Acute necrotizing pancreatitis (ANP) is often complicated by multiple organ failure. The small intestine is frequently damaged during ANP. Capillary leakage in multiple organs during ANP is one of the most important causes of multiple organ dysfunction. Damage to the capillary endothelial barrier and impaired water transportation could lead to capillary leakage in ANP. Sprague–Dawley (SD) rats were randomized into a control group, the ANP group, the culture media-treated group, or the bone marrow-derived mesenchymal stem cell (BMSC)-treated group (30 rats in each group). Ten rats in each group were sacrificed at 6, 12, and 24 h after induction of experimental models. Serum, ascites, pancreatic, and small intestinal samples were collected. The levels of serum and ascites albumin and amylases were measured, pancreatic histology was assessed, and the connection changes between vessel endothelial cells were evaluated using scanning electron microscopy (SEM). Capillary leakage in small intestinal tissue was observed visually by tracking fluorescein isothiocyanate (FITC)-albumin, and was measured by the Evans blue extravasation method. The location and expression of aquaporin 1 (AQP1) in the small intestine was analyzed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot. The outcomes showed that the level of serum and ascites amylase is elevated. Conversely, the level of serum albumin is decreased while ascites albumin is elevated. There is damage to pancreatic tissue, and the small intestinal capillary endothelial barrier was aggravated. Furthermore, the expression of AQP1 was reduced significantly after induced ANP. Following treatment with MSCs, the elevation of amylase and the decrease of serum albumin were inhibited, the damage to pancreatic tissue and the level of small intestinal capillary leakage was alleviated, and the downregulation of AQP1 was reversed. In conclusion, MSC therapy could alleviate small intestinal injury in rats with ANP, the mechanism of which might be related to reduction of damage to the small intestinal capillary endothelial barrier, and increased expression of AQP1 in the small intestine.

In multiple malignant tumors, circular RNAs (circRNAs) are believed to play a crucial role. Our prior results demonstrated that circ_ZNF778_006 was significantly increased in esophageal squamous cell carcinoma (ESCC) tissues, but the roles of circ_ZNF778_006 in ESCC is still not clear. The expression of circ_ZNF778_006 was compared in different pathological grades of ESCC. And the expression levels of circ_ZNF778_006, miR-18b-5p, HIF-1α were analyzed by qRT-PCR and Western blot, respectively. Plasmid transfection techniques were applied to prepare ESCC cells with silenced or overexpressed genes (CircZNF778_006, miR-18b-5p). The CCK8 kit was used to determine cell proliferation, and the Transwell assay was used to measure the migration and invasion. The effects of circ_ZNF778_006 on tumor growth was investigated in vivo. Furthermore, luciferase reporter gene assay and RNA-binding protein immunoprecipitation (RIP) were performed to verify the targeting relationship between miR-18b-5p and circZNF778_006, miR-18b-5p and HIF-1α. The expression of circ_ZNF778_006 was positively correlated with pathological grade in ESCC. Circ_ZNF778_006 significantly inhibited sensitivity to 5-fluorouracil & cisplatin. It could promote the proliferation, invasion, migration in ESCC cells and accelerated tumor growth in vivo. Furthermore, circ_ZNF778_006 could upregulate the expression of HIF-1α via sponing miR-18b-5p. Circ_ZNF778_006 promoted ESCC progression by upregulating HIF-1α expression via sponging miR-18b-5p.

Clear cell renal cell carcinoma (ccRCC) remains a major clinical challenge, with high rates of recurrence and limited long-term survival despite surgical resection and VEGF-targeted therapy. Immune checkpoint inhibitors (ICIs)—targeting PD-1, PD-L1, and CTLA-4—have revolutionized first-line systemic treatment, particularly in combination with VEGF tyrosine kinase inhibitors or as dual ICI regimens. However, primary and acquired resistance, immune-related adverse events (irAEs), and heterogeneous treatment responses limit the durability of benefit in many patients. This review aims to address a central question: how can immunotherapy for ccRCC evolve from incremental survival extension to durable, potentially curative control? We highlight emerging strategies—including next-generation checkpoint inhibitors (LAG-3, TIM-3, TIGIT), bispecific T cell engagers, cytokine-based agents, CAR-T and TCR-T therapies, and cancer vaccines—designed to enhance and sustain anti-tumor immunity. In parallel, we examine the role of multi-omic and spatial biomarkers, such as PBRM1 mutations, interferon-γ signatures, single-cell spatial atlases, and gut microbiome profiles, in refining patient selection and predicting therapeutic outcomes. This review uniquely integrates mechanistic insights with translational advances, providing a forward-looking synthesis of precision immunotherapy in ccRCC. We also emphasize rational combination strategies, biomarker-guided personalization, and irAE management as key priorities to overcome resistance and improve long-term outcomes.

Background: Dysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated.Methods: Initially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays.Results: The downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET.Conclusion: Collectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p–SOCS4 axis may provide great potential in establishing ESCC therapy.

Purpose: Pulmonary metastasis is relatively rare among esophageal cancer patients, and there is a limited body of research in this regard. This study used clinical and pathological indicators from monitoring, epidemiological, and Surveillance, Epidemiology, and End Results (SEER) databases to look at the risk factors for patients who develop pulmonary metastasis. This study aims to explore the risk factors for lung metastasis in esophageal cancer patients and their impact on prognosis, and to construct a nomogram model for predicting the survival period of patients with lung metastasis. Methods: We obtained data on esophageal cancer patients from the Surveillance, SEER database between 2010 and 2015. Patients with esophageal cancer lung metastasis were divided into a training group and a testing group. Univariate and multivariate analyses were performed on the training set to identify independent risk factors for esophageal cancer lung metastasis, and a nomogram model was constructed to predict overall survival (OS). The model’s discriminatory ability and calibration were evaluated using the C-index, area under the receiver operating characteristic (ROC) curve (AUC), and calibration curve. Results: A total of 10,035 esophageal cancer patients were included in this study, with 590 diagnosed with lung metastasis. Single-factor and multi-factor logistic regression analyses revealed several risk factors associated with esophageal cancer lung metastasis, including male gender, higher tumor grades (Grade II and Grade III), advanced T stage, and the presence of bone, brain, and liver metastases. Patients diagnosed with esophageal cancer who have pulmonary metastases have a median overall survival of six months. For patients with esophageal cancer with lung metastasis, significant prognostic factors identified by Cox regression analysis included tumor grade (grade II and III), T2 lymph node metastasis, T3 lymph node metastasis, and the presence of bone metastasis. The constructed nomogram was validated by ROC analysis and calibration curves, demonstrating good predictive accuracy and discriminatory power. Conclusions: There are certain differences in risk and prognostic factors between patients with esophageal cancer and lung metastasis. ROC curves and calibration curves validated that the dynamic nomogram has certain predictive performance.