The optimal dosage of aspirin for preventing preeclampsia in high-risk pregnant women: A network meta-analysis of 23 randomized controlled trials.

This study aimed to assess the effectiveness and optimal dosage of aspirin in preventing preeclampsia in high-risk pregnant women. Traditional and network meta-analyses were conducted on data from 23 randomized controlled trials involving 10 547 pregnant women. The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect observed at a dosage of 80-100 mg/day (OR = 0.51, 95%CI [0.36, 0.72]). No significant differences were found in the occurrence of postpartum hemorrhage (OR = 1.03, 95%CI [0.79, 1.33]), small for gestational age (OR = 0.83, 95%CI [0.50, 1.35]), placental abruption (OR = 0.96, 95%CI [0.53, 1.73]), and intrauterine growth restriction (OR = 0.63, 95%CI [0.45, 1.86]) between women taking aspirin and those taking placebos. Different doses of aspirin showed a reduction in preeclampsia incidence, but there was no significant difference in efficacy between the dosage groups. Side effects did not significantly differ between placebo and different aspirin dosage groups. SUCRA analysis suggested that 80-100 mg/day may be the optimal dosage, prioritizing both effectiveness and minimizing side effects. Sensitivity analysis confirmed the robustness of the findings. However, improvements are needed in addressing issues like loss to follow-up, reporting bias, and publication bias. In conclusion, a dosage of 80-100 mg/day is recommended for preventing preeclampsia in high-risk pregnant women, although individual circumstances should be considered for optimizing the balance between effectiveness and safety.

Clinical value of mean platelet volume in predicting and diagnosing pre-eclampsia: a systematic review and meta-analysis.

Background: Pre-eclampsia (PE) is a severe pregnancy complication. Thrombocytopenia and platelet dysfunction are common hematology disorders in PE. Previous studies considered mean platelet volume (MPV), a functional marker of platelets, as a potentially useful predictor for the diagnosis of PE. Methods: PubMed, China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Embase, Wanfang, VIP, and Cochrane Library databases were searched to gather diagnostic trials evaluating the diagnosis of PE using MPV, from their inception to 13 March 2023. We also searched Google Scholar and Baidu. Results: A total of 22 studies from 20 articles were found. The pooled diagnostic accuracy of the MPV for PE recognition was as follows: sensitivity (SEN) 0.676 [95% confidence interval (CI) (0.658-0.694)], specificity (SPE) 0.710 [95% CI (0.703-0.717)], and diagnostic odds ratio (DOR) 7.012 [95% CI (4.226-11.636)], and the SROC-AUC and Q* indices were 0.7889 and 0.7262, respectively. The pooled SEN, SPE, and DOR of the diagnostic accuracy of MPV for PE before 16 weeks of gestation were 0.707 [95% CI (0.670-0.743)], 0.639 [95% CI (0.611-0.667)], and 4.026 [95% CI (2.727-5.943)], and the SROC-AUC and Q* indices were 0.7278 and 0.6753, respectively. For the interval of truncation values between 9 and 10 fl, the SROC-AUC and Q* indices for MPV were 0.8856 and 0.8162, respectively. Conclusions: Available evidence suggests that MPV has a moderate predictive and diagnostic value for PE, particularly in diagnosing after 20 weeks of gestation. The diagnostic accuracy is higher when the MPV cut-off falls between 9 and 10 fl. The sensitivity of MPV alone in diagnosing PE is not high, and the combination of other markers for predictive diagnosis may better differentiate PE. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425154, identifier: CRD42023425154.

Diagnostic value of platelet to lymphocyte ratio in preeclampsia: a systematic review and meta-analysis.

BACKGROUND: Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge. Although several clinical studies suggested that PLR is able to diagnose PE, there has been no systematic evaluation of the diagnostic utility. OBJECTIVES: To examine the diagnostic accuracy and potential applicability of PLR in the detection of PE. STUDY DESIGN: Seven databases were searched using a combination of PLR and PE terms, and all potentially pertinent studies were systematically searched up to March 2023. All potentially relevant studies both prospective and retrospective were reviewed. To assess the diagnostic value of PLR for PE, pooled sensitivity (Sen), specificity (Spe), diagnostic odds ratio (DOR) and area under the summary receiver operating characteristic curve (SROC-AUC) were calculated. RESULTS: Thirteen studies were enrolled in the meta-analysis. In the second and third trimesters, the PLR suggested a diagnostic value for PE with a pooled Sen of 54.7% [95% confidence interval (CI) (51.7, 57.6)], Spe of 77.8% [95% CI (75.5, 80.0)], + LR of 2.457 [95% CI (1.897, 3.182)], -LR of 0.584 [95% CI (0.491, 0.695)], DOR of 4.434 [95% CI (3.071, 6.402)], the SROC-AUC of 0.7296 and the standard error (SE) of 0.0370. CONCLUSION: For the diagnosis of PE, PLR has a limited sensitivity but an acceptable specificity, and showed moderate accuracy. Further using complete blood count (CBC) indicators such as PLR alone or in combination to diagnose and predict PE could reduce healthcare costs and improve maternal and child prognosis.

[Extracellular Signal-regulated Kinase 1/2 Signaling Regulates Cell Invasion:a Review].

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Calcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium. METHOD: Eight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0-1.49 g), and the low-dose group (<1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia. RESULTS AND DISCUSSION: A total of 48 studies were incorporated into the final analyses. All doses of calcium supplementation reduced the incidence of gestational hypertension in the low-risk population (low dose - three studies; medium dose- 11 studies; high dose- 28 studies), whereas the medium-dose (three studies) reduced the incidence of gestational hypertension in high-risk groups. Moreover, a medium dose of calcium supplementation had the maximum effect in reducing gestational hypertension in low-risk and high-risk populations. The medium (three studies) and high doses (13 studies) of calcium supplementation reduced the incidence of pre-eclampsia in the low-risk groups. However, a medium-dose calcium supplementation maximally prevented pre-eclampsia in the low-risk population. The authenticity and reliability of the results were reduced due to the limitations of contemporary studies in terms of experimental design, result measurement, statistics, and evidence quality. Therefore, high-quality studies with larger sample size are required to evaluate further the effect of calcium supplementation in preventing gestational hypertension and pre-eclampsia.

The Potential Role of Serum Exosomes in Preeclampsia.

Preeclampsia is a serious pregnancy-specific disease that affects about 5%-8% of pregnant women and is the main reason for the increase in maternal and perinatal mortality. Due to unknown etiology, preeclampsia is still the main cause of increased mortality in maternal and perinatal infants, which is mainly manifested by new hypertension after 20 weeks of pregnancy. As the pathogenesis has not been fully elucidated, early diagnosis and full treatment are lacking. Exosomes secreted from the placenta to the peripheral circulation may be involved in the pathogenesis of preeclampsia and can be detected from the plasma of pregnant women after 6 weeks of pregnancy. Related studies have shown that the levels of exosomes in preeclampsia have changed, and the protein and miRNA expression profiles are also different. Therefore, monitoring changes in plasma exosomes and expression profiles may provide new ideas and new perspectives for the prediction, diagnosis and treatment of preeclampsia.

Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis.

PURPOSE: The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms. METHODS: Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax). RESULTS: Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury. CONCLUSION: Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.

Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells through induction of apoptosis and G2/M cell cycle arrest.

BACKGROUND: The plant Euphorbia helioscopia L. has been used in traditional Chinese medicine for treating various disorders such as tuberculosis and edema. The aim of this study was to investigate the effect of euphornin, a bioactive compound isolated from E. helioscopia, on proliferation of human cervical adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and cell cycle progression. MATERIALS AND METHODS: The sulforhodamine B assay was used to study the effect of euphornin on the proliferation of HeLa cells. Morphological changes to cell nuclei were identified after Hoechst 33342 staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting was applied to investigate the influence of euphornin on cell cycle progression. Proteins were obtained from HeLa cells and analyzed by Western blots. RESULTS: A cell viability assay showed that euphornin inhibited proliferation of HeLa cells in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis in a concentration-dependent manner, with the rates of apoptosis ranging from 25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also markedly increased by euphornin treatment. Analysis of cell cycles indicated that euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein. The various assays demonstrated that euphornin treatment resulted in a significant suppression of cell growth accompanied by G2/M cell cycle arrest and increased rate of apoptosis via mitochondrial and caspase pathways. CONCLUSION: Our findings suggest that euphornin has the potential to be used as a cancer therapeutic agent against human cervical adenocarcinoma.