BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.
Humans ; Inflammatory Bowel Diseases/therapy*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective To investigate whether the PI3K/AKT/Cdkn1a/GPX4 signaling axis participates in the pathogenesis of radiation-induced heart disease (RIHD) through the ferroptosis pathway. Methods An RIHD mouse model was established by irradiating C57BL/6J mice with 20 Gy X-rays. Transcriptomic sequencing, the FerrDb ferroptosis-related gene set, and weighted gene co-expression network analysis were used to identify hub genes associated with ferroptosis in RIHD. KEGG enrichment analysis was employed to determine key signaling pathways. An AC16 cardiomyocyte model of RIHD was constructed, and the optimal modeling conditions were determined using CCK-8 assays and flow cytometry. Reverse transcription-quantitative PCR and Western blotting were applied to validate the expression changes of key genes and pathways in cardiomyocytes. Results Compared with the control group, myocardial tissues from irradiated mice exhibited typical RIHD pathological alterations, including structural disorganization and degeneration. Bioinformatics analysis identified Cdkn1a and Ddit4 as potential hub genes, with the PI3K/AKT pathway as the key signaling pathway. The optimal conditions for establishing the RIHD cell model were determined to be 10 Gy irradiation and 48 hours of incubation. Cellular experiments confirmed that, compared with the control group (0 Gy), irradiated cardiomyocytes (10 Gy) showed significantly elevated CDKN1A expression (P < 0.01), inhibited phosphorylation of the PI3K/AKT signaling pathway (P < 0.05), downregulated GPX4 expression (P < 0.05), and induction of ferroptosis. Conclusion This study preliminarily clarifies the potential role of the PI3K/AKT/Cdkn1a/GPX4 signaling axis in regulating ferroptosis in RIHD cardiomyocytes, providing new therapeutic targets and strategies for the prevention and treatment of RIHD.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To explore the natural course of ulcerative proctitis (UP) and the risk factors associated with disease extent progression.Methods:A retrospective cohort study was conducted, including UP patients who had undergoing prospective regisration in the Department of Gastroenterology, Xijing Hospital of Digestive Diseases, Air Force Medical University between January 2000 and May 2023. All patients were ≥ 18 years old at the time of diagnosis and followed up for more than one year. The disease extent in patients at diagnosis and during follow-up was assessed according to the Montreal classification. The clinical data were compared between the progression group and the non-progression group. The cumulative proportions of disease extent progression were analyzed with the Kaplan-Meier method, and the risk factors associated with disease extent progression were analyzed with the Cox proportional hazards regression model.Results:A total of 184 UP patients were included, with a median follow-up time of 4.8 (2.8, 8.5) years. Among them, 96 were male (52.2%) and 88 were female (47.8%), with a median age at diagnosis of 39.1 (28.8, 49.7) years. At the time of diagnosis, 95 (51.6%) patients had moderate endoscopic manifestations and 64 (34.8%) had severe endoscopic manifestations, while only 25 (13.6%) patients had mild lesions. 116 patients (63.0%) experienced disease extent progression in a median time of 4.2 (1.8, 9.0) years. The cumulative proportions of disease extent progression in 1, 3, 5, and 10 years were 13.0%, 39.0%、56.7% and 78.3%, respectively. Cox regression analysis identified the use of 5-aminosalicylic acid as a protective factor against disease extent progression ( HR = 0.55, 95% CI: 0.31 ~ 0.96, P = 0.035). During follow-up, only one patient (0.5%) underwent surgery. Five patients (2.7%) were diagnosed with dysplasia, and all of these patients had experienced disease extent progression before the development of dysplasia. Conclusions:Patients with UP had a high proportion of moderate-to-severe active endoscopic findings at diagnosis, and nearly two-thirds of patients experienced disease progression during follow-up, but the rates of colectomy and neoplasia were relatively low. 5-ASA was a protective factor against disease extent progression.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To explore the natural course of ulcerative proctitis (UP) and the risk factors associated with disease extent progression.Methods:A retrospective cohort study was conducted, including UP patients who had undergoing prospective regisration in the Department of Gastroenterology, Xijing Hospital of Digestive Diseases, Air Force Medical University between January 2000 and May 2023. All patients were ≥ 18 years old at the time of diagnosis and followed up for more than one year. The disease extent in patients at diagnosis and during follow-up was assessed according to the Montreal classification. The clinical data were compared between the progression group and the non-progression group. The cumulative proportions of disease extent progression were analyzed with the Kaplan-Meier method, and the risk factors associated with disease extent progression were analyzed with the Cox proportional hazards regression model.Results:A total of 184 UP patients were included, with a median follow-up time of 4.8 (2.8, 8.5) years. Among them, 96 were male (52.2%) and 88 were female (47.8%), with a median age at diagnosis of 39.1 (28.8, 49.7) years. At the time of diagnosis, 95 (51.6%) patients had moderate endoscopic manifestations and 64 (34.8%) had severe endoscopic manifestations, while only 25 (13.6%) patients had mild lesions. 116 patients (63.0%) experienced disease extent progression in a median time of 4.2 (1.8, 9.0) years. The cumulative proportions of disease extent progression in 1, 3, 5, and 10 years were 13.0%, 39.0%、56.7% and 78.3%, respectively. Cox regression analysis identified the use of 5-aminosalicylic acid as a protective factor against disease extent progression ( HR = 0.55, 95% CI: 0.31 ~ 0.96, P = 0.035). During follow-up, only one patient (0.5%) underwent surgery. Five patients (2.7%) were diagnosed with dysplasia, and all of these patients had experienced disease extent progression before the development of dysplasia. Conclusions:Patients with UP had a high proportion of moderate-to-severe active endoscopic findings at diagnosis, and nearly two-thirds of patients experienced disease progression during follow-up, but the rates of colectomy and neoplasia were relatively low. 5-ASA was a protective factor against disease extent progression.

Inflammatory bowel disease (IBD) is a chronic, relapsing immune-mediated disease. Patients with IBD are at significantly increased risk of anxiety and depression, with possible mechanisms including genetic susceptibility, brain-gut axis and dysbiosis. This review summarizes the latest research progress on the epidemiology, risk factors, mechanisms and treatment of anxiety and depression in IBD patients.