A role for YAP/FOXM1/Nrf2 axis in oxidative stress and apoptosis of cataract induced by UVB irradiation.

This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.

Systematic evaluation of the diagnostic approach of inflammatory bowel disease guidelines.

OBJECTIVE: To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions. METHODS: Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated. RESULTS: Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria. CONCLUSION: The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome.

A Bayesian network meta-analysis on comparisons of intraocular lens power calculation methods for paediatric cataract eyes.

The study aimed to compare and rank the accuracy of formulas for calculating intraocular lens (IOL) power in paediatric eyes in a systematic way. A literature search was conducted in Pubmed, Web of Science, Cochrane Library, and EMBASE by December 2021. Combined with traditional and network meta-analysis, we analysed the percentages of paediatric eyes with prediction error (PE) within ±0.50 dioptres (D) and ±1.00 D as the outcome measurements among different formulas. Subgroup analyses stratified by age were also undertaken. Thirteen studies with 1781 eyes comparing 8 calculation formulas were included. For the traditional meta-analysis results, Sanders-Retzlaff-Kraff theoretical (SRK/T) (risk ratios (RR), 1.15; 95% confidence intervals (CI), 1.03-1.30) performed significantly better than the SRKII formula for the percentage of eyes with PE within ±0.50 D. In addition, SRK/T (RR, 1.10; 95% CI, 1.02-1.18) and Holladay 1(RR, 1.15; 95% CI, 1.01-1.30) both performed significantly better than the SRKII formula for the percentage of eyes with PE within ±1.00 D. Considering the ranking based on the surface under the cumulative ranking curve (SUCRA) by Bayesian method, the top four formulas were Barrett Universal II (UII), Haigis, Holladay 1, and SRK/T on the percentage of PE within ±0.50 D, whereas the top four formulas were Barrett UII, Holladay 1, SRK/T, and Hoffer Q formulas on the percentage of PE within ±1.00D. Concerning both outcome measurements of rank probabilities, the top three Barrett UII, SRK/T, and Holladay 1 formulas were considered to provide more accuracy for IOL power calculation in paediatric cataract eyes, and Barrett UII tends to perform better in older children.

Systematic appraisal of guidelines for the diagnosis of pancreatic cancer.

This review aimed at assessing current guidelines' methodological quality systematically for pancreatic cancer's diagnosis and to reveal the heterogeneity of the recommendations among the evaluated guidelines. A systematic search was conducted to find the latest guidelines for pancreatic cancer's diagnosis. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to assess the qualified guidelines' feature. We extracted the main recommendations for the diagnosis of pancreatic cancer from the guidelines and performed a heterogeneity evaluation. The highest-level evidence that supported these recommendations was further extracted and analysed. Nine guidelines for the diagnosis of pancreatic cancer were included in this study. Four of the guidelines had an overall score of more than 60% and thus are recommended for clinical use. Further analysis of the heterogeneity of the main recommendations for the diagnosis of pancreatic cancer in the guidelines revealed that the recommendations vary greatly among the different guidelines. The main reasons for the great differences include the neglect of symptoms and signs, great differences in the items involved in recommendations for the diagnosis of pancreatic cancer, inconsistent recommendations for some indicators (carbohydrate antigen 19-9 and ERCP), the unreasonable citation of evidence, and the failure of some recommendations to provide evidence supporting the recommendations. For most recommendations, there was a low level of evidence and a dearth of high-quality study evidence. Recommendations for pancreatic cancer diagnosis have been significantly inconsistent over the past five years. The quality of the guidelines for diagnosing pancreatic cancer also varies. The improvement by the guideline creators of the factors that contribute to the differences mentioned above will be a shortcut to update the guidelines for the diagnosis of pancreatic cancer.