Perinatal outcomes associated with ICP in twin pregnancies were worse than singletons: an almost 5-year retrospective cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes leading to high perinatal morbidity and mortality. However, few studies have examined twin pregnancies complicated by ICP. To assess the perinatal outcomes of twin pregnancies with ICP, a retrospective cohort study was conducted. METHODS: A total of 633 twin pregnancies and 1267 singleton pregnancies with ICP were included. In addition, a correlation study was performed on the matched total bile acid (TBA) levels from maternal serum, fetal umbilical venous blood, and amniotic fluid of 33 twin pregnancies from twin groups. RESULTS: When compared to singletons, twin pregnancies with ICP had a higher risk of cesarean section (CS) (96.4% vs. 76.1%), preterm birth (PTB) (82.6% vs. 19.7%), fetal distress (2.0% vs. 1.3%), and neonatal intensive care unit (NICU) admission (23.6% vs. 5.1%), which was significantly related to increasing TBA levels (P < 0.05). In twin pregnancies with TBA ≥100 µmol/L, the incidences of CS, PTB, fetal distress, neonatal asphyxia, and meconium-stained amniotic fluid were 94.4, 100, 11.1, 5.6, and 36.1%, respectively. Furthermore, the maximum maternal TBA levels were positively correlated with TBA levels in the amniotic fluid (r = 0.61, P < 0.05) and umbilical cord blood (r = 0.44, P < 0.05), and a similar correlation was found for maternal TBA levels at delivery. TBA levels in umbilical cord blood and amniotic fluid also had a significant and positive correlation (r = 0.52, P < 0.05). CONCLUSIONS: Twin pregnancies with ICP had a higher risk for adverse perinatal outcomes than singletons, which was associated with higher TBA levels. TBA can be transported through the placenta and is involved in uterus-placenta-fetal circulation.

Comparison of transvaginal cervical cerclage versus laparoscopic abdominal cervical cerclage in cervical insufficiency: a retrospective study from a single centre.

BACKGROUND: Cervical cerclage has been proposed as an effective treatment for cervical insufficiency, but there has been controversy regarding the surgical options of cervical cerclage in singleton and twin pregnancies. This study aimed to compare the pregnancy outcomes between transvaginal cervical cerclage (TVC) and laparoscopic abdominal cervical cerclage (LAC) in patients with cervical insufficiency. We also aimed to evaluate the efficacy and safety, and provide more evidence to support the application of cervical cerclage in twin pregnancies. METHODS: A retrospective study was carried out from January 2015 to December 2021. The primary outcomes were the incidence of spontaneous preterm birth (sPTB) < 24 weeks, < 28, < 32, < 34 weeks, and < 37weeks, gestational age at delivery, and the incidence of admission for threatened abortion or preterm birth after cervical cerclage. The secondary outcomes included admission to the Neonatal Intensive Care Unit, adverse neonatal outcomes and neonatal death. We also analysed the pregnancy outcomes of twin pregnancies after cervical cerclage. RESULTS: A total of 289 patients were identified as eligible for inclusion. The LAC group (n = 56) had a very low incidence of sPTB ˂ 34 weeks, and it was associated with a significant decrease in sPTB < 28 weeks, ˂32 weeks, ˂34 and < 37 weeks, and admission to the hospital during pregnancy for threatened abortion or preterm birth after cervical cerclage (0 vs.27%; 1.8% vs. 40.3%; 7.1% vs. 46.8%; 14% vs. 63.5%, 8.9% vs. 62.2%, respectively; P < 0.001), and high in gestational age at delivery compared with the TVC group (n = 233) (38.3 weeks vs.34.4 weeks,P < 0.001). Neonatal outcomes in the LAC group were significantly better than those in the TVC group. The mean gestational age at delivery was 34.3 ± 1.8 weeks, with a total foetal survival rate of 100% without serious neonatal complications in twin pregnancies with LAC. CONCLUSION: In patients with cervical insufficiency, LAC appears to have better pregnancy outcomes than TVC. For some patients, LAC is a recommended option and may be selected as the first choice. Even in twin pregnancies, cervical cerclage can improve pregnancy outcomes with a longer latency period, especially in the LAC group.

Corrigendum to "Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway" [J Ginseng Res 46 (2022) 156-166].

[This corrects the article DOI: 10.1016/j.jgr.2021.05.011.].

Pregnancy maternal fetal outcomes among pregnancies complicated with atrioventricular block.

BACKGROUND: Atrioventricular block (AVB) during pregnancy is rare. Case study for pregnancy with AVB have been reported but a consensus guideline for peripartum management has not been established. This study aimed to investigate cardiac and obstetric complications and outcomes in our pregnant women with AVB and share our management experience. METHODS: This was a retrospective study. We reviewed a total of 74 pregnant women with AVB who delivered at our tertiary care center in the past 10 years. The patients were categorized into four groups according to the degree of block. The data were analyzed and compared among the four groups of patients. RESULTS: Regarding the cardiac complications, the cardiac function level showed significant difference among patient groups. The higher NYHA class were observed in patients with higher degree AVB. Pacemaker was placed before delivery in 32/33 patients with III° AVB, 8/25 patients with II° AVB, and 0/16 patient with I° AVB. Other types of arrhythmias except AVB were present in all groups of patients but more frequently observed in type I patients with II° AVB. No other heart abnormalities were observed among the patient groups. Obstetric complications were found in 21 women (28.4%), including premature labor, premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), preeclampsia, etc. The incidence rate of fetal cardiac abnormalities was 6.58%. But no statistical difference was detected among four groups of patients for fetal and maternal complications and fetal cardiac abnormalities (P>0.05). Caesarean section was performed more in patients with high-degree AVB than in patients with low-degree AVB. No maternal or neonatal death in our cases. CONCLUSIONS: Most women with AVB could achieve successful pregnancy and delivery. Patients with II° AVB type II and III° AVB should be monitored vigilantly during pregnancy and post-partum. Temporary pacing before delivery appeared to be beneficial for women with III°AVB, and accurate diagnosis and care by a multidisciplinary team was recommended.

Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway.

BACKGROUND: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. METHODS: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. RESULTS: P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1ß. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1ß. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. CONCLUSION: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Piceatannol protects against sepsis-induced myocardial dysfunction via direct inhibition of JAK2.

Sepsis-induced myocardial dysfunction (SIMD) represents one of the serious complications secondary to sepsis, which is a leading cause of the high mortality rate among septic cases. Subsequent cardiomyocyte apoptosis, together with the uncontrolled inflammatory response, has been suggested to be closely related to SIMD. Piceatannol (PIC) is verified with potent anti-apoptotic and anti-inflammatory effects, but its function and molecular mechanism in SIMD remain unknown so far. This study aimed to explore the potential role and mechanism of action of PIC in resisting SIMD. The interaction of PIC with JAK2 proteins was evaluated by molecular docking, molecular dynamics (MD) simulation and surface plasmon resonance imaging (SPRi). The cecal ligation and puncture-induced septicemia mice and the LPS-stimulated H9C2 cardiomyocytes were prepared as the models in vivo and in vitro, separately. Molecular docking showed that JAK2-PIC complex had the -8.279 kcal/mol binding energy. MD simulations showed that JAK2-PIC binding was stable. SPRi analysis also showed that PIC has a strong binding affinity to JAK2. PIC treatment significantly ameliorated the cardiac function, attenuated the sepsis-induced myocardial loss, and suppressed the myocardial inflammatory responses both in vivo and in vitro. Further detection revealed that PIC inhibited the activation of the JAK2/STAT3 signaling, which was tightly associated with apoptosis and inflammation. Importantly, pre-incubation with a JAK2 inhibitor (AG490) partially blocked the cardioprotective effects of PIC. Collectively, the findings demonstrated that PIC restored the impaired cardiac function by attenuating the sepsis-induced apoptosis and inflammation via suppressing the JAK2/STAT3 pathway both in septic mice and H9C2 cardiomyocytes.

Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts.

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10-5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis.

Intrafetal laser therapy in a monochorionic diamniotic triplet pregnancy with two acardiac fetuses: a case report and literature review.

BACKGROUND: Monochorionic diamniotic triplet pregnancies are rare. Twin reversed arterial perfusion sequence in monochorionic triplet pregnancies is extremely rare, and it is associated with high perinatal morbidity and mortality rates in the "pump fetus." CASE PRESENTATION: We reported a case of monochorionic diamniotic triplet pregnancy with twin reversed arterial perfusion sequence, including two acardiac fetuses sharing a single amniotic sac and a normal fetus in another amniotic sac. Due to rapid growth of the acardiac fetuses, intrafetal laser therapy was performed in both of them under ultrasound guidance at 15 weeks +5 days. Subsequently, regular and careful antenatal care including fetal ultrasonography and doppler and fetal echocardiography was conducted. At 37 weeks +4 days, a healthy female baby weighing 2510 g was delivered. The baby was followed up and now at 11 months old is in good health. CONCLUSIONS: Twin reversed arterial perfusion sequence in monochorionic triplet pregnancy should be diagnosed early by ultrasound imaging during pregnancy. Individualized management should be based on clinical conditions to improve the perinatal outcome of the pump twin. Intrafetal laser therapy could be an alternative procedure when intrauterine intervention is required.

Successful pregnancy and live birth in woman with congenital adrenal hyperplasia: A case report.

RATIONALE: Women with congenital adrenal hyperplasia (CAH) can suffer from impaired fertility rates as a result of increased androgen secretion or impaired sex steroid production. CAH patients have lower pregnancy rate compared to normal women. Only a few cases with successful pregnancy have been reported in the literature. This report described a case of CAH with successful pregnancy and live birth. PATIENT CONCERNS: A 23-year-old woman visited our endocrinology department for clitoral hypertrophy and primary amenorrhea. DIAGNOSES: The patient was diagnosed as CAH. INTERVENTION: Prednisone was initially started to improve the patient's symptoms. Then she underwent clitoral resection and vaginoplasty several months later. She continuously took the prednisolone after the operation and had been undergoing regular checkups. OUTCOMES: She was pregnant spontaneously without assisted reproductive technology and had a successful live birth. Her baby had shown normal external genitalia with normal karyotype and normal development up to 6 years of age. LESSONS: Some mild CAH patients with certain types can achieved successful pregnancy without any assisted reproductive technology after treatment with steroid. The pregnancy rate among CAH women who wish to conceive may be much more optimistic than previous researches.

Disrupted compensatory response mediated by Wolfram syndrome 1 protein and corticotrophin-releasing hormone family peptides in early-onset intrahepatic cholestasis pregnancy.

INTRODUCTION: The most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress. METHODS: A total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation. RESULTS: Placental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group. DISCUSSION: Our study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.

All-Trans-Retinoic Acid Suppresses Neointimal Hyperplasia and Inhibits Vascular Smooth Muscle Cell Proliferation and Migration via Activation of AMPK Signaling Pathway.

The proliferation and migration of vascular smooth muscle cells (VSMC) is extensively involved in pathogenesis of neointimal hyperplasia. All-trans-retinoic acid (ATRA) is a natural metabolite of vitamin A. Here, we investigated the involvement of AMP-activated protein kinase (AMPK) in the anti-neointimal hyperplasia effects of ATRA. We found that treatment with ATRA significantly reduced neointimal hyperplasia in the left common carotid artery ligation mouse model. ATRA reduced the proliferation and migration of VSMC, A7r5 and HASMC cell lines. Our results also demonstrated that ATRA altered the expression of proliferation-related proteins, including CyclinD1, CyclinD3, CyclinA2, CDK2, CDK4, and CDK6 in VSMC. ATRA dose-dependently enhanced the phosphorylation level of AMPKα (Thr172) in the left common carotid artery of experimental mice. Also, the phosphorylation level of AMPKα in A7r5 and HASMC was significantly increased. In addition, ATRA dose-dependently reduced the phosphorylation levels of mTOR and mTOR target proteins p70 S6 kinase (p70S6K) and 4E-binding protein 1 (4EBP1) in A7r5 and HASMC. Notably, the inhibition of AMPKα by AMPK inhibitor (compound C) negated the protective effect of ATRA on VSMC proliferation in A7r5. Also, knockdown of AMPKα by siRNA partly abolished the anti-proliferative and anti-migratory effects of ATRA in HASMC. Molecular docking analysis showed that ATRA could dock to the agonist binding site of AMPK, and the binding energy between AMPK and ATRA was -7.91 kcal/mol. Molecular dynamics simulations showed that the binding of AMPK-ATRA was stable. These data demonstrated that ATRA might inhibit neointimal hyperplasia and suppress VSMC proliferation and migration by direct activation of AMPK and inhibition of mTOR signaling.

A new surgical technique "cervical internal os plasty" in cesarean delivery for placenta previa accreta: A case-control study.

Placenta previa accreta is an obstetrical complication that severely affects the heath of the fetus and the mother due to massive hemorrhage during pregnancy. This study reported a new suture technique called "cervical internal os plasty" to control obstetrical hemorrhage in cesarean delivery for patients with placenta previa accreta and retrospectively evaluated the safety and effectiveness of the new technique.From January 2012 to May 2018, we collected 56 patients with this new suture technique, which repaired the damaged weak area with bleeding from the placental attachment site in the lower uterine segment, and restored the damaged anatomic internal os of the cervix. Meanwhile, we compared it with 60 cases with other conservative methods described by other obstetricians with the same qualifications. The perioperative outcomes (blood loss, blood transfusion, operative time, other applied medical technology, and so on) between the 2 groups were recorded in this report.There were no significant differences between 2 groups among age, gravidity, parity, gestational age, and previous dilatation and curettage techniques (P > .05). Of the patients with placenta previa accrete, 77.6% (90/116) had previous dilatation and curettage. The comparison between study group and control group on the rate of postpartum hemorrhage, blood transfusion, and mean operative time, average hospitalization days after cesarean delivery, expenses was not statistically significant (P > .05). Compared with the control group, other applied supplementary techniques (including uterine tamponade, pelvic arterial embolization, or emergency hysterectomy) for the bleeding from the the placental attachment site is fewer significantly in the study group. No operative accident and hemorrhea-related complication occurred in the 2 groups.Cervical internal os plasty is useful in patients with placenta previa accreta due to its simplicity, utility, and effectivity as well as its capacity for preserving fertility.

Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis of myocardial cells through activation of the JAK2/STAT3 signaling pathway.

Myocardial cell apoptosis mediated by oxidative stress has previously been identified as a key process in ischemic heart disease. Secoisolariciresinol diglucoside (SDG), a polyphenolic plant lignan primarily found in flaxseed, has been demonstrated to effectively protect myocardial cells from apoptosis. In the present study, the role of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was investigated in mediating the protective effect of SDG. Findings of the present study revealed that treatment with H2O2 reduced cell viability and induced apoptosis in H9C2 rat cardiomyocytes. However, SDG was able to reduce the effect of H2O2 in a dose­dependent manner. H2O2 reduced the expression level of phosphorylated STAT3 and inhibited the levels of B­cell lymphoma­extra­large and induced myeloid leukemia cell differentiation protein, which are the STAT3 target genes. Conversely, SDG rescued phosphorylation of STAT3 and increased the levels of STAT3 target genes. Treatment with SDG alone led to a dose­dependent increased phosphorylation of JAK2 and STAT3, without activating Src. Furthermore, the anti­apoptotic effects of SDG were partially abolished by a JAK2/STAT3 inhibitor. In addition, molecular docking revealed that SDG may bind to the protein kinase domain of JAK2, at a binding energy of ­8.258 kcal/mol. Molecular dynamics simulations revealed that JAK2­SDG binding was stable. In conclusion, activation of the JAK2/STAT3 signaling pathway contributed to the anti­apoptotic activity of SDG, which may be a potential JAK2 activator.

Differential gene expression profile of Buyanghuanwu decoction in rats with ventricular remodeling post-myocardial infarction.

OBJECTIVE: To investigate the effect of Buyanghuanwu decoction (BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats. METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD (18 gkg-1d-1) for 90 days. Myocardial collagen was observed by mallory trichrome staining. Capillary density was quantified by using Factor VIII immunohistochemical staining. Differentially expressed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling (DGE) system. Real-time quantitative polymerase chain reaction detecting system (qPCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes. RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2, monocyte chemotactic protein 1, neuropeptide Y, arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment. CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.

Dynamic expression of corticotropin-releasing hormone and urocortin in estrogen induced-cholestasis pregnant rat.

Intrahepatic cholestasis of pregnancy(ICP) is complicated by acute placental-fetal hypoxia. Corticotropin-releasing hormone(CRH) and urocortin(UCN) are vasodilatory regulators of blood flow in the placenta. An ethinylestradiol(EE)-induced cholestasis rat model was reproduced and serum/placental CRH/UCN were detected during 14-21days of gestation(DG). Maternal serum or placental CRH/UCN levels in the control rats were relatively consistent during 14-21DG. Serum CRH was reduced in the EE-treated rats compared with the control rats at 21DG. Regarding serum UCN, we observed a decrease at 17DG as well as an increase at 21DG in the EE-treated rats compared with the controls. Moreover, we observed a noticeable reduction of placental CRH/UCN expression at 17 or 19DG in the EE-treated rats compared with the control rats. The serum bile acids levels exhibited an inverse correlation with placental CRH/UCN expression. EE-induced cholestasis rats might serve as a good model to further investigate the pathological mechanism underlying CRH/UCN dysregulation in ICP.

Aldehyde dehydrogenase-2 protects against myocardial infarction-related cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) has a protective effect on ischemic heart disease. Here, we examined the protective effects of ALDH2 on cardiac fibrosis through modulation of the Wnt/ß-catenin signaling pathway in a rat model of myocardial infarction (MI). METHODS: Wistar rats were divided into the sham (control), MI (model), and ALDH2 activator (Alda-1) groups. After 10 days of treatment, the left ventricular (LV) remodeling parameters of each animal were evaluated by echocardiography. Myocardial fibrosis was evaluated by Masson's trichrome staining and Sirius Red staining. Expression levels of collagen types I and III and α-smooth muscle actin (α-SMA) were examined. Finally, the expression and activity of ALDH2 and the levels of several Wnt-related proteins and genes, such as phosphoglycogen synthase kinase (GSK)-3ß, GSK-3ß, ß-catenin, Wnt-1, WNT1-inducible signaling-pathway protein 1, and tumor necrosis factor (TNF)-α, were also analyzed. RESULTS: After MI, the heart weight/body weight ratio, LV dimension at end diastole, and LV dimension at end systole were decreased, while the LV ejection fraction and LV fractional shortening were increased in the Alda-1 group. Myocardial fibrosis was also reduced in the Alda-1 group, accompanied by decreased expression collagen types I and III and α-SMA. ß-Catenin, phosphorylated GSK-3ß, and Wnt-1 levels were significantly increased in the model group. Interestingly, this alteration was partly reversed by Alda-1 treatment. Immunohistochemical staining showed that numerous WNT1-inducible signaling-pathway protein 1 (WISP-1)- and TNF-α-positive cells were found in the model group. However, few WISP-1- and TNF-α-positive cells were detected in the Alda-1 group. CONCLUSION: The reduction of cardiac fibrosis and the down-regulation of ß-catenin, phosphorylated GSK-3ß, Wnt-1, and WISP-1 may be mediated by increased ALDH2 activity, leading to reduction of MI-related cardiac fibrosis.

Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Meta-Analysis.

Low-dose aspirin (LDA) is thought to prevent preeclampsia in high-risk pregnancy, but it is not universally used out of concern for its efficacy and safety. The authors meta-analyzed 29 randomized controlled trials (RCTs) to evaluate LDA for preventing preeclampsia and its complications. LDA can reduce the incidence of preeclampsia (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.57-0.87), severe preeclampsia (OR, 0.37; 95% CI, 0.23-0.61), preterm birth (OR, 0.81; 95% CI, 0.75-0.88), and intrauterine growth restriction (IUGR) (OR, 0.80; 95% CI, 0.71-0.90). LDA is more effective in reducing incidence of preeclampsia or IUGR if used before 16 gestational weeks than if used later. LDA increases the incidence of placental abruption (OR, 1.35; 95% CI, 1.05-1.73) but not other major complications. The available evidence suggests that LDA is effective in preventing preeclampsia, preterm birth, and IUGR in high-risk pregnancies without posing a major safety risk to mothers or fetuses.

[Placental PHLDA2 gene imprinting in patients with pre-eclampsia].

OBJECTIVE: To observe the imprinting status of maternally expressed gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in placental tissues from patients with pre-eclampsia. METHODS: Samples of placental tissues were collected from women with normal pregnancy (n=21) and pre-eclampsia (n=19). We examined two single nucleotide polymorphism (SNPs) which are prone to variation in PHLDA2: the C/T polymorphism in exon 1 and the G/A polymorphism in exon 2, corresponding to rs13390 (PHLDA2-1) and rs1056819 (PHLDA2-2), respectively. DNA PCR-direct sequencing and cDNA RT-PCR-direct sequencing were applied to detect the special-allelic imprinting status of PHLDA2. RESULTS: No heterozygote was found in placental tissues in relation to C/T polymorphism in PHLDA2 exon 1. Differences in heterozygote in relation to G/A polymorphism in PHLDA2 exon 2 were found between pre-eclampsia (4/19) and normal pregnancy(5/21), but without statistical significance. PHLDA2 cDNA from heterozygotes (PHLDA2-2) were all exclusively monoallelically expressed. CONCLUSION: Similargene polymorphism of PHLDA2 (PHLDA2-1 and PHLDA2-2) in placental tissues was found between pre-eclampsia and normal pregnancies. No loss of imprinting (LOI) of PHLDA2 was found in this study.

Reduced plasma corticotropin-releasing hormone levels during late gestation in patients with intrahepatic cholestasis of pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) may lead to sudden onset of stillbirth, which most likely is related to uteroplacental insufficiency and dysregulation of the fetal blood supply. The relaxing effect of corticotropin-releasing hormone (CRH) on blood vessels was measured to examine the role of CRH in the pathogenesis of ICP. METHODS: Eighty normal pregnant women and 80 ICP patients were divided into four groups of 20 cases, respectively, each based on gestational age from week 34 to 37. Radioimmunoassay was used to measure CRH in plasma samples collected from all of the subjects. RESULTS: Plasma CRH increased markedly from week 34 to 37 in both ICP and healthy patients, but the increase was lower in the ICP group. Plasma CRH was 322 ± 61 pg/ml in mild ICP cases at 37 weeks' compared to 1,066 ± 173 pg/ml in controls (p < 0.05), but only 218 ± 128 pg/ml in severe ICP (p < 0.05). Plasma CRH was significantly lower at all other measured time points in patients with severe ICP. In ICP patients, there was a negative correlation between plasma CRH and total bile acid (TBA). CONCLUSION: A limited increasing CRH level and negative correlation of CRH with TBA were unveiled in ICP patients.