MAPKAP kinase 2 (MK2)-dependent and independent models of blister formation in pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by autoantibodies to the keratinocyte adhesion protein desmoglein (Dsg) 3. Previous studies suggest that PV pathogenesis involves p38 mitogen activated protein kinase-dependent and -independent pathways. However, p38 is a difficult protein to study and therapeutically target because it has four isoforms and multiple downstream effectors. In the current study, we identify MAPKAP kinase 2 (MK2) as a downstream effector of p38 signaling in PV and describe MK2-dependent and -independent mechanisms of blister formation using passive transfer of human anti-Dsg IgG4 mAbs to neonatal mice. In human keratinocytes, PV mAbs activate MK2 in a dose-dependent manner. MK2 is also activated in human pemphigus skin blisters, causing translocation of MK2 from the nucleus to the cytosol. Small molecule inhibition of MK2 and silencing of MK2 expression block PV mAb-induced Dsg3 endocytosis in human keratinocytes. Additionally, small molecule inhibition and genetic deletion of p38α and MK2 inhibit spontaneous, but not induced, suprabasal blisters by PV mAbs in mouse passive transfer models. Collectively, these data suggest that MK2 is a key downstream effector of p38 that can modulate PV autoantibody pathogenicity. MK2 inhibition may be a valuable adjunctive therapy for control of pemphigus blistering

Association between alcohol consumption during pregnancy and risks of congenital heart defects in offspring: Meta-analysis of epidemiological observational studies

BACKGROUND: To explore the association between maternal alcohol consumption and/or binge drinking and congenital heart defects (CHDs), we conducted a meta-analysis for more sufficient evidence on this issue. METHODS: We searched Medline, EMBASE, and the Cochrane Library from their inceptions to December 2014 for case-control and cohort studies that assessed the association between maternal alcohol consumption and CHD risk. Study-specific relative risk estimates were calculated using random-effect or fixed-effect models. RESULTS: A total of 19 case-control studies and 4 cohort studies were included in the meta-analysis. We observed a null association between maternal alcohol consumption during pregnancy and the risk of CHDs. Even in the analysis of different trimesters of pregnancy, we found little association between the two. CONCLUSIONS: This meta-analysis suggests that maternal alcohol consumption is modestly not associated with the risk of CHDs. However, further investigation is needed to confirm this conclusion

Attenuating Immune Response of Macrophage by Enhancing Hydrophilicity of Ti Surface

Immune responses can determine the in vivo fate of implanted materials. The strategy for developing implants has shifted towards using materials with immunomodulatory activity. However, the immunoregulatory effect of hydrophilicity of titanium surface on the macrophage behavior and its underlying mechanism remain poorly understood. Here, the Ti surface hydrophilicity-dependent behavior of murine RAW264.7 macrophages was investigated in vitro. Two laboratory models with significantly different surface hydrophilicity and similar roughness were established with Ti-polished and Ti-H2O2 surfaces. The results of cell morphology observation showed that the Ti-H2O2 surface yielded enhanced cell adhesion and less multinucleated cell formation. CCK-8 assay indicated that the growth rate of macrophage on Ti-H2O2 surface is higher than that of Ti-polished. ELISA assay result revealed lower level of proinflammatory factor TNF-α and higher level of anti-inflammatory factor IL-10 on the Ti-H2O2 surface compared to Ti-polished. Subsequently, immunofluorescence and western blotting analysis showed that activation of the NF-κB-TNF-α pathway might be involved in the modulation of the immune response by surface hydrophilicity. Together, these results suggested that relative high hydrophilic Ti surface might attenuate the immune response of macrophage by activating NF-κB signaling. These findings could provide new insights into designing implant devices for orthopedic applications

Percutaneous Punctured Transcatheter Device Closure of Residual Shunt after Ventricular Septal Defect Repair

Ventricular septal defects (VSDs) are estimated to account for 20 to 30% of all congenital heart defects (CHDs). Although a residual shunt is the most common complication of VSD surgery, a second operation that applies the surgical repair method is very difficult because it can increase the possibility of uncontrolled bleeding and the severity of tissue adhesion. Here, we present the first case of percutaneous punctured transcatheter device closure of a residual shunt after VSD repair as a novel method to further develop for the treatment of children with congenital heart disease

MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies

Abstract Background Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in the hyperhomocysteinemia, which is a risk factor related to the occurrence of congenital heart defect (CHD). However, the association between MTHFR polymorphism and CHD has been inconclusive. Methods We conducted an updated meta-analysis to provide comprehensive evidence on the role of MTHFR A1298C polymorphism in CHD. Databases were searched and a total of 16 studies containing 2207 cases and 2364 controls were included. Results We detected that a significant association was found in the recessive model (CC vs. AA + AC: OR = 1.38, 95% CI: 1.10–1.73) for the overall population. Subgroup analysis showed that associations were found in patients without Down Syndrome in genetic models for CC vs. AA (OR = 1.47, 95% CI: 1.01–2.14), CC vs. AC (OR = 1.29, 95% CI: 1.00–1.66) and recessive model (OR = 1.44, 95% CI: 1.14–1.82). We conducted a meta-regression analysis, Galbraith plots and a sensitivity analysis to assess the sources of heterogeneity. Conclusions In summary, our present meta-analysis supports the MTHFR 1298C allele as a risk factor for CHD. However, further studies should be conducted to investigate the correlation of plasma homocysteine levels, enzyme activity, and periconceptional folic acid supplementation with the risk of CHD

Reduction in the duration of postoperative fever following NUSS surgery during the COVID-19 pandemic

Abstract Background Our study aimed to compare the prevalence of postoperative fever during the COVID-19 pandemic period with that of the preceding non-pandemic period. Methods A retrospective analysis was conducted on patients with pectus excavatum (PE) undergoing minimally invasive repair (also called NUSS procedure) at Nanjing Children’s Hospital from January 1, 2017 to March 1, 2019 (Group 2019), and from January 1, 2020 to March 1, 2021 (Group 2021). Data from a total of 284 patients, consisting of 200 (70.4%) males and 84 (29.6%) females with an average age of 9.73 ± 3.41 (range, 4 to 17) years, were collected. The presence of post-operative fever (defined as a forehead temperature of 37.5℃ or above within 72 h post-surgery), as well as the time of operation, duration of postoperative mechanical ventilator and urinary catheter use, and length of hospitalization were all assessed in admitted patients from Group 2019 (n = 144) and Group 2021 (n = 140). Postoperative white blood cell (WBC), C-reactive protein (CRP) levels, and prevalence of postoperative complications (i.e., pneumothorax, pulmonary atelectasis, pneumonia, wound infection, and dehiscence) were also determined. Result Our results showed a statistically significant decrease in the incidence of postoperative fever within 24 to 72 h of surgery in patients admitted from Group 2019 as compared to Group 2021 (p  0.05). The average hospitalization length of Group 2021 was significantly shorter than Group 2019 (12.49 ± 2.57 vs. 11.85 ± 2.19 days, p  0.05). Conclusion The prevalence of postoperative fever within 72 h of surgery and the length of hospital stay for patients with PE undergoing NUSS surgery were both decreased in Group 2021. We propose that the above phenomenon may be related to increased used of personal protection equipment (such as surgical masks and filtering facepiece respirators (FFRs)) by physicians, nurses, and the patients themselves