71, p = 6.46 × 10-5), first birth (OR = 0.86, 95% CI 0.78-0.95, p = 0.003), and last birth (OR = 0.37, 95% CI 0.17-0.78, p = 0.009) were identified to be protective against TMD. No significant associations emerged for age at menarche or menopause. However, TMD onset may contribute to delayed menarche (Beta = 0.04, 95% CI 0.01-0.06, p = 0.035) without affecting other reproductive traits. CONCLUSIONS:Genetically determined later timing of first sexual intercourse, first birth, and last birth may protect against TMD, while TMD onset may delay menarche, suggesting a bidirectional relationship between reproductive timing and TMD.
BACKGROUND:Emergency cesarean delivery (CD) is a risk factor for postpartum infection, but it is not clear whether preoperative vaginal disinfection can reduce the incidence of postoperative infectious diseases. OBJECTIVE:This study evaluates the efficacy of preoperative vaginal preparation in patients undergoing emergency cesarean delivery. METHOD:Seven predominant electronic databases were searched, including four English databases and three Chinese databases, from inception till April 30, 2024. Randomized trials that evaluated vaginal preparation before emergency CD were included in the study. All eligible studies were retrieved and subsequently managed using Note Express, RevMan, and R language. Discrepancies were resolved by group discussion. Outcomes such as postoperative endometritis, fever, wound infection, suspected neonatal sepsis, readmission, and emergency department visits were analyzed. RESULTS:A total of 12 studies were identified in this study, involving 5055 participants, with 3002 patients in the experiment group and 2053 in the control group. In comparison with controls, the experiment group had a significant lower incidence of post-cesarean endometritis (RR = 0.49, 95% confidence interval [CI]: 0.29-0.82, P = 0.007) and a significantly lower incidence of suspected neonatal sepsis (RR = 0.46, 95% CI: 0.34-0.63, P < 0.01). Subgroup analysis showed a significantly lower incidence of endometritis as well as postoperative fever in experiment groups pertaining to both Asia and Africa. CONCLUSION:Preoperative vaginal preparation prior to emergency cesarean delivery can reduce the occurrence of postoperative endometritis, fever, and suspected neonatal sepsis. Further larger multicenter randomized controlled trials should be conducted to confirm our results.
Group B Streptococcus is a bacterium that colonizes in approximately 20% of pregnant women and can be vertically transmitted to newborns, leading to maternal-neonatal adverse outcomes, such as chorioamnionitis, neonatal sepsis, and pneumonia. However, there is currently no agreement on the optimal induction method for this specific population. This study aims to evaluate the safety of a single balloon catheter (BC) in comparison to dinoprostone for labor induction in term pregnant women with group B Streptococcus colonization. In this retrospective cohort study, a total of 321 term pregnancies with positive group B Streptococcus requiring Induction of labor (IOL) were included. Out of these, 80 pregnancies were induced with a single BC, while the remaining 241 were induced with dinoprostone. The study compared the safety outcomes between the 2 groups, specifically focusing on maternal and neonatal adverse events. It is important to note that all women in the study received prophylactic antibiotics. When prophylactic antibiotics were administered, no significant differences were observed in terms of mode of delivery, clinical chorioamnionitis, puerperal infection, fetal distress, neonatal asphyxia, neonatal infection, neonatal sepsis, NICU admission, and neonatal pneumonia between the 2 induction methods (all P > .05). Additionally, there were no reported cases of neonatal group B Streptococcus infection following balloon induction in pregnant women with vaginal GBS colonization. In relation to maternal and neonatal adverse events, the study findings indicated that labor induction using a BC was deemed safe for women who were colonized with group B Streptococcus, provided that prophylactic antibiotics were administered either at the onset of labor or when the membranes ruptured.
OBJECTIVIES:Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother.METHODS:Whole-genome bisulfite sequencing (WGBS) was used to examine the changes in whole genome DNA methylation in the umbilical cord blood of three healthy (NC) and four PIH individuals. Using methylKit, we discovered Hypo- and hyper- differentially methylated probes (DMPs) or methylated regions (DMRs) in the PIH patients' cord blood DNA. Pathway enrichments were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays. DMPs or DMRs relevant to the immunological, neurological, and circulatory systems were also employed for enrichment assay, Metascape analysis and PPI network analysis.RESULTS:520 hyper- and 224 hypo-DMPs, and 374 hyper- and 186 hypo-DMRs between NC and PIH group, respectively. Both DMPs and DMRs have enhanced pathways for cardiovascular, neurological system, and immune system development. Further investigation of DMPs or DMRs related to immunological, neurological, and circulatory system development revealed that TBK1 served as a hub gene for all three developmental pathways.CONCLUSION:PIH-associated DMPs or DMRs in umbilical cord blood DNA may play a role in immunological, neurological, and circulatory system development. Abnormal DNA methylation in the immune system may also contribute to the development of CVDs and neurodevelopment disorders.
Aims: Maternal treatment with nucleoside analogues such as telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) has been applied worldwide. However, administration of LdT or TDF during pregnancy may affect the fetal neuromuscular development. We conducted the current study to investigate the histological pathology and transcriptomic changes pertaining to the neuromuscular system of the newborn exposed to LdT or TDF during pregnancy in rodent model. Main methods: Pregnant C57/BL6 mice were randomly divided into three arms and administered either with LdT solution (0.1 ml, 78 mg/kg/d), TDF solution (0.1 ml, 39 mg/kg/d) or normal saline solution (0.1 ml). Pups in each arm were weighed and sacrificed after birth. Both sides of quadriceps femoris muscle of the newborn were obtained. The histological observation was conducted under light microscope. The transcriptional profiling was analyzed with RNA sequencing (RNA seq). Key findings: Four types of morphological abnormalities of the newborn neuromuscular system, being clusters of rhabdomyoblasts, skeletal muscle fibrosis, rhabdomyolysis and necrosis and immature muscle fiber bundles, were noted in both LdT group and TDF group. Moreover, both groups showed significantly decreased gross cross-sectional area of muscle fiber and significantly increased percentage of muscle lesion area. RNA seq identified a total of 164 differentially expressed genes (DEGs) essential to fetal neuromuscular development. These DEGs were involved in calcium regulation, phospholipid activity, muscle cell development, the functioning of mito-chondria/endoplasmic reticulum/lysosome/cytoskeleton, the regulation of arachidonic acid and the develop-ment of nervous system. Significance: Our findings suggest maternal administration of LdT or TDF lead to abnormal neuromuscular development in offspring mice. Further study should be encouraged to investigate the down-stream signaling pathways.
INTRODUCTION:Emergency cervical cerclage is a recognized method for preventing mid-trimester pregnancy loss and premature birth; however, its benefits remain controversial. This study aimed to establish preoperative models predicting preterm birth and gestational latency following emergency cervical cerclage in singleton pregnant patients with a high risk of preterm birth. MATERIAL AND METHODS:We retrospectively reviewed data from patients who received emergency cerclage between 2015 and 2023 in three institutions. Patients were grouped into a derivation cohort (n = 141) and an independent validation cohort (n = 61). Univariate and multivariate logistic and Cox regression analyses were used to identify independent predictive variables and establish the models. Harrell's C-index, time-dependent receiver operating characteristic curves and areas under the curves, calibration curve, and decision curve analyses were performed to assess the models. RESULTS:The models incorporated gestational weeks at cerclage placement, history of prior second-trimester loss and/or preterm birth, cervical dilation, and preoperative C-reactive protein level. The C-index of the model for predicting preterm birth before 28 weeks was 0.87 (95% CI: 0.82-0.93) in the derivation cohort and 0.82 (95% CI: 0.71-0.92) in the independent validation cohort; The C-index of the model for predicting gestational latency was 0.70 (95% CI: 0.66-0.75) and 0.78 (95% CI: 0.71-0.84), respectively. In the derivation set, the areas under the curves were 0.84, 0.81, and 0.84 for predicting 1-, 3- and 5-week pregnancy prolongation, respectively. The corresponding values for the external validation were 0.78, 0.78, and 0.79, respectively. Calibration curves showed a good homogeneity between the observed and predicted ongoing pregnant probabilities. Decision curve analyses revealed satisfactory clinical usefulness. CONCLUSIONS:These novel models provide reliable and valuable prognostic predictions for patients undergoing emergency cerclage. The models can assist clinicians and patients in making personalized clinical decisions before opting for the cervical cerclage.
Background Cephalopelvic disproportion (CPD)-related obstructed labor is associated with maternal and neonatal morbidity and mortality. Accurate prediction of whether a primiparous woman is at high risk of an unplanned cesarean delivery would be a major advance in obstetrics. Purpose To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on MRI findings. Study Type Prospective. Population A total of 150 primiparous women with clinical findings suggestive of CPD. Field Strength/Sequence T1-weighted fast spin-echo sequences, single-shot fast spin-echo (SSFSE) T2-weighted sequences at 1.5 T. Assessment Pelvimetry and fetal biometry were assessed independently by two radiologists. A nomogram model combined that the clinical and MRI characteristics was constructed. Statistical Tests Univariable and multivariable logistic regression analyses were applied to select independent variables. Receiver operating characteristic (ROC) analysis was performed, and the discrimination of the model was assessed by the area under the curve (AUC). Calibration was assessed by calibration plots. Decision curve analysis was applied to evaluate the net clinical benefit. A P value below 0.05 was considered to be statistically significant. Results In multivariable modeling, the maternal body mass index (BMI) before delivery, bilateral femoral head distance, obstetric conjugate, fetal head circumference, and fetal abdominal circumference was significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.838 (95% confidence interval [CI]: 0.774-0.902). The sensitivity and specificity of the nomogram model were 0.787 and 0.764, and the positive predictive and negative predictive values were 0.696 and 0.840, respectively. The model demonstrated satisfactory calibration (calibration slope = 0.945). Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included. Data Conclusion Our study might provide a nomogram model that could identify primiparous women at risk of cesarean delivery caused by CPD based on MRI measurements. Evidence Level 2 Technical Efficacy Stage 2
Advanced abdominal pregnancy is a kind of rare but life-threatening ectopic pregnancy, in addition to maternal and foetal safety until the birth, the placenta management after the foetus is out, is another challenge to obstetricians. Here we presented a 33-week primary advanced abdominal pregnancy case; the patient in this case experienced a laparotomy, which showed placenta adhesion to abdominal viscera, so the placenta was left in situ . Methotrexate was used to accelerate the degradation of the placenta, however, severe intra-abdominal infection and myelosuppression emerged soon, which had never been reported in similar published cases. It is still controversial whether methotrexate should be used for placenta management in advanced abdominal pregnancy, and the dose and frequency of this drug as well as patients’ condition should be comprehensively evaluated when methotrexate therapy is considered.
Objective: To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on the findings of magnetic resonance imaging (MRI) studies. Design: Observational study Setting: University teaching hospital. Population: 168 primiparous women with clinical findings suggestive of cephalopelvic disproportion. Methods: All women underwent MRI measurements prior to the onset of labor. A nomogram model to predict the risk of cesarean delivery was proposed based on the MRI data. The discrimination of the model was calculated by the area under the receiver operating characteristic curve (AUC) and calibration was assessed by calibration plots. The decision curve analysis was applied to evaluate the net clinical benefit. Main Outcome Measures: Cesarean delivery. Results: A total of 88 (58.7%) women achieved vaginal delivery, and 62 (41.3%) required cesarean section caused by obstructed labor. In multivariable modeling, the maternal body mass index before delivery, induction of labor, bilateral femoral head distance, obstetric conjugate, fetal head circumference and fetal abdominal circumference were significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.845 (95% CI: 0.783-0.908; P < 0.001). The sensitivity and specificity of the nomogram model were 0.918 and 0.629, respectively. The model demonstrated satisfactory calibration. Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included. Conclusion: Our study provides a nomogram model that can accurately identify primiparous women at risk of cesarean delivery caused by cephalopelvic disproportion based on the MRI measurements.
Our study was to pinpoint the significance of histone deacetylase 5 (HDAC5) affecting the pathogenesis of preeclampsia (PE) via CD31/mammalian target of rapamycin (mTOR) axis by regulating cysteine-rich angiogenic inducer 61 (CYR61). Expression of HDAC5, CYR61, and CD31/mTOR in placental tissues of patients with PE and trophoblast cells HTR-8/SVneo cells was determined first followed by their interaction analysis. Following different transfection, the significance of HDAC5 in cell functions was assayed in relation to CYR61 and CD31/mTOR. An in vivo PE mouse model was constructed for further validation. The clinical tissue and in vitro cell experimentations discovered that HDAC5 was downregulated in placental tissues of PE patients and trophoblast cells, while CYR61, CD31, mTOR, and p-mTOR displayed upregulation. After overexpression of HDAC5, trophoblast cell functions were enhanced. HDAC5 reduced the acetylation enrichment of H3K27 to inhibit the expression of CYR61. Furthermore, CYR61 promoted the activation of CD31/mTOR axis, thereby inhibiting HTR-8/SVneo cell functions. The in vivo rat model confirmed the above alterations. Taken together, HDAC5 contributes to downregulation of CYR61 through histone deacetylation, inactivating CD31/mTOR axis, which prevents the occurrence and development of PE.
The aim of our study was to compare the efficacy of two dosages of hepatitis B immunoglobulin (HBIG) combined with HBV vaccine (HBVac) to prevent mother-to-child transmission (MTCT) of hepatitis B in HBsAg- and HBeAg-positive mother. We enrolled 331 mother-infant pairs with HBsAg- and HBeAg-positive maternal state from the Women's Hospital School of Medicine of Zhejiang University. Newborns were randomly distributed into two groups according to the dosages of HBIG injection: 100 IU and 200 IU. Newborns from both groups were injected with HBVac in the same doses. We compared the immune outcomes between the two groups and explore the influencing factors of immune outcomes through regression analysis. There was no statistically significant relationship between HBsAg serological transmission of newborns and dosages of HBIG in HBsAg- and HBeAg-positive mother (p > .05). The Logistic regression showed that high DNA load is a risk factor for passive-active immunoprophylaxis failure for both 100 IU and 200 IU group, but higher-dosage HBIG is not necessary for higher-viral-load pregnant women with HBsAg- and HBeAg-positive. In conclusion, combined application of HBVac and a single dose of 100 IU HBIG can achieve the ideal MTCT interruption results for HBsAg- and HBeAg-positive pregnant women.IMPACT STATEMENT What is already known on this subject? Passive-active immunoprophylaxis is proved to be effective in preventing mother-to-child transmission of hepatitis B. Hepatitis B vaccine combined with 100 IU or 200 IU immunoglobulin is mostly recommended in China. What do the results of this study add? At present, there is still a lack scientific basis for improving existing strategies and measures to prevent mother-to-child transmission of hepatitis B in China. What are the implications of these findings for clinical practice and/or further research? 100 IU and 200 IU immunoglobulin show equivalent blocking effect, and combined use of hepatitis B vaccine and 100 IU immunoglobulin is more cost-effective.
Studies have identified a series of lncRNAs that contributed to various tumors, although the underlying mechanisms remain largely unclear. We proposed a ceRNA network and investigate relations among lncRNA/miRNA/mRNA in cervical cancer (CC). The genes of differential expression and lncRNA/miRNA/mRNA network were identified by combining TCGA, miRcode, starBase, miRTarBase, miRDB, TargetScan and STRING databases. Meanwhile, the function enrichment was recognized with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Quantitative real time-PCR (qRT-PCR) was performed to determine colorectal neoplasia differentially expressed (CRNDE) expression in CC tissues and cell lines. The effects of CRNDE on the CC biological functions and cyclin B1 (CCNB1) expression were detected by conducting in vitro and in vivo experiments. Quantitative real time-PCR, western blot and dual-luciferase reporter assay were used to predict the target of miR-183. Furthermore, rescue experiments were conducted to further confirm the regulation of CCNB1 by CRNDE. Systematic analyses of bioinformatics from several databases predicted that CRNDE, miR-183 and CCNB1 were in the same network path. Their expressions were up-regulated in CC tissues and cells. Silencing CRNDE-inhibited cell proliferation, migration and invasion, restricted solid tumor growth and promoted cell apoptosis. Moreover, our results suggested that miR-183 targeted the CCNB1 3'UTR and regulated its expression. Additionally, miR-183 mimic could inverse the antitumor function of CRNDE inhibition and partially eliminated the attenuated expression of CCNB1 induced by silencing CRNDE, indicating that CRNDE could positively regulate CCNB1 expression by sponging miR-183. Our study highlighted a role for the CRNDE/miR-183/CCNB1-axis in CC and offered a promising diagnostic strategy for CC treatment.
自身免疫性肝炎(AIH)的发生率极低,妊娠合并AIH临床罕见。妊娠前诊断的AIH孕妇,通过妊娠期严密监测及规范治疗,可维持病情稳定甚至病情缓解;但妊娠期首次发病的AIH孕妇,由于鉴别诊断困难,易延误治疗导致疾病加重,出现严重的不良母儿结局的风险升高,及时、正确地诊断及治疗可明显改善母儿预后。本例妊娠合并AIH孕妇于2017年在浙江大学医学院附属妇产科医院收治,其妊娠中期出现了明显的肝功能损害,伴黄疸,但无皮肤瘙痒、无明显消化道症状,实验室检查发现循环自身抗体阳性,考虑妊娠合并AIH,予降胆酸、保护肝功能治疗效果欠佳,采用激素治疗效果良好,行剖宫产术分娩一男婴。出院后随访至今,孕妇病情持续缓解,幼儿发育未见异常。
Background: Hepatitis B virus (HBV) infection is a severe health problem, especially in developing countries. Almost 45% of the population lives in highly endemic areas, where the most common form of transmission is mother to child transmission (MTCT). Administration of antiviral therapy has been established. Nevertheless, its efficacy still remains controversial. Methods: We conducted the current study to fully evaluate the effectiveness of lamivudine in preventing the MTCT of HBV based on randomized controlled trials (RCTs). Four English electronic databases and four Chinese electronic databases were searched from the inception of each database to 26 September 2017. Studies were included if they (1) were human RCT studies, (2) indicated exposure to lamivudine, (3) explicitly indicated control to placebo or no treatment, (4) indicated the participants were pregnant women infected with HBVand (5) compared the outcome of interest as the MTCT. Extracted data were tabulated and analyzed using Review Manager. Results: Eleven RCTs were included and analyzed. Compared with controls (placebo or no treatment), lamivudine significantly reduced the probability of MTCT, as indicated by newborn HBsAg seropositivity (RR=0.44, 95% CI 0.26 to 0.74, I-2=41%), HBeAg seropositivity (RR=0.66, 95% CI 0.36 to 1.19, I-2=0%) and HBV DNA seropositivity (RR=0.29, 95% CI 0.18 to 0.4'6, I-2=0%) within 24 h after birth. Similar results were noted pertaining to infant HBsAg seropositivity and HBV DNA seropositivity within 6-7 and 12 mo. Conclusions: Lamivudine can significantly reduce the MTCT of HBsAg and HBV DNA of neonates during the third trimester of pregnancy without severe adverse events.
We aimed to investigate the value of cholestasis-related miRNAs in the diagnosis of intra-hepatic cholestasis of pregnancy (ICP) as well as the molecular mechanisms underlying the role of these miRNAs in the pathogenesis of ICP. In this study, electron microscopy was utilized to observe the exosomes present in the urine samples collected from both ICP patients and healthy pregnant women. Real-time PCR and area under curve (AUC) analysis were performed to predict the values of several miRNAs in the diagnosis of ICP. Bioinformatics analysis and luciferase assays were conducted to identify the target genes of miR-21, miR-29a and miR-590-3p, whose regulatory relationships were then established using real-time PCR, immunohistochemistry (IHC) assay and Western Blot. In the exosomes isolated from urine samples, several miRNAs, including miR-21, miR-29a and miR-590-3p, were differentially expressed between ICP patients and healthy pregnant women. In addition, the gene of intercellular adhesion molecule 1 (ICAM1) was identified as a shared target of miR-21, miR-29a and miR-590-3p, all of which inhibited ICAM1 expression. Therefore, up-regulated expression of miR-21, miR-29a and miR-590-3p in urinary exosomes reduced the expression of ICAM1, which in turn increased the incidence of ICP.
Endometritis is a puzzling disease that often associates with severe pelvic pain. In this study, we aimed to detect whether apigenin had protective effect against LPS-induced endometritis, if so, the underlying mechanism was further investigated. Apigenin was administrated 1 h before LPS treatment. The levels of inflammatory cytokines were measured by ELISA. The expression of NF-κB and Nrf2 were detected by Western blot analysis. The results showed that LPS treatment induced severe histological alteration of uterus and this change was attenuated by the treatment of apigenin. Apigenin significantly attenuated LPS-induced MPO activity, MDA content, and inflammatory cytokines TNF-α and IL-1β production. LPS-induced NF-κB activation was suppressed by apigenin. Furthermore, apigenin elevated the expression of Nrf2 and HO-1 in uterine tissues. In conclusion, the present study demonstrated that apigenin protected against LPS-induced endometritis through activation of Nrf2 signaling pathway and inhibition of NF-κB signaling pathway.
Telbivudine is an orally nucleoside analog with potent and specific antihepatitis B virus (HBV) activity, and it has been reported to block mother-to-infant transmission. However, few studies have focused on the safety of prenatal exposure for offspring development. This is a prospective noninterventional study. Participants were enrolled during delivery through the Women's Hospital of Zhejiang University School of Medicine between January 2012 and September 2013. Neonate's umbilical cord arterial blood (UCAB) was collected after delivery. Hepatitis B virus DNA copy, HBV serology, alanine aminotransferase (ALT), creatine kinase (CK), creatinine (CRE), and blood urea nitrogen (BUN) were measured. The development of the offspring was evaluated by the Chinese Revision of Bayley Scales of Child Development (BSCD-CR) at 12 to 24 months old. Around 30 and 31 chronic hepatitis B mothers were recruited in untreated group (non-LdT group) and telbivudine-treatment group (LdT group), respectively, and 2 children (one in non-LdT group and 1 in LdT group) were lost in follow-up. Sixty-one normal women and their children were recruited as a normal control (control group). Compared with non-LdT group, telbivudine treatment effectively blocks HBV transmission from mother to infant. However, CK in UCAB was significantly increased in the LdT group. Moreover, children with prenatal telbivudine exposure showed lower level of serum creatinine than non-LdT group, reduction of psychomotor developmental index and increased risk of motor development delay. Prenatal telbivudine exposure is correlated with motor development delay in offspring.
The aim of this study was to explore the role of viperin in the prevention of intrauterine infection of hepatitis B virus (HBV). Placental samples were collected from seven HBV-positive pregnant women with their infants infected via intrauterine transmission (infected group), 30 HBV-positive women with non-infected infants (non-infected group), and 30 HBV-negative women (controls). The expression of viperin in placenta was analyzed with immunohistochemistry and Western blotting. The expression of viperin of placental trophoblast cell line Swan71 was determined after exposed to HBV. Viperin was localized to syncytiotrophoblast, and there was a significant difference in placental viperin levels among control, non-infected group and infected group (F = 12.824, p < 0.001). The expression of viperin was significantly higher in non-infected group than in control (p = 0.019) and in infected group (p < 0.001), and viperin expression was significantly lower in infected group than in control (p = 0.001). The exposure to HBV significantly increased the expression of viperin in Swan 71 (p < 0.001). Exposure to HBV up-regulates viperin expression in vivo and in vitro in placental trophoblast, and lack of this up-regulation is associated with intrauterine transmission of HBV.