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Background: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases. [ABSTRACT FROM AUTHOR]

Objective: To determine whether risk stratification can optimize the benefits of flexible sigmoidoscopy (FSG) screening., Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted from 1993 to 2001 in the United States. A colorectal cancer (CRC) risk stratification tool was developed in the control arm (n = 64,207) from the PLCO cohort and validated in the UK Biobank (n = 270,726). PLCO participants (n = 130,021) were classified into low-, medium-, and high-risk groups. Cumulative incidence and mortality were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between screening and CRC incidence and mortality., Results: The CRC risk stratification tool was based on age, gender, body mass index, smoking status, family history of CRC, diabetes, regular use of aspirin, and CRC screening history. Compared with the control arm, FSG screening was significantly associated with a reduction in mortality in both the medium-risk (HR = 0.76, 95% CI = 0.63-0.92) and high-risk groups (0.58, 0.46-0.73), but not in the low-risk group (0.85, 0.61-1.19). FSG screening also reduced distal CRC incidence and mortality in the medium-risk and high-risk groups. Furthermore, it was associated with a reduction in incidence (0.74, 0.59-0.92) and mortality (0.59, 0.40-0.87) of proximal colon cancer in the high-risk group., Conclusions: FSG screening yielded more benefits for the high-risk group than for the low-risk and medium-risk groups, supporting the development of a risk-stratified CRC screening strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Single-nucleotide polymorphism of CLPTM1L-rs401681(C > T) at the 5p15.33 locus is significantly associated with cancer risk as reported in genome-wide association studies, but the reported studies for non-melanoma skin cancer (NMSC) are inconclusive. To assess the association between rs401681[C] allele and NMSC risk, we performed this meta-analysis with four case-control studies involving 5,469 cases and 39,715 controls. Our meta-analysis showed that rs401681[C] allele was associated with NMSC susceptibility in the overall subjects (C vs. T, OR 1.13, 95 % CI 1.07-1.20). In the stratified analysis, the rs401681[C] allele confers susceptibility in Icelanders (C vs. T, OR 1.15, 95 % CI 1.06-1.26) and non-Icelanders (C vs. T, OR 1.13, 95 % CI 1.03-1.24). In the subtype analysis, we found that rs401681[C] allele was a risk factor for BCC, but not SCC in the overall subjects.

Objective: Epinephrine has a place in the treatment of pediatric cardiopulmonary arrest but has been controversy concerning its optimal dose. This meta-analysis aimed to seek for evidences of the effectiveness of different doses of epinephrine in children with cardiac arrest and to evaluate the effectiveness of high-dose versus standard-dose epinephrine in children with cardiac arrest., Method: Published papers on randomized controlled trials (RCTs) and prospective clinical controlled trials (CCTs) were electronically searched from MEDLINE (1966 to September 2006), EMBASE (1974 to June 2006), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006), CBM (1998 to 2006) and CNKI (1994 to 2006). We also had searched the related references and manual retrieval 10 professional academic journals about epinephrine treatment of pediatric cardiopulmonary arrest (1998 to 2006). The search strategy was made according to the collaborative review group search strategy. At first, we found 546 articles. Second, we excluded 474 of them through reading the title, abstract, excluding non-randomized, non-controlled trials and non-clinical studies. Finally, we identified 4 papers through searching for original articles and telephone contact with some of the authors after excluding 68 papers. Then we performed the meta-analysis by RevMan 4.2.7. For homogenous dichotomous data (P > or = 0.1, I(2) < or = 50%) we calculated fixed effects model, relative risk (RR), 95% confidence intervals (CI), For heterogeneity Dichotomous data (P < 0.1, I(2)>50%) we calculated random effects model, relative risk (RR) and 95% confidence intervals (CI)., Result: Four trials involving 360 cases were included. The results of meta-analysis indicated that there were no statistical difference in recovery of spontaneous circulation [RR = 1.28, 95% CI (0.93, 1.77)]. Perondi, Patterson and Cheng xiuyong's study compared the rate of survival at 24 hours and showed statistical heterogeneity (P = 0.01, I(2) = 0.77). The random effects model indicated that there were no significant difference [RR = 1.40, 95% CI (0.43, 4.55)]. The sensitivity analysis showed that after deleting Perondi's group there were no statistical heterogeneity. Fixed effects model indicated that there were significant difference [RR = 2.50, 95% CI (1.52, 4.11)]. T When the rates of survival to hospital discharge were compared among the 4 studies, there was statistical heterogeneity (P = 0.07, I(2) = 0.58), the random effects model indicated that there were no statistical difference [RR = 1.78, 95% CI (0.42, 7.50)], There were no heterogeneity after Cheng Xiu-yong group was deleted., Conclusion: Higher doses of epinephrine in children with cardiopulmonary arrest may not increase the rate of recovery of spontaneous circulation, the rate of survival at 24 hours, the rate of survival to hospital discharge and worsen the neurological outcomes. Adverse reactions is difficult to monitor and evaluate because of the current restrictions on medical technology.