The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.

BACKGROUNDOver the last decade, Clostridium difficile infection (CDI) has emerged as a significant nosocomial infection, yet little has been reported from China. This study aimed to characterize the clinical and microbiological features of CDI from a hospital in Shanghai.

METHODSPatients with CDI seen between December 2010 and March 2013 were included in this study, of which clinical data were retrospectively collected. The microbiological features of corresponding isolates were analyzed including genotype by multi-locus sequence typing (MLST), antimicrobial susceptibility, toxin production, sporulation capacity, biofilm formation, and motility.

RESULTSNinety-four cases of CDI were included during this study period, 12 of whom were severe cases. By reviewing the clinical data, all patients were treated empirically with proton pump inhibitor or antibiotics or both, and they were distributed widely across various wards, most frequently to the digestive ward (28/94, 29.79%). Comparing the severe with mild cases, no significant differences were found in the basic epidemiological data or the microbiological features. Among the 94 isolates, 31 were toxin A-negative toxin B-positive all genotyped as ST37. They generated fewer toxins and spores, as well as similar amounts of biofilm and motility percentages, but exhibited highest drug resistance to cephalosporins, quinolones, macrolide-lincosamide and streptogramin (MLSB), and tetracycline.

CONCLUSIONSNo specific clinical genotype or microbiological features were found in severe cases; antimicrobial resistance could be the primary reason for epidemic strains leading to the dissemination and persistence of CDI.

Anti-Bacterial Agents ; pharmacology ; Biofilms ; drug effects ; Cephalosporins ; pharmacology ; China ; Clostridium difficile ; drug effects ; genetics ; isolation & purification ; Genotype ; Multilocus Sequence Typing ; methods ; Quinolones ; pharmacology ; Tertiary Healthcare ; statistics & numerical data ; Tetracycline ; pharmacology

Objective To investigate the activation of nuclear factor-B (NF-B)and hypoxia-inducible factor-1 (HIF-1)in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Subjects were classified into mild-to-moderate OSHAS group (n = 16), severe OSAHS group (n = 14) and the matched control group (n=30). Gene and protein expressions of NF-B and HIF-1 were measured by RT-PCR, Western blot in peripheral blood mononuclear cells (PBMC). Results NF-κB p65 mRNA and NF-κB p65 protein,HIF-1α mRNA and HIF-1α protein in PBMC were significantly higher in severe OSAHS group than those in mild–to-moderate group and control group (P<0.01). But there were no significant difference in NF-κB p65 mRNA and NF-κB p65 protein between mild-to-moderate group and control group (P=0.068, P=0.254 respectively). Only gene (P<0.05) not the protein (P=0.777) of HIF-1αwas higher in mild-to-moderate as compared with control group. Both NF-κB p65 mRNA and HIF-1αmRNA were positively correlated with AHI (r=0.493, P=0.006, r=0.508, P=0.004), while negatively correlated with nighttime lowest blood oxygen saturation (LSaO2)(r=-0.488, P=0.006, r=-0.46, P=0.011). There was a positive correlation between NF-κB p65 protein level and AHI (r=0.669, P<0.001). HIF-1αprotein level was positively correlated with AHI, ODI (r=0.628, P=0.001;r=0.480, P=0.018). There were positive correlations between NF-κBp65mRNA and HIF-1αmRNA (r=0.543, P=0.002), NF-κBp65 and HIF-1αprotein respectively (r=0.716, P<0.001). Conclusions As the gene and protein of NF-κB and HIF-1 were up-regulated in patients with OSAHS, and also positively correlated with the severity of sickness. We conclude that both NF-κB and HIF-1 were involed in the pathogenesis of OSAHS.

Objective To evaluate the influence of nuclear factor (NF)-κB activation in peripheral blood mononuclear cells (PBMCs) on vascular inflammation in elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods The 40 elderly subjects (≥65years old) were classed into control, mild, moderate and severe groups (n = 10, respectively)according to polysomnography (PSG). After PSG, the samples of peripheral venous blood were collected, and PBMCs were isolated. Nuclear protein was extracted and NF-κB was measured by Western blotting. ELISA was applied to measure the levels of TNF-α and IL-6 in serum. Blood samples from 10 cases (moderate 5 and severe 5) were measured again after four weeks of continuous positive airway pressure (CPAP) treatment. Results The expression of NF-κB in PBMCs and the concentration of TNF-α in serum were significantly increased in severe and moderate OSAHS patients compared with controls (P＜0. 05). The NF-κB expression was positively correlated with AHI (r=0. 617, P＜ 0. 001) and TNF-α concentration (r = 0. 498, P＜ 0. 001 ), negatively correlated with LSaO2 (r= -0. 548, P＜0. 001), and not correlated with IL-6 concentration (r=0. 365, P=0. 201).The CPAP treatment could significantly inhibit NF-κB activation in PBMCs and reduce TNF-αexcretion (P＜0.05, respectively). Conclusions PBMCs may play an important role in vascular endothelial injury through NF-κB expression and TNF-α excretion in elderly OSAHS patients, which is closely associated with the severity of the syndrome and night hypoxemia. CPAP treatment can inhibit the pathophysiologic process effectively.

Objective To evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) and its characteristics in elderly patients with cardiovascular diseases, and provide reference for the clinical decisions. Methods All patients who were hospitalized in department of cardiovascular medicine from January to June in 2007 were invited to participate in the current study. A total of 317 hospitalized elderly patients were recruited into this study. All participants were assessed by portable bedside nocturnal polysomnograph and Epworth sleepiness scale (ESS). Results Among 317 patients, 281 cases (88.6%) met the criterion of obstructive sleep apnea (OSA) [apnea and hypopnea index (AHI)≥5] and 47 cases (14.8%) met the criteria of obstructive sleep apnea syndrome (OSAS) (AHI≥5 and ESS≥9). When the severity of OSA (as indicated by AHI) was considered as a dependent variable, multiple regression analysis indicated that it was significantly associated with minimal SaO2 and the oxygen desaturation index, while age, habitual snoring, ESS, BMI, mean SaO2 and the duration of SaO2≤ 90% did not show significant effects on the severity of OSA. Conclusions High prevalence of obstructive sleep apnea syndrome (with daytime sleepiness) is found in elderly hospitalized patients and the rate of obstructive sleep apnea is much higher in patients without daytime sleepiness symptoms. Minimal SaO2 and the oxygen desaturation index are the important predicting factors for the severity of OSA, while age, BMI, habitual snoring, sleepiness are not correlated with the severity of OSA after adjusting minimal SaO2 and oxygen desaturation index.