Alternative splicing generates cancer‐specific transcripts and is now recognized as a hallmark of cancer. However, the critical oncogenic spliceosome‐related proteins involved in triple‐negative breast cancer (TNBC) remain elusive. Here, we explored the expression pattern of spliceosome‐related proteins in TNBC, non‐TNBC, and normal breast tissues from The Cancer Genome Atlas breast cancer (TCGA‐BRCA) cohort, revealing higher expression of nearly half of spliceosome‐related proteins in TNBC than their counterparts. Among these TNBC‐specific spliceosome‐related proteins, the expression of SNRPB2 was associated with poor prognosis in patients with TNBC. In TNBC cells, the knockdown of SNRPB2 strongly suppressed cell proliferation and invasion and induced cell cycle arrest. Mechanistically, transcriptome data showed that SNRPB2 knockdown inactivated E2F1 signaling, which regulated the cell cycle. We further validated the downregulation of several cell cycle genes in SNRPB2 knockdown cells. Moreover, the analysis showed that SNRPB2 knockdown triggered the alteration of many alternative splicing events, most of which were skipping of exon. In TNBC cells, it was found that SNRPB2 knockdown led to the skipping of exon 6 in MDM4 pre‐mRNA, generating MDM4‐S transcript and downregulating MDM4 protein expression. More importantly, downregulation of MDM4 decreased retinoblastoma 1 (Rb1) protein expression, which is a target of MDM4 and a regulator of E2F1 signaling. In summary, the current study revealed an SNRPB2/MDM4/Rb axis in promoting the progression of TNBC, providing novel insights and novel targets for combating TNBC.

Upper gastrointestinal bleeding (UGIB) is a prevalent and severe complication of cirrhosis, often resulting from esophagogastric variceal bleeding (EVB). This condition poses significant life-threatening risks. Once bleeding occurs, the risk of recurrent episodes substantially increases, further compromising liver function and worsening patient outcomes. This study aims to identify risk factors for UGIB in cirrhotic patients using clinical examination data and to develop a non-invasive predictive model to improve diagnostic precision and efficiency. Based on the inclusion and exclusion criteria, the study included 140 cirrhotic patients hospitalized at the First Affiliated Hospital of Nanjing Medical University between June 2022 and May 2023, who experienced UGIB within six months after discharge. These patients were compared with 151 cirrhotic patients hospitalized at the same hospital during the same period, who were discharged within six months without experiencing UGIB. General characteristics of the patients during hospitalisation, laboratory parameters on admission, and liver and spleen stiffness were retrospectively collected, and a retrospective case-control study was conducted. All patients were randomly assigned to the training and validation sets in a ratio of 7:3. Independent factors associated with UGIB were identified by univariate analysis, multivariate logistic regression analysis, and stepwise regression analysis, on the basis of which a predictive model was developed. The model’s performance was assessed via receiver operating characteristic (ROC) curve and decision curve analysis (DCA) and was compared with established prognostic models, including the Child-Pugh and MELD scores. The study analyzed 291 patients with cirrhosis, of whom 208 were allocated to the training set and 83 to the validation set. Independent predictors were identified, and predictive models were constructed using multivariate logistic regression analysis, and stepwise regression analysis in the training set, followed by validation in the validation set. The stepwise regression analysis identified ascites, spleen stiffness, albumin, fibrinogen, total cholesterol, and total bilirubin as independent predictors of UGIB (P < 0.05). These variables were incorporated into the predictive model. The area under the curve (AUC) for UGIB prediction was 0.956 in the training set and 0.909 in the validation set, demonstrating strong predictive performance. Furthermore, comparative analysis using ROC and DCA demonstrated that the developed model outperformed established scoring systems, such as the Child-Pugh score and the MELD score. Ascites, spleen stiffness, albumin, fibrinogen, total cholesterol and total bilirubin as independent predictors of UGIB in cirrhotic patients.

Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects. Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed. DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation. Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.