Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent mucosal inflammation. Although biologics and small-molecule therapies can effectively suppress inflammation, only 13%-34% of patients achieve deep histological remission, and most experience relapse within 2-3 years. Existing biomarkers, including C-reactive protein (CRP), fecal calprotectin, and endoscopic measures, have limited ability to detect subclinical molecular abnormalities, suggesting that disease-driving factors may persist even during clinical remission. Recently, Pang et al. reported a study in Science that investigated the role of epithelial cell-death signaling using a prospective adult IBD cohort comprising 80 participants and more than 900 biopsy specimens. By integrating bulk and spatial transcriptomics, patient-derived organoids, and 24-36 months of longitudinal follow-up, the authors characterized epithelial cell-death programs associated with IBD persistence. They found that the necroptosis-associated marker pRIPK3 could be detected in the absence of overt histological inflammation and persisted during advanced therapy. IFN‑γ and TNF reshaped the transcriptional landscape of specific colonic epithelial cells, inducing an inflammatory macrophage-like program termed cluster B and triggering RIPK1-independent RIPK3 signaling. This was followed by NOS2/iNOS-mediated mitochondrial apoptosis driving colonocyte death, whereas PUMA-dependent apoptosis contributed to intestinal stem-cell loss. Higher baseline pRIPK3 levels were associated with subsequent disease activity, although their independent predictive value remains to be established. These findings suggest that persistent IBD may reflect not only residual immune inflammation but also inflammation-induced pathological epithelial states. Future therapeutic strategies may therefore need to extend beyond inflammation control toward “molecular repair”, including targeting noncanonical RIPK3 signaling, modulating iNOS/PUMA-dependent mitochondrial apoptosis, and developing relapse-risk stratification strategies based on tissue biomarkers such as pRIPK3. Such approaches may help shift the therapeutic goal from “clinical remission” toward “molecular healing”.

OBJECTIVES: To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA). METHODS: Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1. RESULTS: A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC₅₀ of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001). CONCLUSIONS High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.
Humans ; Urinary Bladder Neoplasms/genetics* ; Immunotherapy ; Prognosis ; Pyrroline Carboxylate Reductases/metabolism* ; Biomarkers, Tumor/genetics* ; delta-1-Pyrroline-5-Carboxylate Reductase ; Microsatellite Instability ; Tumor Microenvironment ; Mutation ; Computational Biology ; Molecular Docking Simulation

Health communication aims to improve public health attitudes and behaviors by propagating health information. It plays an important role in promoting public health literacy and "Healthy China Initiative". The basic theories of health communication include "7 W" and Theory of Planned Behavior. Clinicians with profound medical expertise and a wealth of clinical practice play key roles in the communication, and they hold an unparalleled advantage in health communication by delivering authoritative and trustworthy information to the public. The capacity of health communication among clinicians in the nation is determined by various factors including professional characteristics, policy support, dissemination platforms and pathways, time and effort. Meanwhile, some problems in the research on the health communication capacity of clinicians remain, such as lack of well-established motivation systems, limited dissemination pathways, and imperfect evaluation frameworks. In some regions of China, health communication performance has been considered as part of the professional title evaluation for clinical physicians. Medical institutions and universities have also initiated relevant training and practice programs. It is crucial to improve evaluation frameworks, strengthen training pathways and effectiveness assessment, promote interdisciplinary integration, and enhance the role of clinicians in health communication in the future.

Objective:To investigate the neurobiochemical metabolites of caudate nucleus and thalamus in patients with obsessive-compulsive disorder and their relationship with obsessive-compulsive symptoms.Methods:From April 2019 to January 2022 in Beijing Anding Hospital, totally 25 untreated patients with obsessive-compulsive disorder were recruited, and 20 healthy controls matched with gender, age and educational background were recruited for the study.The maps of neurobiochemical metabolites of patients and normal controls were collected by hydrogen proton magnetic resonance spectroscopy.With bilateral caudate nucleus and thalamus as brain regions of interest.The relative concentrations of N-acetylaspartic acid (NAA), glutamic acid (Glu) and γ-aminobutyric acid (GABA) were fitted by LCModel software.At the same time, the clinical symptoms of patients were evaluated with Yale-Brown obsessive-compulsive scale (Y-BOCS) and Hamilton anxiety scale (HAMA). SPSS 20.0 software was used for statistical analysis.Independent double sample t-test was used to compare the differences of different nerve biochemical metabolite concentrations between patients with obsessive-compulsive disorders and healthy controls.Pearson correlation analysis was used to explore the correlation between biochemical metabolite concentrations and clinical symptoms. Results:The Glu concentration in the left thalamus of patients with obsessive-compulsive disorder (3.97±0.41) was higher than that of the control group (3.66±0.55)( t=-2.11, P<0.05), while the NAA concentration was (4.87±0.47)lower than that of the control group (5.15±0.44)( t=2.05, P<0.05). The GABA concentrations in the right caudate nucleus (0.50±0.18) and thalamus (0.80±0.19) were lower than those in the control group ((0.63±0.23), (0.96±0.24))( t=2.08, 2.36, both P<0.05). Pearson correlation analysis showed that the Glu concentration in the left caudate nucleus of patients with obsessive-compulsive disorder was positively correlated with the total score of Y-BOCS( r=0.46, P<0.05). Spearman correlation analysis showed that Glu concentration in the right caudate nucleus was positively correlated with the total score of HAMA in patients with obsessive-compulsive disorder ( r=0.46, P<0.05). Conclusion:NAA, Glu and GABA metabolism in caudate nucleus and thalamus are abnormal in patients with obsessive-compulsive disorder, and Glu concentration is positively correlated with the severity of obsessive-compulsive and anxiety symptoms.

OBJECTIVE: To investigate the effect of exosomal FZD10 derived from non-small cell lung cancer (NSCLC) cells on angiogenesis of human umbilical venous endothelial cells (HUVECs) and explore the possible mechanism. METHODS: We analyzed the expression of FZD10 in two NSCLC cell lines (95D and H1299 cells), normal human bronchial epithelial cells (BEAS-2B cells) and their exosomes isolated by ultracentrifugation. Cultured HUVECs were treated with the exosomes derived from NSCLC cells or NSCLC cells transfected with FZD10-siRNA, and the changes in tube formation ability of the cells were analyzed using an in vitro angiogenesis assay. ELISA was performed to determine the concentration of VEGFA and Ang-1 in the conditioned media of HUVECs, and RT-qPCR was used to analyze the mRNA levels of VEGFA and Ang-1 in the HUVECs. The effects of exosomal FZD10 on the activation of PI3K, Erk1/2 and YAP/TAZ signaling pathways were evaluated using Western blotting. RESULTS: Compared with BEAS-2B cells and their exosomes, 95D and H1299 cells and their exosomes all expressed high levels of FZD10 (P < 0.01). The exosomes derived from 95D and H1299 cells significantly enhanced tube formation ability and increased the expressions of VEGFA and Ang-1 protein and mRNA in HUVECs (P < 0.01), but FZD10 knockdown in 95D and H1299 cells obviously inhibited these effects of the exosomes. Exosomal FZD10 knockdown suppressed the activation of PI3K and Erk1/2 signaling pathways, but had no obvious effect on the activation of YAP/TAZ signaling pathway. CONCLUSION Exosomal FZD10 derived from NSCLC cells promotes HUVEC angiogenesis in vitro, the mechanism of which may involve the activation of PI3K and Erk1/2 signaling pathways.
Carcinoma, Non-Small-Cell Lung/metabolism* ; Cell Proliferation ; Culture Media, Conditioned ; Exosomes ; Frizzled Receptors/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; MicroRNAs/genetics* ; Neovascularization, Pathologic/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

Objective : To explore the role and its clinical significance of P300 in biphasic differentiation and epithelial mesenchymal transition ( EMT) process in synovial sarcoma (SS) by detecting the expression of histone acetyltransferase P300 and EMT related molecules. Methods : 40 cases of SS paraffin embedded tissue samples were collected , and the SYT⁃SSX fusion gene subtype was detected by RT⁃PCR. Immunohistochemistry was used to detect the expression of P300 and EMT⁃related molecules. : Results Conclusion P300 may be involved in the biphasic differentiation and the EMT process of SS , suggesting that P300 plays a certain role in SS invasion and migration.

Objective To explore the value of ultrasound elastography in the non-invasive monitoring of liver elasticity of stable recipients at different stages after liver transplantation. Methods Clinical data of 73 stable recipients after liver transplantation were collected. According to the time after liver transplantation, all patients were divided into the early group (n=25) and medium-to-long group (n=48). In addition, 38 healthy subjects were assigned into the control group. The ultrasound indexes and liver function indexes were statistically compared among each group. The ultrasound elastography indexes of liver and spleen were analyzed, and their correlation with liver function indexes was analyzed. Results Compared with the control group, the ultrasound indexes, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were significantly increased in the early group (all P < 0.05), and the ultrasound indexes in the medium-to-long group were significantly increased, whereas the GGT level was significantly decreased (all P < 0.05). Compared with the early group, the right oblique diameter of liver, ALT, GGT and ALP levels were significantly decreased in the medium-to-long group (all P < 0.05). Compared with the control group, the sound touch elastography (STE) and sound touch quantify (STQ) values of liver and STE value of spleen in the early group and medium-to-long group were significantly increased (all P < 0.05). Compared with the early group, the ultrasound elastography indexes of liver and spleen in the medium-to-long group were remarkably decreased (all P < 0.05). The ultrasound elastography indexes of liver were weakly correlated with the ALT, aspartate aminotransferase (AST) and GGT levels, significantly correlated with ALP level. The STE value of spleen was weakly correlated with the ALP level. The STE value of liver was significantly correlated with the STQ value of liver. The STE and STQ values of liver were weakly correlated with the STE value of spleen. Conclusions The characteristics of liver elasticity in stable recipients after liver transplantation are various among different stages. Persistent monitoring of liver elasticity may provide a novelnon-invasive monitoring method during follow-up after liver transplantation.

Metabolic disorders, such as glucose and lipid, are likely to occur after renal transplantation, leading to graft dysfunction and reduced long-term survival. Trigonelline is a type of natural alkaloid with various biological activities, which can alleviate the metabolic disorders of glucose, lipid and other types, and relieve inflammatory reaction, oxidative stress and cell apoptosis of the kidney, thereby protecting the renal function. Therefore, trigonelline may be a potential drug to regulate metabolic disorders after renal transplantation. In this article, the role of trigonelline in metabolic disorders of glucose, lipid and other types, and its application prospect in renal transplantation were reviewed, aiming to provide reference for alleviating metabolic disorders after renal transplantation and improving the long-term survival of renal transplant recipients and transplanted kidneys.

Klotho gene is an anti-aging gene that is highly expressed in the kidney. Its encoding product Klotho protein can inhibit inflammation, oxidative stress injury, and apoptosis in renal tissue. It is regarded as a renal protective protein and expected to be a new target for the treatment of renal diseases. This article reviewed the biological characteristics of Klotho and the protective effect of Klotho on renal graft function.

The tumor microenvironment is closely related to the development and progression of tumors. Chitosan has become a favorable nanocarrier for its biodegradability and biocompatibility. At present，there are two kinds of targeting ways existed in the nano-delivery system，including active and passive targeting. However，the active targeting has become the mainstream of researches owing to some factors that passive targeting contributes to drug maldistribution and high therapeutic concentration. This article reviews the important components of tumor microenvironment and the active targeting of chitosan delivery systemsand summarizes the application progress on chitosan and its derivatives actively targeting multiple components in solid tumor environment as well as perspectives on some unsolved problems.