Pregnancy induced hypertension and umbilical cord blood DNA methylation in newborns: an epigenome-wide DNA methylation study.

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.

Development and validation of models for predicting preterm birth and gestational latency following emergency cervical cerclage: A multicenter cohort study.

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.

HDAC5 inactivates CYR61-regulated CD31/mTOR axis to prevent the occurrence of preeclampsia.

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.

Magnetic Resonance Imaging-Based Nomogram to Antenatal Predict Cesarean Delivery for Cephalopelvic Disproportion in Primiparous Women.

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.

LncRNA CRNDE acts as an oncogene in cervical cancer through sponging miR-183 to regulate CCNB1 expression.

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.

Protective effects of apigenin on LPS-induced endometritis via activating Nrf2 signaling pathway.

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-1ß 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.

Roles of Toll-like Receptor 7 and 8 in Prevention of Intrauterine Transmission of Hepatitis B Virus.

BACKGROUND: Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission, but most of the infants born to HBV-positive mothers are protected from infection. However, the mechanisms by which intrauterine transmission is avoided remain elusive, and the roles of toll-like receptors (TLRs) have been proposed. The aims of this study were to clarify if TLR 7 and 8 are involved in the prevention of intrauterine transmission of HBV. METHODS: Real time polymerase-chain reaction (PCR) was used to determine the expression of TLRs and cytokines in placenta and trophoblasts. The expression of MyD88 was interfered with small interfering RNA (siRNA) in trophoblasts. An in intro model mimicking trophoblast barrier was established to evaluate the effect of MyD88 siRNA on HBV transmission across trophoblast barrier. RESULTS: There were significant differences in placental expression of TLR7 (F=3.263, P=0.048) and TLR8 (F=3.257, P=0.048) among control (HBV-negative women), non-infected group (HBV-positive women whose infants were not infected) and infected group (HBV-positive women whose infants were infected). The expression of TLR7 was significantly higher in non-infected group than infected group (P=0.039) and control (P=0.043). There was a significant difference in TLR8 expression between non-infected group and control (P=0.014), and the difference was close to but not significant (P=0.074) between non-infected and infected groups. Exposure of trophoblast to HBV significantly induced the expression of TLR7 (P<0.001), TLR8 (P=0.005), MyD88 (P=0.004), interferon (IFN)-α (P=0.004), IFN-ß (P<0.001) and interleukin (IL)-8 (P=0.001). When MyD88 was interfered by siRNA, the expression of IFN-α (P<0.001), IFN-ß (P=0.01) and IL-8 (P<0.001) was significantly decreased while the amount of HBV transcytosed across trophoblastic barrier significantly increased (P=0.03). CONCLUSIONS: TLR7 and TLR8 on trophoblastic cells play an important role in the prevention of intrauterine HBV transmission by inhibiting HBV translocation across trophoblast.

Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus.

Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human ß-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV.

The molecular feature of abnormal fetal neuromuscular development after maternal use of telbivudine or tenofovir during pregnancy in rodent model.

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 mitochondria/endoplasmic reticulum/lysosome/cytoskeleton, the regulation of arachidonic acid and the development 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.

Injectable rBMSCs-laden hydrogel microspheres loaded with naringin for osteomyelitis treatment.

Osteomyelitis, caused by purulent bacteria invading bone tissue, often occurs in long bones and seriously affects the physical and mental health and working ability of patients; it can even endanger life. However, due to bone cavity structure, osteomyelitis tends to occur inside the bone and thus lacks an effective treatment; anti-inflammatory treatment and repair of bone defects are necessary. Here, we developed injectable hydrogel microspheres loaded with naringin and bone marrow mesenchymal stem cells, which have anti-inflammatory and osteogenic properties. These homogeneous microspheres, ranging from 200 to 1000µm, can be rapidly fabricated using an electro-assisted bio-fabrication method. Interestingly, it was found that microspheres with relatively small diameters (200µm) were more conducive to the initial cell attachment, growth, spread, and later osteogenic differentiation. The developed microspheres can effectively treat tibial osteomyelitis in rats within six weeks, proving their prospects for clinical application.

Exoskeleton Partial-Coated Stem Cells for Infarcted Myocardium Restoring.

The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.

Chondroitin sulfate microspheres anchored with drug-loaded liposomes play a dual antioxidant role in the treatment of osteoarthritis.

Reactive oxygen species (ROS) play a critical role in the pathogenesis of osteoarthritis. The injection of a single antioxidant drug is characterized by low drug utilization and short residence time in the articular cavity, limiting the therapeutic effect of antioxidant drugs on osteoarthritis. Currently, the drug circulation half-life can be extended using delivery vehicles such as liposomes and microspheres, which are widely used to treat diseases. In addition, the composite carriers of liposomes and hydrogel microspheres can combine the advantages of different material forms and show stronger plasticity and flexibility than traditional single carriers, which are expected to become new local drug delivery systems. Chondroitin sulfate, a sulfated glycosaminoglycan commonly found in native cartilage, has good antioxidant properties and degradability and is used to develop an injectable chondroitin sulfate hydrogel by covalent modification with photo-cross-linkable methacryloyl groups (ChsMA). Herein, ChsMA microgels anchored with liquiritin (LQ)-loaded liposomes (ChsMA@Lipo) were developed to delay the progression of osteoarthritis by dual antioxidation. On the one hand, the antioxidant drug LQ wrapped in ChsMA@Lipo microgels exhibits significant sustained-release kinetics due to the double obstruction of the lipid membrane and the hydrogel matrix network. On the other hand, ChsMA can eliminate ROS through degradation into chondroitin sulfate monomers by enzymes in vivo. Therefore, ChsMA@Lipo, as a degradable and dual antioxidant drug delivery platform, is a promising option for osteoarthritis treatment. STATEMENT OF SIGNIFICANCE: Compared with the traditional single carrier, the composite carriers of hydrogel microspheres and liposome can complement the advantages of different materials, which shows stronger plasticity and flexibility, and is expected to become a new and efficient drug delivery system. ChsMA@Lipo not only attenuates IL-1ß-induced ECM degradation in chondrocytes but also inhibits the M1 macrophages polarization and the inflammasome activation. The obtained ChsMA@Lipo alleviates the progression of osteoarthritis in vivo, which is promising for osteoarthritis treatment.

Biodegradable intramedullary nail (BIN) with high-strength bioceramics for bone fracture.

About 10 million fractures occur worldwide each year, of which more than 60% are long bone fractures. It is generally agreed that intramedullary nails have significant advantages in rigid fracture fixation. Metal intramedullary nails (INs) can provide strong support but a stress shielding effect can occur that results in nonunion healing in clinic. Nondegradable metals also need to be removed by a second operation. Could INs be biodegradable and used to overcome this issue? As current degradable biomaterials always suffer from low strength and cannot be used in Ins, herein, we report a novel device consisting of biodegradable IN (BIN) made for the first time with bioceramics. These BINs have an extremely high bending strength and stable internal and external structure. Experiments show that the BINs could not only fix and support the tibial fracture model, but also promote osteogenesis and affect the microenvironment of the bone marrow cavity. Therefore, they could be expected to replace traditional metal IN and become a more effective treatment option for tibial fractures.

Altered gene profile of placenta from women with intrahepatic cholestasis of pregnancy.

OBJECTIVES: To investigate the alterations in gene profile of placenta from pregnant women with intrahepatic cholestasis of pregnancy (ICP) and to enhance the insight of etiology and pathogenesis of ICP. METHODS: Ten pregnant women diagnosed ICP were recruited and 10 healthy pregnant women served as control. Four samples were taken from each placenta and RNA was isolated. Gene expression was analyzed with microarray and real time PCR was used to validate the differentially expressed genes. RESULTS: 392 genes were found differentially expressed. Among these differentially expressed genes, 280 were up-regulated and 112 were down-regulated. These differentially expressed genes involved 20 categories including genes involved in transportation, cell growth, apoptosis and immune response that were putatively participated the pathogenesis of ICP. CONCLUSIONS: 293 differentially expressed genes of 20 categories were found in ICP placenta, suggesting the diversity of gene expression alteration and the complexity of etiology and pathogenesis of ICP.

Lamivudine vs placebo or no treatment in preventing the transmission of hepatitis B virus during pregnancy: a systematic review and meta-analysis.

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, I2=41%), HBeAg seropositivity (RR=0.66, 95% CI 0.36 to 1.19, I2=0%) and HBV DNA seropositivity (RR=0.29, 95% CI 0.18 to 0.4`6, I2=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.

MicroRNAs derived from urinary exosomes act as novel biomarkers in the diagnosis of intrahepatic cholestasis of pregnancy.

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.

Motor development delay in offspring is associated with prenatal telbivudine exposure.

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.

Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome.

OBJECTIVE: Our objective was to evaluate whether polycystic ovarian syndrome (PCOS)-associated infertility is related to alterations of leptin, leptin receptor (Ob-R), and the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signal 3 (SOCS3) system in the ovary. DESIGN AND SETTING: A case-control study was conducted in a university hospital. PATIENTS: Thirty-one infertile PCOS women with oligoovulation plus polycystic ovarian morphology and 79 infertile women with tubal blockage (control) participated in the study. The subjects were stratified according to in vitro fertilization outcomes: successful and failed subgroups. METHODS: Serum and follicular fluid (FF) leptin levels were measured with ELISA. RT-PCR and Western blotting were performed to assess expression of mRNA encoding leptin and Ob-R and proteins of p-STAT3 and SOCS3 in granulosa cells (GCs). RESULTS: Leptin levels in serum and FF of PCOS women were significantly higher than those of control (P < 0.01). There were no significant differences in expression of leptin mRNA and short and long Ob-Rs between PCOS and control (P > 0.05). The p-STAT3 level was decreased in PCOS compared with control (P < 0.01), whereas SOCS3 remained significantly unchanged (P > 0.05). Further analysis showed that serum and FF leptin levels were significantly higher, whereas p-STAT3 in GCs was lower in the failed subgroup of PCOS than those in the successful subgroup of PCOS (P < 0.05). CONCLUSION: Hyperleptinemia and high FF leptin are important pathologies of PCOS with infertility. Lower levels of p-STAT3 in GCs may be related to ovarian leptin resistance and fecundity in PCOS women. Relatively high serum and FF leptin and low p-STAT3 in GCs may account for decreased fertilization, implantation, and pregnancy rates of in vitro fertilization in PCOS women.

Involvement of viperin in prevention of intrauterine transmission of hepatitis B virus.

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.

Serum adiponectin, leptin and soluble leptin receptor in pre-eclampsia.

OBJECTIVES: To delineate the changes in serum levels of adiponectin, leptin and soluble leptin receptor, and in the free leptin index in women with pre-eclampsia. METHODS: Blood samples were collected from 38 pregnant women with pre-eclampsia and 42 normotensive pregnant women as controls. Serum concentrations of adiponectin, leptin and soluble leptin receptor were determined by enzyme-link immunosorbent assay and the free leptin index was calculated as the ratio of serum leptin to soluble leptin receptor for each sample. RESULTS: No significant differences were observed between the groups regarding maternal age, gestational age and body mass index. Women with pre-eclampsia had significantly higher levels of serum adiponectin and leptin, and a higher free leptin index than controls (P<0.01, P<0.001 and P<0.001, respectively). There were no significant differences between the two groups in serum levels of soluble leptin receptor (P>0.05). CONCLUSIONS: The study demonstrated elevated serum levels of adiponectin and leptin as well as a higher free leptin index in women with pre-eclampsia, suggesting these as important factors contributing to this complication of pregnancy.