Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa

AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China

Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether mitochondrial DNA(mtDNA)variants,which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production,are associated with COVID-19 risk.Methods:A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls(n=615)and COVID-19 patients(n=536).COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning.The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment.MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny.Student’s t-test was used for continuous variables,and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables.To assess the independent effect of each mtDNA variant defining mtDNA haplogroups,multivariate logistic regression analyses were performed to calculate the odds ratios(OR)and 95%confidence intervals(CI)with adjustments for possible confounding factors of age,sex,smoking and diseases(including cardiopulmonary diseases,diabetes,obesity and hypertension)as determined through clinical and radiographic examinations.Results:Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations(>10%in the control population)at C5178 a(in NADH dehydrogenase subunit 2 gene,ND2)and A249 d(in the displacement loop region,D-loop)/T6392 C(in cytochrome c oxidase I gene,CO1)/G10310 A(in ND3)were associated with a reduced risk of severe COVID-19(OR=0.590,95%CI 0.428–0.814,P=0.001;and OR=0.654,95%CI 0.457–0.936,P=0.020,respectively),while A4833 G(ND2),A4715 G(ND2),T3394 C(ND1)and G5417 A(ND2)/C16257 a(D-loop)/C16261 T(D-loop)were related to an increased risk of severe COVID-19(OR=2.336,95%CI 1.179–4.608,P=0.015;OR=2.033,95%CI 1.242–3.322,P=0.005;OR=3.040,95%CI 1.522–6.061,P=0.002;and OR=2.890,95%CI 1.199–6.993,P=0.018,respectively).Conclusions:This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19.Based on the case–control study,we concluded that the common mtDNA variants at C5178 a and A249 d/T6392 C/G10310 A might contribute to an individual’s resistance to developing severe COVID-19,whereas A4833 G,A4715 G,T3394 C and G5417 A/C16257 a/C16261 T might increase an individual’s risk of developing severe COVID-19.

In inflammatory bowel disease and extraintestinal manifestations:What role does microbiome play?

Inflammatory bowel disease(IBD)is a systemic disorder affecting intestinal tract and other organs outside the gut,known as extraintestinal manifestations(EIMs).These EIMs are complex and diverse,and early treatment may reduce teratogenic rates and improve quality of life.However,our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight.Fortunately,advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs.The gut microbiota can drive aberrant immune activation and intestinal inflammation.Intriguingly,chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis.Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function.Furthermore,gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites,leading to systemic inflammatory responses.The microbiome is showing its potential in treating IBD and EIMs,and microbial engineering approaches,such as probiotic engineering and engineered fecal microbiota transplantation,are exhibiting great promise for IBD therapeutics.