Association between circadian syndrome and chronic diarrhea: a cross-sectional study of NHANES 2005-2010 data.

Background: Circadian rhythms are reported to influence physiological processes in the gastrointestinal system, but associations between circadian syndrome (Circs) and chronic diarrhea (CD) remain unclear. Here, we explored such relationships to provide new insights into CD management. Methods: We conducted a cross-sectional retrospective analysis using the National Health and Nutrition Examination Survey (NHANES) data between 2005 and 2010. Univariate and multivariable logistic regression analyses were performed on weighted data to explore associations between Circs and CD. Results: Results were presented using forest plots, odds ratios (ORs), and 95% confidence intervals (CIs). Data with p-values < 0.05 were considered statistically significant. In total, 5,661 US participants, of which 412 had CD (weighted percentage = 6.20%), were enrolled. In univariate logistic regression analyses, participants with Circs had a significantly higher risk of CD (OR = 1.51, 95% CI: 1.15-1.99). After adjusting for covariates, model 2 (OR = 1.40, 95% CI: 1.03-1.90) and model 3 (OR = 1.42, 95% CI: 1.01-2.00) data were consistent with model 1 data. Additionally, the number of Circs components was positively associated with CD in all three models. Subgroup analyses revealed an association between CD and Circs in participants who had high blood pressure (OR = 2.46, 95% CI: 1.48-4.11, p < 0.001). Conclusion: In this cross-sectional study, we found that Circs is positively associated with the risk of CD in US adults, especially in those with high blood pressure. This association may provide new management strategies for CD.

Characteristics of non-carbapenemase producing carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital in China.

INTRODUCTION: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a substantial severe global public health burden. Non-carbapenemase-producing CRKP (non-CP-CRKP) is increasingly recognized as the source of severe infections. METHODOLOGY: We analyzed the genotypic, and phenotypic profiles of non-CP-CRKP strains with the whole-genome sequences isolated between 2017 and 2019 and the clinical characterization of non-CP-CRKP infection. RESULTS: A total of 91 CRKP strains were collected, of which 5 (5.49%) strains were non-CP-CRKP. Four strains were from male patients; three strains were isolated from the bile of patients who underwent biliary interventional surgery and four had a history of antibiotic exposure. Three strains were sequence type (ST)11, one was ST1, and one was ST5523. The non-CP-CRKP strains were insusceptible to ertapenem. Three strains were susceptible to amikacin. All the strains were susceptible to imipenem, meropenem, tigecycline, ceftazidime/avibatam and polymyxin B. The ß-lactamases of non-CP-CRKP predominantly included blaCTX-M, blaSHV, and blaTEM subtypes. Two site mutations in ompK36 (p.A217S and p.N218H) and four in ompK37 (p.I70M, p.I128M, p.N230G, and m233_None234insQ) were detected accounting for carbapenem resistance. Plasmids IncFI and IncFII were found in most strains. Genes encoding aerobactin, yersiniabactin and allantoin utilization were not detected in several isolates, and all non-CP-CRKP strains did not carry rmpA gene. CONCLUSIONS: Non-CP-CRKP infected patients had a history of previous antibiotic exposure or invasive procedures. Non-CP-CRKP strains were insusceptible to ertapenem. The mechanism of resistance includes ß-lactamases production and the site mutations in ompK36 and ompK37. Several virulence genes were not detected in non-CP-CRKP.

Prognostic model of immune-related genes for patients with hepatocellular carcinoma.

Background: Immune-related genes (IRGs) are closely connected to the occurrence and development of tumors. Their influence on the prognosis of patients with HCC, however, remains unclear. Methods: From the TCGA database, we integrated 365 liver cancer tissues and 50 normal tissues to identify differential immune genes related to prognosis. Multivariate COX analysis was used to establish a new prognostic index on account of IRGs, whereby risk score = (Expression level of HSPA4*0.022) + (Expression level of PSMD14*0.042) + (Expression level of RBP2*0.019) + (Expression level of MAPT*0.197) + (Expression level of TRAF3*0.146) + (Expression level of NDRG1*(0.006) + (Expression level of NRAS*0.027) + (Expression level of IL17D*0.075). Results: The risk score was clearly correlated with an unfavorable survival rate and with clinical characteristics. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1-, 3- and 5-year AUC of 0.721, 0.747 and 0.781, respectively). Conclusion: We have established a valuable prognostic risk score for HCC patients that may be a better predictor of survival than the present method. With the risk score's strong predictive value for immune cells and functions, it may provide clinical guidance for the diagnosis and prognosis of different immunophenotypes, and provide multiple therapeutic targets for the treatment of HCC patients based on subtype-specific immune molecules.

Advanced intestinal regulation improves bowel preparation quality in patients with constipation: A systematic review and network meta-analysis.

Background: Inadequate bowel preparation (IBP) has a critical influence on the colonoscopy procedure and is associated with significantly lower rates of detection of colorectal lesions. Constipation is an important risk factor of IBP, and some studies have attempted to address the bowel cleansing for constipated patients. However, there is still lack of consensus to guide the clinical work of bowel preparation (BP) for patients with constipation. Therefore, we aimed to perform a network meta-analysis to compare the overall efficacy of various regimens for BP in constipated patients. Methods: We performed a comprehensive search of PubMed, MEDLINE, EMBASE, Cochrane, and Web of science to identify randomized controlled trials (RCTs) of bowel preparation regimens in constipated patients, update to January 2021. Two investigators independently evaluated articles and extracted data. The odds ratio (OR) with a 95% confidence interval (CI) was used to combine dichotomous data of the primary outcome which was defined as adequate bowel preparation (ABP). Rank probability was used to exhibit the outcome of the network meta-analysis. Results: Eleven studies that included 1891 constipated patients were identified as suitable for inclusion. The proportion of ABP was associated with the administration of intensive regimen (OR 2.19, 95% CI 1.16-4.17, p = .02, I2 = 84%). Moreover, an intensive regimen had a significant efficacy and light heterogeneity when the same basic laxative program was used (OR 4.06, 95% CI 3.04-5.43, p < .0001, I2 = 0%). In the network meta-analysis, the protocol of a normal regimen + A (normal regimen plus advanced intestinal regulation) had a significant effect for bowel preparation compared with a normal regimen + IR (normal regimen plus irritating laxative regimen) (OR 5.21, 95% CI 1.18-24.55), H PEG (4L- polyethylene glycol) (OR 8.70, 95% CI 1.75-52.56), and normal regimen (NR) (OR 7.37, 95% CI 2.33-26.39). In the remaining protocols, no significant difference was observed in any comparison. No significant severe adverse events (AEs) associated with bowel preparation were reported in included studies. Conclusion: Intensive regimens could improve bowel cleansing quality for patients with constipation, and advanced intestinal regulation regimens may be superior to others.

Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke-Induced Oxidative Stress.

Stroke is a leading cause of death and disability in humans. The excessive production of reactive oxygen species (ROS) is an important contributor to oxidative stress and secondary brain damage after stroke. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme complex consisting of membrane subunits and cytoplasmic subunits, regulates neuronal maturation and cerebrovascular homeostasis. However, NADPH oxidase overproduction contributes to neurotoxicity and cerebrovascular disease. NADPH oxidase has been implicated as the principal source of ROS in the brain, and numerous studies have shown that the knockout of NADPH exerts a protective effect in the model of ischemic stroke. In this review, we summarize the mechanism of activation of the NADPH oxidase family members, the pathophysiological effects of NADPH oxidase isoforms in ischemic stroke, and the studies of NADPH oxidase inhibitors to explore potential clinical applications.

Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma.

Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.

AAIT: A novel prognostic model for HIV-negative patients with cryptococcal meningoencephalitis New Scoring Model for Non-HIV Patients with CM.

Cryptococcal meningitis (CM) is a common opportunistic infection in HIV-negative patients, with mortality rates as high as those in the HIV-negative population. This requires accurate initial clinical decision-making, warranting the development of a prognostic score. Two groups of patients were investigated separately to develop a novel prognostic model (AAIT) for HIV-negative patients with CM. A retrospective analysis of 201 HIV-negative patients with CM was conducted to develop the CM prognostic score. In addition, the CM cohort (n = 21) was recruited longitudinally to verify the new prognostic score. Meanwhile, the association between the prognostic score and 1-year mortality of CM was expounded. AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a novel prognostic score based on age, albumin level, combined bacterial infection, and total triiodothyronine (TT3) level, which were significantly higher in nonsurvivors than in survivors (0.68 [-0.70 to 1.55] vs - 1.72 [-3.75 to -0.73], P < .00). Regarding the AAIT-predicted 1-year mortality, the area under the receiver operating characteristic curve (AUROC) value was 0.857, whereas it was 0.965 for the validation cohort. In the induction period, different treatment options did not seem to significantly improve the 1-year survival rate. AAIT is a straightforward and clear prognostic score that can add value to predict the outcomes in HIV-negative patients with CM. In addition, controlling infection and increasing the albumin and TT3 levels may help improve clinical outcomes in HIV-negative patients with CM. LAY ABSTRACT: AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a straightforward and clear prognostic score that can add value to predict the outcomes HIV-negative patients with CM.