Int J Med Sci
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Background: BMS-1166, a PD-1/PD-L1 inhibitor, inhibits the binding of PD-L1 to PD-1, restores T cell function, and enhances tumor immune response. However, mutations in the tumor suppressor or impaired cellular signaling pathways may also lead to cellular transformation. In this study, the SW480 and SW480R cell lines were used as the model to elucidate the treatment with BMS-1166, BEZ235, and their combination. ⋯ Conclusions: PD-1 binds to PD-L1 and activates the PI3K/mTOR and MAPK pathways, which might be the molecular mechanism of acquired resistance of CRC to BMS-1166. The combination of the two drugs inhibited the phosphorylation of PI3K, Akt, and Erk in the PI3K/mTOR and MAPK pathway, i.e., BEZ235 enhanced the BMS-1166 treatment effect by blocking the PI3K/mTOR pathway and interfering with the crosstalk of the MAPK pathway. Therefore, these findings provide a theoretical basis for BMS-1166 combined with BEZ235 in the trial treatment of colorectal cancer.
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Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. ⋯ Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD.
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Observational Study
The Association between Percentage of Mean Arterial Pressure and Long-Term Mortality in Acute Myocardial Infarction Patients: An Observational Cohort Study.
Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. ⋯ However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.
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Objective: This study aims to propose a personalized cancer prediction model based on the metabolic-inflammatory-nutritional score (MINS) for predicting lymph node metastasis (LNM) in endometrial cancer (EC) and validated prediction of survival probability in patients with a family history of Lynch syndrome-associated cancers (LSAC). Methods: A total of 676 patients diagnosed with EC were enrolled in this study. We calculated the optimal cutoff value using restricted cubic splines (RCS) analysis or the mean value. ⋯ Additionally, a nomogram was demonstrated effective predictive performance with a C-index of 0.778 (95% CI: 0.725-0.832). Conclusion: Preoperative MINS has been determined to be associated with the risk of LNM in EC patients. Utilizing MINS as a basis, the development of a prognostic nomogram holds promise as an effective tool for risk stratification in clinical settings among EC patients with a family history of LSAC.
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Objectives: In this study, we aimed to assess the maximal oxygen uptake (VO2max) of young, healthy, non-athletic Saudi men using maximum graded exercise with instant breath-by-breath analysis and to compare this value to the predicted VO2max by international formulae. Methods: In this cross-sectional study, 88 young non-athletic normal-weight Saudi subjects were recruited from Eastern Province of Saudi Arabia with mean age (21.3 ± 1.5 years), weight: (64.7 ± 7.5 kg), height: (172.3 ± 6.1 cm) and body mass index: (21.8 ± 2.1). All subjects were interviewed and examined for eligibility, after which they performed maximum graded exercise testing on a treadmill to obtain VO2max. ⋯ This value was lower than Western values, which might be due to low physical activity or racial differences. Most international formulae overestimate the VO2max in this population, except for the Hansen equation. Therefore, Hansen's predicted VO2max might be the best available reference value for the diagnosis and prognosis of young Saudi individuals undergoing maximum exercise testing.