Anti-hypertensive therapy for preeclampsia: a network meta-analysis and systematic review.

BACKGROUND: Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. METHODS: This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31st of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software. RESULTS: We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study. CONCLUSION: According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.

Preeclampsia in pregnant women with polycystic ovary syndrome: risk factor analysis based on a retrospective cohort study.

OBJECTIVES: To compare the clinical characteristics of pregnant women with polycystic ovary syndrome (PCOS) and perinatal outcomes with or without preeclampsia (PE) and to factors that are potentially associated with the onset of PE. MATERIAL AND METHODS: This was a retrospective study of pregnant women diagnosed with PCOS from January 2017 to December 2021. Eligible patients were divided into two groups based on the presence or absence of preeclampsia: a PE group and a non-PE group. Demographics, clinical characteristics, maternal and perinatal outcomes, and potential factors linked to disease recurrence were analyzed. RESULTS: In total, 616 patients were enrolled and respectively classified into the PE group (n = 51) and the non-PE group (n = 565). The incidence of PE in pregnant women with PCOS was 8.28%; this was significantly higher than that in non-PCOS pregnant women (3.22%, p < 0.001). Logistic regression analysis of the predictive factors for PE in women with PCOS revealed that the combination of maternal hyperandrogenism, a pre-pregnancy BMI ≥ 24 kg/m², and a family history of cardiovascular disease (CVD) and assisted reproductive techniques (ART) exhibited the steepest receiver-operating characteristic (ROC) curve value at 0.797 [95% confidence interval (CI): 0.733-0.862]. CONCLUSIONS: Patients with PCOS have a higher incidence of PE. We identified a series of significant and independent factors associated with PE in PCOS: maternal hyperandrogenism, a pre-pregnancy BMI ≥ 24 kg/m², and a family history of CVD and ART.

Application of low molecular weight heparins in umbilical artery thrombosis: A case series and review of the literature.

RATIONALE: Low molecular weight heparins are widely used in various thrombotic diseases and exert a preventive effect on thrombosis in high-risk patients. Umbilical artery thrombosis (UAT) is a rare occurrence that is difficult to detect during routine prenatal visits but can lead to adverse perinatal outcomes. PATIENT CONCERNS: The aim of this study was to elucidate the therapeutic effect of low molecular weight heparins on UAT and to provide a new treatment option for the timing of delivery timing. DIAGNOSES AND INTERVENTIONS: A retrospective study was conducted on cases involving thrombosis of the umbilical cord enrolled from July 2017 to July 2022. Data were acquired and analyzed from medical records and the final diagnosis was confirmed by histopathology. All included patients received LWMHs therapy after initial diagnosis of UAT. OUTCOMES: The mean age of the 10 pregnant women recruited into this study was 27.9 ± 4.0 year-of-age; 1 (10%) was elderly. The gestational age at diagnosis was 29.9 ± 3.7 weeks, the gestational age at termination was 36.3 ± 2.5 weeks and the mean gestational age of extension was 6.4 ± 4.2 weeks. Low molecular weight heparin sodium was administered after umbilical artery embolism was detected on ultrasound. The LWMHs treatment received by the included patients in this study was subcutaneous injection. The specific usage varies due to the types of LWMHs. Of the 10 cases, 5 (50%) had fetal distress but all fetuses were born alive without neonatal asphyxia. With regards to delivery mode, 9 pregnancies were terminated by cesarean section. LESSON: Early anticoagulant treatment with LWMHs may improve pregnancy outcomes. The timing and mode of termination of pregnancy should be determined according to the condition of the mother and the fetus along with the gestational age.

Endometrial Cytology in Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Because the incidence of endometrial cancer has been increasing every year, it is important to identify an effective screening method for it. The endometrial cytology test (ECT) is considered to be the more acceptable technique compared to invasive endometrial sampling. METHODS: The study followed the Priority Reporting Project for Systematic Evaluation and Meta-Analysis (PRISMA-DTA) protocol. This systematic rating searched EMBASE and Web of Science databases for studies on ECT for endometrial cancer from the databases' dates of inception to 30 September 2022. All literature screening and data extraction were performed by two researchers, while the methodological quality of the included studies was assessed against defined inclusion criteria. And a third researcher resolves the disagreements. RESULTS: Twenty-six studies were eventually included in this final analysis. Meta-analysis results showed that the diagnostic accuracy characteristics of ECT for endometrial cancer were as follows: combined sensitivity = 0.84 [95% confidence interval (CI) (0.83-0.86)], combined specificity = 0.98 [95% CI (0.98-0.98)], combined positive likelihood ratio = 34.65 [95% CI (20.90-57.45)], combined negative likelihood ratio = 0.21 [95% CI (0.15-0.30)], and area under the summary receiver operating characteristic curve = 0.9673. CONCLUSIONS: ECT had the ability to detect endometrial cancer with strong specificity, although some studies have demonstrated significant differences in sensitivity.

The role of ferritin and iron dextran in exacerbating preeclampsia in an L-NAME-treated rat model.

Background: Preeclampsia (PE) occurs in the second half of pregnancy and contributes to maternal and perinatal morbidity and mortality. Ferritin plays a key role in pregnancy, but the underlying mechanisms of its involvement in PE remain elusive. This study aimed to investigate the effects of ferritin concentrations and ferroptosis levels on PE rats at different stages of pregnancy. Methods: A PE rat model was established by administering nitro-L-arginine methyl ester (L-NAME; 60 mg/kg/day, orally) between the 13th and 19th days of pregnancy. Iron dextran (ID) was used to induce ferroptosis, whereas deferoxamine (DFO) was used to prevent ferroptosis. Pathological changes in the placenta and vascular system were observed by hematoxylin and eosin (H&E) staining. Oxidative stress levels, blood pressure, and urine protein levels were assessed. Inflammatory cytokines and cellular ferritin (FER)-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to assess apoptosis- and ferroptosis-related proteins. Results: The data showed that L-NAME elevated blood pressure and urine protein levels in pregnant rats, while treatment with DFO-late and ID-early reduced them. Placental and vascular damage were ameliorated, and the levels of nitric oxide (NO), nitric oxide synthase (NOS), and superoxide dismutase (SOD) were increased. In contrast, the generation of reactive oxygen species (ROS), malonaldehyde (MDA), inflammatory factors, and FER-related proteins were suppressed, accompanied by reduced apoptosis- and increased ferroptosis-related proteins in the DFO-late group. Conclusions: Our results suggested that decreased ferritin levels in early pregnancy or elevated ferritin levels in late pregnancy in an L-NAME-treated rat model accelerated ferroptosis and exacerbated PE symptoms.

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.

Predictive factors associated with disease recurrence in patients with severe intrahepatic cholestasis of pregnancy: a retrospective study of 118 cases.

PURPOSE: To compare the clinical characteristics of pregnant women and perinatal outcomes with or without recurrent severe intrahepatic cholestasis of pregnancy (sICP), and identify possible factors associated with disease recurrence. METHODS: A retrospective study of 164,603 deliveries was performed to identify pregnant women diagnosed with sICP in the previous pregnancy from January 2012 to December 2020. Eligible patients were divided into two subgroups according to the status of disease recurrence in the second pregnancy: recurrent severe ICP (r-sICP) and non-recurrent severe ICP (nr-sICP). Demographics, clinical characteristics, maternal and perinatal outcomes, and potential factors linked to disease recurrence were analyzed. RESULTS: Totally 118 patients were enrolled and respectively classified into the r-sICP group (n = 63) and the nr-sICP group (n = 55). The proportion of hepatitis B virus (HBV) infection (HBsAg+, HBeAg+, HBcAb+) and early-onset ICP (<28 weeks) in the r-sICP group in the previous pregnancy were higher than those in the nr-sICP group. In the second delivery, neonatal outcomes in the r-sICP group were worse than those in the nr-sICP group. Logistic regression analysis of predictive factors for disease recurrence in the second delivery revealed that the combination of HBV infection and early-onset ICP in the previous delivery had the steepest receiver-operating characteristic (ROC) curve value 0.720 (95%CI: 0.629-0.812). CONCLUSION: Patients with sICP displayed a higher recurrence rate in the second pregnancy. Being <28 weeks at the time of ICP diagnosis and having HBV infection in the previous delivery appear to be independent predictive factors for disease recurrence of sICP.

Identification of endometriosis-associated genes and pathways based on bioinformatic analysis.

ABSTRACT: Endometriosis is associated with dysmenorrhea, chronic pelvic pain, and infertility. The specific mechanism of endometriosis remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of endometriosis.The gene expression profiles of GSE25628, GSE5108, and GSE7305 were downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using GEO2R. The database for annotation, visualization, and integrated discovery (DAVID) was utilized to analyze the functional enrichment, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using search tool for the retrieval of interacting genes and cytoscape.A total of 119 common differentially expressed genes were extracted, consisting of 51 downregulated genes and 68 upregulated genes. The enriched functions and pathways of the DEGs and hub genes include DNA strand separation, cellular proliferation, degradation of the extracellular matrix, encoding of smooth muscle myosin as a major contractile protein, exiting the proliferative cycle and entering quiescence, growth regulation, and implication in a wide variety of biological processes.A bioinformatics approach combined with cell experiments in this study revealed that identifying DEGs and hub genes leads to better understanding of the molecular mechanisms underlying the progression of endometriosis, and efficient biomarkers underlying this pathway need to be further investigated.

Can prophylactic transvaginal cervical cerclage improve pregnancy outcome in patients receiving cervical conization? A meta-analysis.

OBJECTIVES: Cervical conization could increase the risk of cervical insufficiency. This study systematically evaluated the value of prophylactic transvaginal cervical cerclage following cervical conization with regards to pregnancy outcome. MATERIAL AND METHODS: We performed a systematic review of the literature, using Web of Science, and Embase, the published time ranged from the date that database established to December 2019. Pregnant patients, who had a previous history of cervical conization for CIN or early cervical cancer, were enrolled. Two researchers searched these databases and estimated the included studies' quality independently, depending on the same criteria. RESULTS: Our meta-analysis is incorporate 3560 cases eventually. Meta-analysis showed that when compared to the no-cerclage group, the risk ratio (RR) of preterm birth in the prophylactic transvaginal cervical cerclage group was 1.85 [95% confidence interval (CI): 1.22-2.80; p = 0.004]; the RR of premature rupture of membranes was 1.5 (95% CI: 1.17-1.93; p = 0.001). CONCLUSIONS: The rates of preterm birth were significantly higher in women following cervical conization with transvaginal cerclage than those without cerclage.

Bioinformatics-based identification of miRNA-, lncRNA-, and mRNA-associated ceRNA networks and potential biomarkers for preeclampsia.

This study aimed to identify significantly altered long non-coding RNAs (lncRNAs), microRNAs (miRNAs), mRNAs, pathways in preeclampsia (PE), and to investigate their targeted relationships and biological functions.GSE96985 from Gene Expression Omnibus database was extracted, involving 3 PE and 4 normal tissues. After the differential expression analysis of miRNAs, lncRNAs, and mRNAs using the limma package, protein-protein interaction (PPI) network and module analyses were performed for differentially expressed mRNAs (dif-mRNAs). Combined with the miRanda and miRWalk tools, a regulatory relationship between dif-miRNAs and dif-mRNAs/lncRNAs (dif-mRNAs/dif-lncRNAs) was predicted. Finally, mRNA-miRNA-lncRNA regulatory network construction was performed using Cytoscape software.A total of 511 dif-mRNAs were screened in PE. The top 5 nodes in the PPI networks included up-regulated complement component 3 (C3), C-X-C motif chemokine ligand 8 (CXCL8), and fibronectin 1 (FN1). Three significant network modules were identified for dif-mRNAs. C3 and CXCL8 were identified in module A, and FN1 was identified in module C. A disintegrin and metalloproteinase with thrombospondin motifs 6 (ADAMTS6) was down-regulated by the miR-210-3p. Therefore, lnc-CTD-2383M3.1 functions as a competing endogenous RNA in ADAMTS6 expression regulation by competitively binding to miR-210-3p during the regulation process of PE.C3, CXCL8, FN1, and ADAMTS6 might be involved in the development of PE. The lnc-CTD-2383M3.1-miR-210-3p-ADAMTS6 axis might be a potential regulatory mechanism in PE.

Hepatitis B infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Viral hepatitis type B is caused by hepatitis B virus (HBV) infection. Several studies have linked HBV infection to a higher risk of developing intrahepatic cholestasis of pregnancy (ICP), although some give contradictory results. To investigate the association and estimated risk of ICP in patients with HBV infection, we conducted this meta-analysis to summarize all available evidence. METHODS: This study consists of 2 meta-analyses. A literature search was performed using MEDLINE and EMBASE from inception to July 2019. The first study included studies that reported associations between HBV infection and the risk of ICP. The second analysis included studies comparing the risk of HBV infection in ICP patients with those without ICP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effect, inverse variance method. RESULTS: Four studies were included in both analyses. The OR of ICP in HBV-infected pregnant women compared with non-HBV pregnant women was 1.68 (95% CI 1.43-1.97; I = 0%). The OR of HBV infection among ICP patients compared with non-ICP patients was 1.70 (95% CI 1.44-2.01; I = 0%). CONCLUSIONS: Our meta-analysis demonstrates not only a higher risk of ICP among HBV-infected pregnant women but also an increased risk of HBV infection among ICP patients. These findings suggest that HBV is a high-risk factor for ICP and screening for hepatitis B in women with ICP symptoms may be beneficial.

Clinical characteristics and pregnancy outcomes of atypical hemolysis, elevated liver enzymes, and low platelets syndrome: A case series.

RATIONALE: Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a serious and rare disease, which is secondary to preeclampsia in most cases. Hypertension is usually considered as a premonitory symptom of HELLP syndrome. In some patients with HELLP syndrome; however, they develop hypertension very late, even after liver enzymes are elevated or platelet count is decreased. This condition is known as atypical HELLP syndrome. PATIENT CONCERNS: We screened and identified 4 cases of atypical HELLP syndrome in our hospital database from January 2007 to December 2018. All patients had a history of nonspecific symptoms for a few days before hospital admission, such as dizziness, nausea, and vomiting. They developed hypertension after abnormalities were noted in liver enzymes and platelet count. DIAGNOSES: They were diagnosed with atypical HELLP syndrome. INTERVENTIONS: These patients received same treatments as those with HELLP syndrome. Two patients took oral antihypertensive treatment to normalize the blood pressure. OUTCOMES: In our patients, both mothers and neonates had favorable outcomes. In follow-ups, they reported no incidences of high blood pressure after recovery from atypical HELLP syndrome. LESSONS: These cases provided additional clinical evidences of atypical HELLP syndrome. The incidence of atypical HELLP syndrome is extremely low. Hypertension is not essential for the diagnosis of HELLP syndrome, and can even appear after the onset of laboratory abnormalities. Advanced age, multiple pregnancies, hepatitis B virus infection, and obesity may be potential risk factors for atypical HELLP syndrome. Blood pressure should be monitored closely after delivery.

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.

Efficacy of robotic radical hysterectomy for cervical cancer compared with that of open and laparoscopic surgery: A separate meta-analysis of high-quality studies.

BACKGROUND: To perform a meta-analysis of high-quality studies comparing robotic radical hysterectomy (RRH) vs laparoscopic radical hysterectomy (LRH), and open radical hysterectomy (ORH) for the treatment of cervical cancer. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed to identify studies that compared RRH with LRH or ORH. The selection of high-quality, nonrandomized comparative studies was based on a validated tool (methodologic index for nonrandomized studies) since no randomized controlled trials have been published. Outcomes of interest included conversion rate, operation time, intraoperative estimated blood loss (EBL), length of hospital stay (LOS), morbidity, mortality, number of retrieved lymph nodes (RLNs), and long-term oncologic outcomes. RESULTS: Twelve studies assessing RRH vs LRH or ORH were included for this meta-analysis. In comparison with LRH, there was no difference in operation time, EBL, conversion rate, intraoperative or postoperative complications, LOS, and tumor recurrence (P > .05). Compared with ORH, patients underwent RRH had less EBL (weighted mean difference [WMD] = -322.59 mL; 95% confidence interval [CI]: -502.75 to -142.43, P < .01), a lower transfusion rate (odds ratio [OR] = 0.14, 95% CI: 0.06-0.34, P < .01), and shorter LOS (WMD = -2.71 days; 95% CI: -3.74 to -1.68, P < .01). There was no significant difference between RRH and LRH with respect to the operation time, intraoperative or postoperative complications, RLN, and tumor recurrence (P > .05). CONCLUSION: Our results indicate that RRH is safe and effective compared to its laparoscopic and open counterpart and provides favorable outcomes in postoperative recovery.

Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice.

Monoammonium glycyrrhizinate (MAG) was the aglycone of glycyrrhizin derived from licorice. In this study, the anti-inflammatory effects of MAG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with MAG prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio, in total leukocyte number and neutrophil percent in the BALF, and in myeloperoxidase (MPO) activity of lung in dose-dependent manners. At the same time, pretreatment with MAG also significantly improved the super oxide dismutase (SOD) activity and induced the malondialdehyde (MDA) content in the bronchoalveolar lavage fluid (BALF). Importantly, pretreatment with MAG prevented an increase in cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) activity of lung in a dose-dependent manner. In addition, it can up-regulate the interleukin-10 (IL-10) level and down-regulate the tumor neurosis factor-α (TNF-α) level in the lung tissue of ALI mice. These results showed that anti-inflammatory effects of MAG against the LPS-induced ALI may be due to its ability of primary inhibition of cAMP-PDE activity, oxidative stress and its regulation of cytokine effects. Thus the results support that use of MAG is beneficial in the treatment of ALI and ARDS.

[Protective effect against monoammonium glycyrrhizinate on lipopolysaccharide-induced acute lung injury in mice].

The aim of this study is to investigate the effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide (LPS) -induced acute lung injury (ALI) and its anti-inflammatory mechanism in mice. All male ICR mice were randomly divided into six groups: LPS group; control group; MAG 3, 10, and 30 mg x kg(-1) groups; and dexamethasone (DXM) 5 mg x kg(-1) group. Lung dry weight and wet weight percentage and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and lung tissues was detected by cell count and morphological analysis. The levels of TNF-alpha and IL-10 in lung were detected by ELISA. MPO activity was determined followed the specification. MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice. These results suggested that the protective effect of MAG in mice on LPS induced ALI was associated with the regulation of TNF-alpha/IL-10 balance, and MAG maybe a potentially treatment for ALI/ARDS.