Background: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. Methods: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium. Results: We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. Conclusions: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

Objective: Cesarean section (CS) is one of the most frequently performed major surgical interventions. Local anesthetic techniques, a universal component of perioperative multimodal analgesia, are reportedly effective in reducing pain scores and opioid requirements. However, the optimal local anesthetic technique for postoperative CS pain remains unclear. Methods: Six databases were searched, and a Bayesian network meta-analysis was performed. The outcomes included cumulative morphine consumption and pain scores at four time points, time to first analgesic request, postoperative nausea and vomiting, pruritus, and sedation. Results: Sixty-eight studies with 5039 pregnant women were included. Six local anesthetic techniques were involved, including transversus abdominis plane block (TAPB), ilioinguinal and iliohypogastric nerve block, quadratus lumborum blocks, transversalis fascia plane block, erector spinae block, and wound infiltration. Compared to inactive controls, TAPB reduced cumulative morphine consumption at 6, 12, 24, and 48 h, pain scores at 6, 12, and 24 h (with the exception of 24 h at rest), the risk of postoperative nausea and vomiting, and sedation. Compared with inactive controls, ilioinguinal and iliohypogastric nerve block reduced cumulative morphine consumption at 6 and 24 h and pain scores at 6, 12, and 24 h during movement. Compared with inactive controls, quadratus lumborum blocks reduced cumulative morphine consumption at 24 and 48 h and pain scores at 6 and 12 h and lengthened the time to first analgesic request. Compared with inactive controls, wound infiltration reduced cumulative morphine consumption at 12 and 24 h, pain scores at 12 and 24 h during movement, and risk of sedation. Compared with inactive controls, erector spinae block reduced pain scores at 6 and 12 h. Transversalis fascia plane block was found to have similar outcomes to inactive controls. Conclusion: TAPB is the most comprehensive local anesthetic technique for postoperative CS analgesia in the absence of intrathecal morphine.

Background: Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease in children. The incidence of cardiomyopathy induced by DMD increases with age. Left ventricular ejection fraction usually fails to reflect the subclinical left ventricular dysfunction. Several studies have assessed this dysfunction using myocardial strain measured by speckle-tracking echocardiography (STE). However, the results were inconsistent and incomplete. Methods: Several databases were searched from their inception to February 5, 2020. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for myocardial strain between DMD and healthy controls and a meta-analysis was conducted. Trial sequential analysis estimated whether the resulting evidence was sufficient. Results: Eight studies with a total of 269 DMD children and 299 healthy participants were included. STE revealed that global longitudinal strain (GLS), global circumferential strain, average longitudinal strain (measured by two-dimensional STE at the apical four-chamber view), and average circumferential strain (measured by two-dimensional STE at the papillary muscle short-axis level) decreased (WMD = 4.17, 95% CI: 3.03–5.32; WMD = 3.98, 95% CI: 0.29–7.68; WMD = 4.18, 95% CI: 2.75–5.62; and WMD = 4.90, 95% CI: 2.38–7.43, respectively; all P < 0.05) compared with the controls and global radial strain was unchanged in the DMD group (WMD = − 4.33, 95% CI: − 9.53–0.87, P = 0.103). Trial sequential analysis indicated that available GLS samples were sufficient and confirmed that adequate evidence was accumulated. The credibility of other myocardial strains was questioned due to insufficiently involved studies. Conclusion: GLS can be useful for early detection of left ventricle myocardial dysfunction in children with DMD.

Background: Patients usually suffer acute pain after cardiac surgery. Numerous regional anesthetic techniques have been used for those patients under general anesthesia. The most effective regional anesthetic technique was still unclear.Methods: Five databases were searched, including PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library. The efficiency outcomes were pain scores, cumulative morphine consumption, and the need for rescue analgesia in this Bayesian analysis. Postoperative nausea, vomiting and pruritus were safety outcomes. Functional outcomes included the time to tracheal extubation, ICU stay, hospital stay, and mortality.Results: This meta-analysis included 65 randomized controlled trials involving 5,013 patients. Eight regional anesthetic techniques were involved, including thoracic epidural analgesia (TEA), erector spinae plane block, and transversus thoracic muscle plane block. Compared to controls (who have not received regional anesthetic techniques), TEA reduced the pain scores at 6, 12, 24 and 48 h both at rest and cough, decreased the rate of need for rescue analgesia (OR = 0.10, 95% CI: 0.016–0.55), shortened the time to tracheal extubation (MD = −181.55, 95% CI: −243.05 to −121.33) and the duration of hospital stay (MD = −0.73, 95% CI: −1.22 to −0.24). Erector spinae plane block reduced the pain score 6 h at rest and the risk of pruritus, shortened the duration of ICU stay compared to controls. Transversus thoracic muscle plane block reduced the pain scores 6 and 12 h at rest compared to controls. The cumulative morphine consumption of each technique was similar at 24, 48 h. Other outcomes were also similar among these regional anesthetic techniques.Conclusions: TEA seems the most effective regional postoperative anesthesia for patients after cardiac surgery by reducing the pain scores and decreasing the rate of need for rescue analgesia.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, ID: CRD42021276645

Left ventricular diastolic function is impaired during pregnancy. However, changes in left atrial (LA) function remain unclear. We aimed to evaluate changes in LA function during pregnancy using two-dimensional speckle tracking echocardiography (2DSTE). 50 pregnant and 50 healthy nulliparous (control group) women were enrolled in this study. All pregnant women were followed up postpartum in sixth-month. The LA maximum volume, LA minimal volume and LA preatrial contraction volume were obtained using biplane modified Simpson’s method. LA filling volume, LA expansion index, LA ejection fraction, passive volume, passive emptying index, active volume, and active emptying index were calculated. LA longitudinal systolic strain (SS), systolic strain rate (s-SR), early diastolic strain rate (e-SR), and late diastolic strain rate (a-SR) were obtained by 2DSTE. Compared to the control group, the reservoir function was increased in pregnant patients (P<0.05); conduit function was decreased in pregnant patients (P<0.05); booster pump function was increased in pregnant patients (P<0.05). There was no statistically significant difference between the control group and postpartum group. LA reservoir and booster pump function were increased, while conduit function was decreased during pregnancy using 2DSTE. The changes were reversible. 2DSTE can easily assess LA function during pregnancy with good repeatability.

Gestational diabetes mellitus (GDM) is a common cause of maternal morbidity, and can lead to the development of diabetes later in life. Pre-pregnancy body weight is associated with the change in body mass index (BMI) between a first and second pregnancy. Compared with long-term change in BMI between pregnancies, the most accessible follow-up point to investigate BMI change is 6 weeks after the initial pregnancy. The present study aimed to assess the association between weight retention at 6 weeks postpartum and the risk of GDM in a subsequent pregnancy. We recruited 6429 singleton pregnancies into this retrospective cohort study. For each pregnancy, we calculated weight retention at 6 weeks postpartum after the first pregnancy, the interpregnancy BMI change between pregnancies, and the gestational weight gain in the second pregnancy. Risk was represented by the odds ratio (OR) and 95% confidence intervals (CIs). We then determined the relationship between postpartum weight retention at 6 weeks after the initial pregnancy, and the interpregnancy change in BMI between pregnancies. Analyses were stratified by BMI during the first pregnancy. Compared to women with a stable BMI (− 1 to 1), interpregnancy BMI gains were associated with an increased risk of GDM in the second pregnancy. Risk increased significantly for women with a BMI below and above 25 during the first pregnancy, although the increase was greater in the women with a BMI < 25. The risk of GDM in the second pregnancy was higher in women with inadequate weight gain during the second gestation. The weight retention at 6 weeks postpartum, where there was a gain of > 3 BMI units was significantly more related to weight gain more than when there was 1 BMI unit gain between pregnancies (P < 0.05) and associated with an increased incidence of GDM in the second pregnancy (OR = 2.95, 95% CI: 1.95 ~ 4.45). Women who showed a change in BMI that was > 3 units at 6 weeks postpartum after the first pregnancy showed an increased risk for BMI subsequently (OR = 1.42, 95% CI: 1.08~1.87). Women who gained more than 3 BMI units at 6 weeks postpartum were associated with an increased risk of BMI in a subsequent pregnancy. Six weeks postpartum provides a new early window of opportunity to identify risk factors for a subsequent pregnancy and allows us to implement primary prevention strategies.