Assessment of Endothelial Dysfunction in Patients with Kawasaki Disease: A Meta-Analysis.

Background: Kawasaki disease (KD) is a well-known systemic inflammatory vasculitis. Endothelial dysfunction is one of most easily overlooked non-coronary complications of KD. Several studies have assessed endothelial dysfunction using flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD), and biomarkers (E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1)). However, the results were inconsistent and incomplete. Methods: We searched five databases for eligible studies until March 8, 2022. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for FMD, NMD, and four biomarkers level between KD and healthy children. A meta-analysis with subgroup analysis was conducted. Results: 40 studies with a total of 2670 children (1665 KD patients and 1005 healthy children) were identified. During the acute phase, KD patients had lower FMD compared to the control group (WMD = -10.39, 95% CI: -13.80- -6.98). During the subacute phase, KD patients had lower FMD compared to the control group (WMD = -15.07, 95% CI: -17.61- -12.52). During the convalescence phase, KD patients had lower FMD and similar NMD compared to the control group (WMD = -4.95, 95% CI: -6.32- -3.58; WMD = -0.92, 95% CI: -2.39-0.55, respectively). During the convalescence phase, those KD patients without coronary artery lesion (CAL), with CAL, even with coronary artery aneurysm, had progressively lower FMD compared to healthy children (WMD = -3.82, 95% CI: -7.30- -0.34; WMD = -6.32, 95% CI: -7.60- -5.04; and WMD = -6.97, 95% CI: -7.99- -5.95, respectively). Compared to KD patients without CAL, those with CAL had lower FMD (WMD = -1.65, 95% CI: -2.92- -0.37). KD patients had higher levels of E-selectin, P-selectin, and ICAM-1 compared to healthy controls during different phases. KD patients had a higher level of VCAM-1 compared to healthy controls only during the acute phase (WMD = 61.62, 95% CI: 21.38-101.86). Conclusions: Endothelial dysfunction is present since the onset of KD and persists for years, confirmed by the measurement of FMD and biomarkers from different phases. An assumption is advanced that FMD impairment (the severity of endothelial dysfunction) may be positively correlated with CAL severity during the convalescence phase.

Outpatient cervical ripening with balloon catheters: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: One in four labors are induced. The process of cervical ripening can be lengthy and pre-labor hospitalization is required. Outpatient cervical ripening can be an attractive alternative. OBJECTIVES: To evaluate the efficacy and safety of outpatient cervical ripening with a balloon catheter compared with inpatient balloon catheter or prostaglandin E2 (PGE2). SEARCH STRATEGY: The PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases were searched from their inception to October 15, 2022. SELECTION CRITERIA: Randomized controlled trials comparing the outpatient balloon catheter with inpatient balloon catheter or inpatient PGE2 for term cervical ripening. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis was performed. The primary outcome was the cesarean delivery rate. The secondary outcomes included instrumental delivery, the time from intervention-to-birth, oxytocin augmentation, total hospital duration, and maternal/neonatal adverse events. MAIN RESULTS: Twenty-nine randomized controlled trials with a total of 6004 participants were identified. No difference in the cesarean delivery rate was revealed among the three interventions. Compared with inpatient balloon catheter, outpatient balloon catheter had shorter total hospital duration (mean difference -8.58, 95% confidence interval -17.02 to -1.10). No differences were revealed in the time from intervention-to-birth, instrumental delivery, postpartum hemorrhage, 5-min Apgar score less than 7, umbilical cord arterial pH less than 7.1, and neonatal intensive care unit admission among the three interventions. CONCLUSIONS: Outpatient balloon catheter in low-risk term pregnancies is an available option that could be considered for cervical ripening. The safety and effectiveness are comparable to inpatient cervical ripening methods.

Assisted reproductive technologies and postpartum depressive symptoms: A meta-analysis.

BACKGROUND: Assisted reproductive technologies (ARTs) have become the main treatment for infertility. ART treatment can be a stressful life event for infertile females. Whether there is an association between ARTs and postpartum depressive symptoms (PDS) has not been established. METHODS: PubMed, MEDLINE, EMBASE, PsycINFO, and CNKI were searched. The pooled outcome was the difference in incidence of PDS within 1 year postpartum between ARTs and the spontaneous pregnancy group. RESULTS: A total of 12 cohort studies, which were conducted in eight developed countries and two developing countries, were involved. In total, 106,338 pregnant women, including 4990 infertile females with ARTs treatment and 101,348 women with spontaneous pregnancy, were enrolled in our final analysis. ARTs women had a lower incidence of PDS compared to the spontaneous pregnancy group according to a random effect model (OR = 0.83, 95 % CI: 0.71-0.97, p = 0.022, I2 = 62.0 %). Subgroup analyses indicated that studies on late PDS (follow-up: 3-12 months postpartum) were more heterogeneous than those on early PDS (follow-up: <3 months postpartum) (I2 = 24.3 % vs. I2 = 0 %, interaction p-value < 0.001). There was a strong relationship between ARTs and late PDS (OR = 0.65, 95 % CI: 0.55-0.77, p < 0.001). Therefore, the possible source of heterogeneity was the postpartum evaluation time, which was confirmed by post-hoc meta-regression. LIMITATIONS: Some underlying confounders, such as previous psychiatric illness, the limited availability of ARTs, and ethnic disparities, cannot be ignored and may have biased interpretation of the results. CONCLUSION: The available data suggested that ARTs were associated with lower incidence of PDS, especially when follow-up lasted over 3 months. However, these findings should be interpreted with caution. Better-designed trials are needed to confirm this association.

Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral.

BACKGROUND: Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. MATERIAL AND METHODS: Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (µCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1ß, IL-4). RESULTS: Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1ß levels, and less active MMP-9 in cell culture. CONCLUSION: This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

Analysis of ventricular-vascular properties during preeclampsia: an echocardiography study.

The aim of the study is to analyze ventricular-vascular properties with different ventricular-arterial coupling (VAC) ratio in the preeclamptic women. Seventy-seven pregnant women with preeclampsia and eighty-nine with normal pregnancy were performed echocardiography. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees). Using the VAC value of 0.8 as the cut-off near uncoupling, the preeclampsia cases were divided into two subgroups: VAC ratio ≥ 0.8 and <0.8. Cardiac structure and function, VAC properties, as well as four components of the LV pressure-strain loop, including global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were determined. The preeclampsia with VAC ≥ 0.8 had an enlarger indexed ventricular volume and a thicker relative ventricular wall than the VAC < 0.8. The Ees significantly increased in the subgroup with VAC < 0.8 and decreased in the VAC ≥ 0.8, while the Ea increased in both of them. The preeclampsia with VAC ≥ 0.8 showed an obvious augmentation in GWI, GCW and GWE, along with a similar GWW compared to those with VAC < 0.8. There were variable relationships between the LV pressure-strain components and VAC properties. Thus, the preeclampsia with VAC ≥ 0.8 undergoes a more adverse remodeling and a greater impact on cardiac contractility. The increased stiffness of the heart and arterial system, and increased resistance of peripheral vessels net lead to the deteriorative ventricular efficiency with elevated myocardial oxygen consumption during a preeclampsia pregnancy.

Development of an XBP1 agonist, HLJ2, as a potential therapeutic agent for ulcerative colitis / 中国药理学与毒理学杂志

OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myelo?peroxidase(MPO) activity and reduced production of the inflammatory cytokines TNF- α, IL- 1β, andIL- 6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demon?strated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microor?ganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2- treated mice compared with untreated mice. CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.

Sensitivity to bortezomib of RPIM8226 cells after co-cultured with down-regulated Cav-1 expression HUVECs / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity to bortezomib of RPMI8226 cells after co-cultured with down-regulated Caveolin (Cav)-1 expression of HUVECs by transfection with Cav-1 shRNA (HUVECs(Cav-1 low)).</p><p><b>METHODS</b>Exposure to bortezomib with or without 50 nmol/L dexamethasone at different concentration, the proliferation of RPMI8226 was analyzed by MTT assay when it was cultured alone or co-cultured with HUVECs(Cav-1 low). Cav-1 expression was detected by using of Western blot and cell cycle, apoptosis and the level of reactive oxygen species (ROS) were analyzed by flow cytometry.</p><p><b>RESULTS</b>Cav-1 expression was notably down-regulated in HUVECs(Cav-1 low) (0.2199±0.0288 vs 1.3195±0.2393) (P<0.01). The IC(50) of bortezomib for RPMI8226 cultured alone, co-cultured with HUVECs orHUVECCav- 1 low were 20 nmol/L, 50 nmol/L and 65 nmol/L, respectively. The percentages of G₀/G₁ phase in RPMI8226 cultured alone, co-cultured with HUVECs and HUVECs(Cav-1 low) were 28.49%, 30.41%, and 36.15% respectively. The protection of RPMI 8226 against apoptosis by HUVECs was demonstrated that the apoptosis/death rates were 66.8%, 10.7% and 8.6% in RPMI8226 cultured alone, co-cultured with HUVECs and HUVECs(Cav-1 low) after exposure to 20 nmol/L bortezomib for 24 h. RPMI8226 could induce the oxidative stress of HUVECs before and after co-culture. The ROS level was raised from 15.0% to 35.2% in RPMI8226, from 80.4% to 91.0% in HUVECs, and from 84.6% to 96.8% in HUVECs(Cav-1 low).</p><p><b>CONCLUSION</b>The down-regulated Cav-1 expression of HUVECs could promote proliferation and induce apoptosis of RMPI8226 cells, lead to G₀/G₁ phase arrest, and reduce the sensitivity to bortezomib.</p>

Endogenous neuregulin-1 expression in the anterior pituitary of female Wistar-Furth rats during the estrous cycle / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the changes in endogenous neuregulin-1 (Nrg1) expression in the anterior pituitary of female Wistar-Furth rats in different phases of the estrous cycle.</p><p><b>METHODS</b>Female Wistar-Furth rats during estrous cycles were used. RT-PCR was employed to study the changes in the expression of Nrg1 isoforms and their cognate receptors ErbB-2 and ErbB-4 in the anterior pituitary in different phases of the estrous cycle. Western blotting was used to detect Nrg1 expression at the protein level. Immunofluorescence staining was used to identify hypophyseal cells expressing Nrg1 and observe the localization and distribution of Nrg1 and functional phosphorylation of ErbB-4. The co-expression of Nrg1 and ErbB-4 in the anterior pituitary of Rhesus monkey was also investigated.</p><p><b>RESULTS</b>Some of the Nrg1 isoforms, especially type III Nrg1s, were expressed at a higher level during the estrous cycle I (E1) and estrous cycle II (E2), a result consistent with that of Western blotting for samples of the anterior pituitaries collected at these phases. Immunofluorescence staining identified the gonadotrophs as the main source of Nrg1, and showed an extensive distribution of Nrg1 in the anterior pituitary in E1 and E2 phases accompanied by apparent phosphorylated activation of ErbB-4. Adjacent distribution of Nrg1- and ErbB-4-positive cells was also observed in the anterior pituitary of male Rhesus monkeys.</p><p><b>CONCLUSION</b>Our results provide evidence for the expression of multiple Nrg1 isoforms and the presence of Nrg1/ErbB-4 signaling in the anterior pituitary of female Wistar-Furth rats. This signaling demonstrates an estrous cycle phase-related pattern. Additionally, Nrg1/ErbB-4-based juxtacrine signaling may exist in the anterior pituitary of male non-human primate.</p>

Glucagon receptor is required for long-term survival: A natural history study of the Mahvash disease in a murine model

Background and aim We have described a novel Mahvash disease of hyperglucagonemia and pancreatic neuroendocrine tumors (PNETs) associated with an inactivating glucagon receptor mutation, and identified the glucagon receptor-deficient (..) (AU)

Antecedentes y objetivo: Hemos descrito la nueva enfermedad de Mahvash en la que existen hiperglucagonemia y tumores neuroendocrinos pancreáticos (TNEP) asociados con una mutación inactivante del receptor de glucagón, e (..) (AU)