This cohort study aimed to investigate the association between steroid injections for shoulder diseases and the increased incidence of cuff tendon tears. The Kaohsiung Veterans General Hospital clinical database was used in this study. Patients were enrolled using the corresponding diagnostic codes for shoulder diseases. Patients who received steroid injections were included in the case group, and those without steroid injections were included in the control group. The outcome measure was the occurrence of cuff tendon tears during the study period. Adjusted hazard ratios for outcomes were calculated using Cox regression analysis adjusted for sex, age, and comorbidities. Of the 1025 patients with shoulder disease, 205 were in the case group and 820 were in the control group. The incidence of cuff tendon tears was 9.8% in patients who received steroid injections (p < 0.001). The adjusted hazard ratios for steroid injections, smoking, and chronic liver disease were 7.44 (p < 0.001), 2.40 (p = 0.046), 3.25 (p = 0.007), respectively. Steroid injections on the shoulder were associated with a raised risk of cuff tendon tears by 7.44 times compared to non-injection. The incidence of cuff tendon tears increased by 3.25 times with concurrent chronic liver disease and by 2.4 times with smoking.

Sialylation of glycoproteins is modified by distinct sialyltransferases such as ST3Gal, ST6Gal, ST6GalNAc, or ST8SIA with α2,3-, α2,6-, or α2,8-linkages. Alteration of these sialyltransferases causing aberrant sialylation is associated with the progression of colon cancer. However, among the ST8- sialyltransferases, the role of ST8SIA6 in colon cancer remains poorly understood. In this study, we explored the involvement of ST8SIA6 in colon cancer using multiple gene databases. The relationship between ST8SIA6 expression and tumor stages/grades was investigated by UALCAN analysis, and Kaplan–Meier Plotter analysis was used to analyze the expression of ST8SIA6 on the survival outcome of colon cancer patients. Moreover, the biological functions of ST8SIA6 in colon cancer were explored using LinkedOmics and cancer cell metabolism gene DB. Finally, TIMER and TISMO analyses were used to delineate ST8SIA6 levels in tumor immunity and immunotherapy responses, respectively. ST8SIA6 downregulation was associated with an advanced stage and poorly differentiated grade; however, ST8SIA6 expression did not affect the survival outcomes in patients with colon cancer. Gene ontology analysis suggested that ST8SIA6 participates in cell surface adhesion, angiogenesis, and membrane vesicle trafficking. In addition, ST8SIA6 levels affected immunocyte infiltration and immunotherapy responses in colon cancer. Collectively, these results suggest that ST8SIA6 may serve as a novel therapeutic target towards personalized medicine for colon cancer.

Individuals of Asian descent are at higher risk for developing hyperuricemia and gout as compared to Western populations. Urate-lowering therapy (ULT) is an effective treatment for hyperuricemia and gout. It was reported that febuxostat, one of the ULTs, raises the risk of atrial fibrillation (AF) in elderly populations. Nevertheless, this association has not been properly investigated in Asian populations. We aimed to investigate the development of AF after ULT with different drugs in an Asian population. We conducted a retrospective cohort study using the clinical database at Kaohsiung Veterans General Hospital. Patients newly diagnosed with gout between 1 January 2013 and 31 December 2020 and with a documented baseline serum uric acid (sUA) level but no prior diagnosis of AF were identified. Patients were divided into three groups—allopurinol, benzbromarone, and febuxostat users. During the follow-up period, the risks of incident AF following the initiation of ULT with different drugs were assessed. Development of incident AF was noted in 43 (6%) of the 713 eligible patients during the follow-up period (mean, 49.4 ± 26.6 months). Febuxostat-treated patients had a higher prevalence of certain comorbidities (diabetes mellitus, heart failure, and chronic kidney disease) and higher CHA2DS2-VASc scores. Compared with allopurinol, neither febuxostat nor benzbromarone was associated with increased adjusted hazard ratios (HR) for incident AF (HR: 1.20, 95% confidence interval [CI]: 0.43–3.34; HR: 0.68, 95% CI: 0.22–2.08). There was no difference in the risk of incident AF among Asian patients with gout who received febuxostat, allopurinol, or benzbromarone. Further studies are needed to evaluate long-term cardiovascular outcomes in patients receiving different ULT drugs.

Clear cell renal cell carcinoma (ccRCC) is the most common RCC subtype with a high mortality. It has been reported that delta-like 1 homologue (DLK1) participates in the tumor microenvironmental remodeling of ccRCC, but the relationship between delta-like 2 homologue (DLK2, a DLK1 homologue) and ccRCC is still unclear. Thus, this study aims to investigate the role of DLK2 in the biological function and disease prognosis of ccRCC using bioinformatics analysis. The TNMplot database showed that DLK2 was upregulated in ccRCC tissues. From the UALCAN analysis, the overexpression of DLK2 was associated with advanced stage and high grade in ccRCC. Moreover, the Kaplan-Meier plotter (KM Plotter) database showed that DLK2 upregulation was associated with poor survival outcome in ccRCC. By the LinkedOmics analysis, DLK2 signaling may participated in the modulation of ccRCC extracellular matrix (ECM), cell metabolism, ribosome biogenesis, TGF-β signaling and Notch pathway. Besides, Tumor Immune Estimation Resource (TIMER) analysis showed that the macrophage and CD8⁺ T cell infiltrations were associated with good prognosis in ccRCC patients. Finally, DLK2 overexpression was associated with the reduced macrophage recruitments and the M1–M2 polarization of macrophage in ccRCC tissues. Together, DLK2 may acts as a novel biomarker, even therapeutic target in ccRCC. However, this study lacks experimental validation, and further studies are required to support this viewpoint.

Background and purpose: Alcoholic cardiomyopathy (ACM) is a serious complication of chronic and acute alcohol abuse that can progress to heart failure (HF). Currently, no curative drug exists for ACM, and heart transplantation remains the only definitive option. Although mineralocorticoid receptor (MR) antagonists (MRAs) are a cornerstone of HF management, their role in ethanol cardiotoxicity remains poorly defined. Because ethanol elevates aldosterone levels, targeting the aldosterone/MR axis may represent a promising therapeutic strategy. This study investigated the effects of finerenone, a next-generation non-steroidal MRA, in both in vitro and in vivo models of acute alcoholic myocardial injury. Methods: H9c2 cardiomyocytes were exposed to ethanol with or without finerenone, and cell viability, apoptosis, mitochondrial dynamics, and proinflammatory signaling were assessed to evaluate cytoprotective effects. In vivo , a murine acute alcoholic myocardial injury model was generated by three days of ethanol exposure with concurrent finerenone administration. Circulating myocardial injury marker CK-MB was measured, and myocardial tissue was analyzed for MR/aldosterone levels, apoptosis, inflammation, macrophage infiltration, and mitochondrial fission/fusion dynamics. Results: Finerenone attenuated ethanol-induced MR upregulation, apoptosis, mitochondrial fragmentation, and pro-inflammatory signaling in H9c2 cardiomyocytes. In mice, finerenone further reduced the ethanol-induced increase in serum CK-MB and attenuated ethanol-induced myocardial cell death and damage. Moreover, ethanol-induced myocardial inflammation, oxidative stress, and mitochondrial dysfunction were further reduced in this mouse model of ethanol cardiotoxicity following finerenone administration. Together, the non-steroidal MRA finerenone may attenuate acute ethanol-induced cardiotoxicity by regulating inflammatory pathways, oxidative stress, and mitochondrial function. Conclusions and implications: Overall, these findings support the conclusion that the next-generation MRA finerenone attenuates acute ethanol-induced myocardial cell death, inflammation, oxidative stress, and mitochondrial dysfunction in vitro and in vivo . Finerenone may act as a novel protective agent against acute alcoholic myocardial injury in the future, but further clinical evidence is required to support this preclinical finding.