Cerclage placement in twin pregnancies with cervical dilation: a systematic review and meta-analysis

Existing guidelines and studies on the benefits of cerclage in twin pregnancies with a dilated cervix have low reliability and inconsistent conclusions. New randomized control trials and cohort studies focusing on twin pregnancies with cervical insufficiency were published recently. Therefore, this meta-analysis aimed to compare outcomes of cerclage placement and expectant treatment in twin pregnancies with a dilated cervix using recent data. We screened the PubMed, Web of Science, ClinicalTrials.gov, and Cochrane Library databases to identify randomized controlled trials and cohort studies comparing maternal and perinatal outcomes of twin pregnancies with cervical dilation, with and without cerclage placement, published until December 2020. Estimates were pooled using random-effects or fixed-effect models depending on the heterogeneity. Mean difference, 95% confidence interval, and relative risk were used to compare the outcomes. The risk of bias was assessed using the Cochrane Handbook and the Newcastle-Ottawa Scale. The meta-analyses followed the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for systematic reviews of observational studies. Five studies, comprising 275 twin pregnancies, met the inclusion criteria; of those, 167 underwent cerclage and 108 were expectantly managed. Cerclage placement significantly prolonged the interval from the time of diagnosis to delivery and reduced the incidence of preterm delivery, perinatal death, and complications. The fetal outcomes improved significantly in cases managed with cerclage. Therefore, emergent cerclage is a potential option for managing twin pregnancies with cervical dilation of at least 1 cm.</p

Data_Sheet_1_Altered Default Mode Network Is Associated With Cognitive Impairment in CADASIL as Revealed by Multimodal Neuroimaging.PDF

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment, and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important role in cognitive and mental maintenance, have been found in several neurological and mental diseases. However, it remains unclear whether DMN is altered in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Methods: Multimodal imaging methods, including MRI and positron emission tomography (PET), were applied to evaluate the functional, structural, and metabolic characteristics of DMN in 25 patients with CADASIL and 42 healthy controls.Results: Compared with controls, patients with CADASIL had decreased nodal efficiency and degree centrality of the dorsal medial pre-frontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL.Conclusions: Our results suggested that altered network characteristics of DMN might play important roles in cognitive deficits of CADASIL.</p

G-CSF preincubation followed by combination stimulus reduces cell apoptosis analyzed by flow cytometry in HBVECs, but has no significant effect on the mRNA expression of VEGFR-2.

<p>G-CSF (100 nM) was applied 3 h and 12 h before and during combination stimulus. (A) Flow cytometry graphical data for cell apoptosis. (B) Quantitative analysis of cell apoptosis by flow cytometry. (C) VEGFR-2 mRNA expression was analyzed. (D) The relative density of VEGFR-2 mRNA was calculated to that of β-actin. Results were obtained from three independently repeated experiments. **p<0.01 vs. control. ## p<0.01 for Com + G-CSF vs. Com. Com: combination stimulus.</p

G-CSF pretreatment affects the expression of cycle proteins in HBVECs following combination stimulus.

<p>Cells were incubated with G-CSF (100 nM) for 12 h and thereafter exposed to combination stimulus together with G-CSF (100 nM). The protein expression of hCdc14A (A), cyclinB (C), cyclinD (E), cyclinE (G) and p53 (I) was analyzed. The relative density of hCdc14A (B), cyclinB (D), cyclinD (F), cyclinE (H) and p53 (J) was calculated to that of β-actin. The results showed that G-CSF treatment enhanced the expression of hCdc14A, cyclinB and cyclinE, and reduced p53 level, compared to combination stimulus alone. Results were obtained from three independently repeated experiments. *p<0.05 vs. control. #p<0.05 for Com + G-CSF vs. Com. Com: combination stimulus.</p

Alterations in cell ultrastructure examined by TEM during the addition of G-CSF (100 nM) to HBVECs for 12 h before and throughout the combination stimulus.

<p>(A) The intact cell ultrastructure under normal condition. (B) Combination stimulus led to organelles loss and apoptotic body formation. (C) G-CSF remarkablely ameliorated these injured changes, such as the significant decrease in apoptotic bodies. (D) Quantitative assay of apoptotic bodies. Twenty-five randomly-chosen fields were observed in each sample. Three independently repeated experiments were conducted. *<i>p</i><0.05 vs. control. #<i>p</i><0.05 for Com + G-CSF vs. Com. Com: combination stimulus. Original magnification: 90,000×.</p

Protective functions of G-CSF in combination stimulus depends on activity of MAPK and Akt signaling cascades.

<p>The addition of ERK1/2 or Akt inhibitors (30 nM PD98059, 20 μM LY294002) 30 min before combination stimulus almost completely abrogated the protective functions of G-CSF (100 nM) following combination stimulus by decreasing cell viability (A) and increasing caspase-3 activity (B). However, the administration of JNK or p38 inhibitors (30 nM SP600125, 30 nM SB203580) produced the opposite effects (A, B). Three independently repeated experiments were conducted. *p<0.05 and **p<0.01 vs. combination stimulus. #p<0.05 and ##p<0.01 for combination stimulus + G-CSF + inhibitors vs. combination stimulus + G-CSF.</p

Combination stimulus and combination with G-CSF treatment affect the phosphorylation levels of MAPK and Akt signaling cascades in HBVECs.

<p>(A) ELISA showed that continuous combination stimulus up-regulated p-JNK and p-p38 expression whereas down-regulated p-ERK1/2 and p-Akt expression. (B) Immunofluorescence experiments indicated that G-CSF (100 nM) pretreatment for 12 h before and during combination stimulus increased p-ERK1/2 and p-Akt expression at 2 h and 4 h of combination stimulus, respectively, while inhibited p-p38 and p-JNK expression at the same time points. HBVECs were stained for p-Akt and p-JNK in red, p-ERK1/2 and p-p38 in green, and nuclei with DAPI in blue. (C) Quantitative analysis about fluorescence intensity of phosphorylated proteins by immunofluorescence experiments and three randomly-chosen fields were detected. Results were obtained from three independently repeated experiments. *p<0.05 and **<i>p</i><0.01 vs. control. #<i>p</i><0.05 and ##<i>p</i><0.01 vs. Com. Com: combination stimulus.</p

G-CSF pretreatment reduces combination stimulus-induced calcium ion levels measured by fluorescent probe Fluo-3/AM. G-CSF (100 nM) was added to the medium 12 h before and subsequent exposure to combination stimulus.

<p>(A) Combination stimulus induced high fluorescence intensity relative to the normal condition or G-CSF alone. Importantly, G-CSF pretreatment greatly reversed these changes. (B) Quantitative analysis about fluorescence intensity. Three independently repeated experiments were conducted. **p<0.01 vs. normal control. #p<0.05 for Com + G-CSF vs. Com. Com: combination stimulus.</p

G-CSF facilitates cell cycle progression under combination stimulus in HBVECs.

<p>(A-C) Flow cytometry graphical data for cell cycle. (D) Quantitative assay of cell cycle indicated that G-CSF (100 nM) pretreatment largely enhanced the combination stimulus-induced decreases in cell proportion in S and G2/M phases. Three independently repeated experiments were conducted. *p<0.05 for combination stimulus vs. control. #p<0.05 for combination stimulus + G-CSF vs. combination stimulus alone.</p

G-CSF pretreatment leads to the formation of depolymerized skeleton structure in HBVECs after combination stimulus by immunofluorescence analysis.

<p>(A) The clear filamentary structure in normal cells. (B) The fibrous fracture after combination stimulus. (C) The depolymerized skeleton structure after G-CSF (100 nM) exposure following combination stimulus. Cells were stained for F-actin in red and nuclei with DAPI in blue. (D) Quantitative assay of depolymerized F-actin. One-hundred randomly-chosen cells were observed in each sample and three independently repeated experiments were conducted. ##p<0.01 for Com + G-CSF vs. Com alone. Com: combination stimulus.</p