Immune response to Helicobacter pylori infection and gastric cancer development

Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.     

A genetic interaction of NRXN2 with GABRE,SYT1 and CASK in migraine patients: a case-control study

BackgroundMigraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles.Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility.MethodsA case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ² test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0.ResultsWe found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76–12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325''s GG genotype and rs2998250’s CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01–0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility.ConclusionsThis study unravels, for the first time, the gene-gene interactions between NRXN2, GABRE - a GABA_A-receptor - and CASK, importantly it shows the synergetic effect between those genes and its relation with migraine susceptibility.These gene interactions, which may be a part of a larger network, can potentially help us in better understanding migraine aetiology and in development of new therapeutic approaches.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01266-y.     

慢性移植肾失功后的移植肾切除手术分析

目的:分析总结因慢性移植肾失功而行移植肾切除手术患者的临床治疗经过,进一步探讨这类手术的安全性和适应证。方法:以慢性移植肾失功患者76例为研究对象,年龄23~72(36.6±13.5)岁,以上患者发生慢性移植肾失功的时间为术后11~91(35.8±24.6)个月,转入血液透析的时间为3~33(10.4±6.2)个月。76例患者均实施了移植肾切除手术,移植肾切除术后随访时间为6个月~5年。结果:平均手术时间50(35~180)min;术中平均出血量450(200~2 600)ml,平均输血量300(400~2 400)ml,其中67例进行了自体血液回收后输血。术后平均引流量250(20~1 100)ml,平均住院时间11(5~23)d。术后主要并发症:切口血肿8例,切口感染10例,消化道出血7例,心衰7例,肺部感染5例,肾上腺危象2例,下肢跛行2例。死亡4例。多数患者的体重指数、血红蛋白及血清白蛋白含量较术前有所提高。结论:慢性移植肾失功后的移植肾切除手术为高风险手术,应积极做好术前准备,同时加强围手术期护理,以降低手术并发症的发生率;积极适时地切除已经完全失功了的移植肾,有助于改善患者身体素质,避免免疫抑制的不良反应,同时有利于减轻患者本人及社会的经济负担。     

Purification of hemopoietic progenitor cells from human marrow using a fucose-binding lectin and cell sorting

Human peripheral blood granulocytes, but not lymphocytes, erythrocytes, or monocytes, bound the fucose-binding lectin from Lotus tetragonolobus (FBP), and this binding was competitively inhibited by the sugar alpha- L-fucose. The fluorescence-activated cell sorter was used to study the appearance of this receptor on human marrow cells during granulocyte differentiation and to prepare fractions enriched for granulocyte- macrophage progenitor cells (granulocyte-macrophage colony-forming cells--GM-CFC). Cell binding of fluoresceinated FBP increased for bone marrow cells in the sequence--lymphocytes, blast cells, promyelocytes and myelocytes, monocytes, and polymorphonuclear cells. Selection of cells with appropriate low-angle or high-angle light scatter characteristics achieved a 10-fold or 2-3-fold enrichment of progenitor cells, respectively. By selecting cells with intermediate fluorescence intensity, a further 2-3-fold enrichment for GM-CFC was obtained. Cell sorting using the optimal selection of these three parameters produced up to 36-fold enrichment of the progenitor cells from human bone marrow. The most enriched fraction was composed of 23% progenitor cells (colony- and cluster-forming cells) with a yield of 36%. In populations most highly enriched by GM-CFC, immature cells (blast cells, promyelocytes, and myelocytes) made up 95% of the cells present.     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.     

Sebaceous carcinoma of the lip: Comparing normal lip and cheek anatomy with the imaging features of a rare cutaneous malignancy

Sebaceous carcinoma is a rare cutaneous malignancy, commonly affecting the eyelids. This case highlights a patient who presented with sebaceous carcinoma of the right upper lip with extensive involvement of the soft tissues of the head and neck. As part of the initial investigation, ultrasound was requested. This case demonstrates the ultrasound features of sebaceous carcinoma as well as revising the normal ultrasound anatomy of the upper lip and muscles of the cheek.