The ratio of high aspartate aminotransferase to alanine aminotransferase: an independent risk factor associated with poor prognosis in IgA nephropathy.

OBJECTIVE: To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). METHODS: Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. RESULTS: After a mean follow-up of 29 months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. CONCLUSION: AAR is an independent prognostic factor in patients with IgAN.

Analysis of predictive factors of thrombosis in autogenous arteriovenous fistula.

PURPOSE: To investigate the predictors of early diagnosis of thrombus of autogenous arteriovenous fistula (aAVF). METHODS: The included patients were divided into the thrombus group with aAVF failure or thrombosis and the control group with good internal fistula function. The general data of the patients, including age, sex, diabetes mellitus, were collected. Platelets (PLT), platelet crit (P-LCR), platelet distribution width (PDW), mean platelet volume (MPV), homocysteine (HCY), and other biochemical data were collected. The predictors of thrombus of aAVF were obtained by the t test and logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was used to compare the area under the ROC curve (AUC) between the combined predictors and the original indicators. The optimal critical value was determined when the Youden index reached its maximum value, and the sensitivity, specificity, accuracy, diagnostic index, and so on were calculated. Finally, prediction was performed by substituting each value in individually. RESULTS: PLT, PDW, P-LCR, MPV, and HCY showed significant differences between two groups (p < 0.05). Logistic regression analysis showed that, for PLT (OR = 1.014, 95% CI 1.006-1.022, p = 0.01), PDW (OR = 1.295, 95% CI 1.009-1.661, p = 0.042), P-LCR (OR = 1.230, 95% CI 1.089-1.389, p = 0.001), MPV (OR = 1.696, 95% CI 1.101-2.613, p = 0.017), and HCY (OR = 1.332, 95% CI 1.182-1.502, p = 0.01), the difference was significant; PLT, PDW, P-LCR, MPV, and HCY were positively correlated with thrombogenesis (p < 0.05). By logistic regression, a group of the five predictors of PLT, PDW, P-LCR, MPV, and HCY was obtained, and the combined predictors were 0.014*PLT + 0.258*PDW + 0.207*P-LCR + 0.528*MPV + 0.287*HCY. The area under the curve of the combined predictor was 0.933, the sensitivity was 92.4%, the specificity was 81.2%, the maximum diagnostic index was 0.736, the diagnostic cutoff point was 21.790, and the accuracy rate was 87%. CONCLUSION: PLT, PDW, P-LCR, MPV, and HCY are predictors of thrombus of aAVF. They can better predict thrombus of aAVF, and the combination of these five indicators is better than a single indicator.

AKT1 phosphorylates RBM17 to promote Sox2 transcription by modulating alternative splicing of FOXM1 to enhance cancer stem cell properties in colorectal cancer cells.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic-induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17-mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1-RBM17-FOXM1-Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.

Features of the Influence of a DNA Sequence on Its Adjacent Sequence.

To explore the features of the influence of a DNA sequence (here called sequence A) on its adjacent sequence (here called sequence B), we linked some DNA repeated sequences to the 5'-end of the T7 promoter in the plasmid pET-42a (+) or the 5'- and/or 3'-end(s) of the EcoRI site in some DNA fragments using PCR and other molecular cloning methods. As a result, we found that the efficiency of the T7 promoter and EcoRI could be impacted by some flanking sequences, indicating that sequence B could be impacted by sequence A. The features of such influence include the following: (i) sequence A can directly impact sequence B without changing/modifying the base composition of sequence B or destroying the inherent connection between sequence B and its function-related sequences; (ii) such influence does not need the participation of trans-acting factors or products of sequence A (if any); (iii) such an influence might be undetectable when the activities of trans-acting factors of sequence B are normal but might become detectable when those are lower than the normal one; (iv) such an influence might be enhancive, inhibitory, or unobvious; (v) the influence of sequence A linked to the 5'-end of sequence B might be the same as or opposite to that of sequence A linked to the 3'-end; and (vi) the influences of sequence A linked to different ends of sequence B could enhance or partially offset each other when sequence A is linked to both 5'- and 3'-ends of sequence B. These findings might give us a further understanding of the interaction of two adjacent DNA sequences.

Effects of psychoeducation for depression on help-seeking willingness: biological attribution versus destigmatization.

Existing literature shows that the level of biological attribution and stigma of depression influences willingness to seek help. However, no study has used experimental methods to explore the question whether increasing biological attribution and decreasing blameworthy attitude towards depression will enhance willingness to seek help. In so doing, 299 college students were randomly assigned to biological, destigmatization, combined, and control groups. The measures included the Biological Attribution Scale, Psychological Blame Scale, and Help-Seeking Willingness Scale. The data were analyzed by a 2 x 2 ancova (with or without biological attribution education x with or without destigmatization education) on willingness to seek professional help which was assessed 2 weeks later, with adjusting for help-seeking willingness at baseline. Results showed that biological education had a significant main effect to elevate help-seeking willingness, but destigmatization education did not. In addition, no interaction effect existed between the two independent variables. The authors suggested that biological education makes people legitimize depression as a disease entity, so that it would be a practical approach to increase people's motivation to solve their emotional afflictions, especially in societies that emphasize emotional constraints. In contrast, although destigmatization information reduces people's negative appraisals to the depressed individuals, it does not go a step further to increase people's motivation to seek professional help. Further studies are needed to clarify the mechanisms of educational effects.