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Abstract Background Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6–12 h after symptom onset is effective and safe in these patients is unknown. Methods A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6–12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0–1 at 90 days) was estimated using multivariable logistic regression analysis. Results A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P

Abstract Background Chronic gastritis has been demonstrated to be a key cause of gastric cancer (GC), and control of gastric inflammation is regarded as an effective treatment for the clinical prevention of gastric carcinogenesis. However, there remains an unmet need to identify the dominant regulators of gastric oncogenesis-associated inflammation in vivo. Methods The mouse model for the study of inflammation-associated GC was induced by Benzo[a]pyrene (BaP) intragastric administration in Bcl6b −/− and wildtype mice on a C57BL/6 background. 5-Aza-2′-deoxycytidine (5-Aza), the demethylation drug, was intraperitoneally injected to restore Bcl6b expression. Human GC tissue array was used to analyse patient survival based on BCL6B and CD3 protein expression. Results Bcl6b was gradually downregulated by its own promoter hypermethylation in parallel to an increasing inflammatory response during the progression of BaP-induced gastric carcinogenesis in mice. Moreover, knockout of Bcl6b dramatically worsened the severity of gastric cancer and aggravated the inflammatory response in the BaP-induced mice GC model. Re-activation of Bcl6b by 5-Aza impeded inflammatory amplification and BaP-induced GC development, prolonging survival time in wildtype mice, whereas no notable curative effect occurred in Bcl6b −/− mice with 5-Aza treatment. Finally, significant negative correlations were detected between the mRNA levels of BCL6B and inflammatory cytokines in human GC tissues; patients harbouring BCL6B-negetive and severe-inflammation GC tumours were found to exhibit the shortest survival time. Conclusions Epigenetic inactivation of Bcl6b promotes gastric cancer through amplification of the gastric inflammatory response in vivo and offers a new approach for GC treatment and regenerative medicine.

Abstract Conventional tumor markers for non-invasive diagnosis of gastric cancer (GC) exhibit insufficient sensitivity and specificity to facilitate detection of early gastric cancer (EGC). We aimed to identify EGC-specific exosomal lncRNA biomarkers that are highly sensitive and stable for the non-invasive diagnosis of EGC. Hence, in the present study, exosomes from the plasma of five healthy individuals and ten stage I GC patients and from culture media of four human primary stomach epithelial cells and four gastric cancer cells (GCCs) were isolated. Exosomal RNA profiling was performed using RNA sequencing to identify EGC-specific exosomal lncRNAs. A total of 79 and 285 exosomal RNAs were expressed at significantly higher levels in stage I GC patients and GCCs, respectively, than that in normal controls. Through combinational analysis of the RNA sequencing results, we found two EGC-specific exosomal lncRNAs, lncUEGC1 and lncUEGC2, which were further confirmed to be remarkably up-regulated in exosomes derived from EGC patients and GCCs. Furthermore, stability testing demonstrates that almost all the plasma lncUEGC1 was encapsulated within exosomes and thus protected from RNase degradation. The diagnostic accuracy of exosomal lncUEGC1 was evaluated, and lncUEGC1 exhibited AUC values of 0.8760 and 0.8406 in discriminating EGC patients from healthy individuals and those with premalignant chronic atrophic gastritis, respectively, which was higher than the diagnostic accuracy of carcinoembryonic antigen. Consequently, exosomal lncUEGC1 may be promising in the development of highly sensitive, stable, and non-invasive biomarkers for EGC diagnosis.

Abstract Background The present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China. Methods Four hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes. Their mutation difference was analyzed by SNaP shot techniques. GeneMapper4.1 SPSS20.0 software was used for data management and analysis. Using a single locus analysis, the distribution difference of genotype loci in ischemic stroke cases and controls were detected to assess the genetic risk factors of ischemic stroke. Results Significance differences of genotype distribution in ischemic stroke cases and controls were observed in LDLR rs688 in Han and Uighur population in recessive model from analysis of single gene locus. It also was found that dramatic difference of triglyceride (TG) of LPL rs328 and systolic blood pressure in CETP rs708277 of total population. In binary logistic regression analysis of total studied population, ischemic stroke was observed significantly associated with LDLR rs688 both addictive model (TT/CC, adjusted OR = 1.47, 95% CI = 1.04–2.07) and recessive model (TT/CT + CC, adjusted Odds ratio (OR) = 2.66, 95% Confidence Interval (CI) = 1.37–5.14). In Han population, ischemic stroke was observed significantly associated with rs688 both in addictive model (TT/CC, adjusted OR = 3.27, 95% CI = 1.06–10.05). In Uighur population, no significant association was found between gene polymorphisms and the risk of ischemic stroke. Combined analysis of multiple gene and loci, interaction effects of LDLR rs688 C/T, ApoA5 rs662799 A/G and CETP rs708272 C/T denoted a significant influence on IS susceptibility. Conclusion Single nucleotide polymorphisms of lipid metabolism relative gene were significantly associated with the morbidity of ischemic stroke in Han population. The interaction effects of rs688 C/T with ApoA5 rs662799 A/G and CETP rs708272 C/T promoted the occurrence of IS.