Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To investigate the clinical and pathological characteristics, prognostic factors, and treatment outcomes of bladder adenocarcinoma.Methods:The data of 177 bladder adenocarcinoma patients treated at Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2003 to December 2023, and 2 687 bladder adenocarcinoma patients from the SEER database (2000—2021) were reviewed retrospectively. The clinicopathological and prognostic characteristics were compared between the two cohorts. Patients with urachal adenocarcinoma or primary bladder adenocarcinoma were included, while metastatic bladder adenocarcinoma from other sites and urothelial carcinoma with glandular components were excluded. The Chi-square test was used for comparison of categorical data, and propensity score matching (1∶1) was applied to match baseline data between the Renji and SEER cohorts. Kaplan-Meier survival curves were generated, and log-rank tests were used for comparisons. Univariate and multivariate Cox regression analyses were performed using the survival R package, with P-values calculated via Wald tests. Results:The proportion of localized bladder adenocarcinoma was significantly higher in the Renji cohort than in the SEER cohort [61.0% (108/177) vs. 19.4% (521/2 687), P<0.001], and mucinous adenocarcinoma was more common in Renji cohort [33.3% (59/177) vs. 22.6% (607/2 687), P<0.001]. After matching for baseline factors, including SEER stage and pathological grade, survival analysis revealed that the Renji cohort patients had slightly better survival compared to the SEER cohort [median survival: 55.4 (24.1, 196.2) months vs. 39.2 (13.6, 137.4)months, P=0.033]. Multivariate Cox analysis identified SEER stage [Renji cohort: HR=3.83 (95% CI 1.62-9.07), P=0.002; SEER cohort: HR=3.67 (95% CI 3.13-4.31), P<0.001] and pathological grade [Renji cohort: HR = 2.76 (95% CI 1.54-4.95), P=0.001; SEER cohort: HR=1.46 (95% CI 1.29-1.65), P<0.001] as independent prognostic factors. In the Renji cohort, no significant differences were observed in the median progression-free survival [40.1 (19.5, 91.6) months vs. 40.9 (12.8, not reached)months, P=0.976] and overall survival [79.3 (37.1, 195.8) months vs. 53.9 (16.4, 129.5)months, P=0.374] between patients receiving adjuvant chemotherapy and those not receiving it. However, among patients with lymph node-positive bladder adenocarcinoma, adjuvant chemotherapy significantly improved both progression-free survival [40.1 (38.2, 75.4) months vs. 12.2 (3.1, 12.2)months, P=0.004] and overall survival [68.2 (46.2, 84.5)months vs. 28.1 (4.3, 28.3)months, P=0.006]. Conclusions:Bladder adenocarcinoma is rare and associated with poor prognosis. Compared to the SEER cohort, Renji cohort patients had more localized disease, with no significant differences in other features. SEER stage and pathological grade were independent prognostic factors in both cohorts. Lymph node-positive bladder adenocarcinoma patients in the Renji cohort benefited significantly from adjuvant chemotherapy.

Obesity is a common chronic metabolic disease mainly characterized by excessive accumulation of adipose tissue.Recently,the global prevalence of obesity-related metabolic diseases has increased significantly,seriously affecting the physical and mental health of patients.Adipokines are pleiotropic bioactive substances secreted by adipose tissue,which have physiological functions such as regulating energy metabolism,inflammatory response and insulin sensitivity.Abnormal hyperplasia of adipose tissue can induce chronic inflammatory responses in the body,stimulate the production or secretion disorders of adipokines,and alter glucose and lipid homeostasis,thereby leading to the occurrence and development of obesity-related metabolic diseases.However,the specific mechanism remains unclear.Exercise prescription is a planned exercise guidance program based on the results of the patient's physical fitness test to achieve the expected goal by adopting the prescribed exercise methods.In recent years,previous studies have found that exercise prescriptions can regulate adipokines,thereby preventing and treating obesity-related metabolic disorders,which may become a potential treatment for obesity-related metabolic diseases in clinical practice.This article reviews the mechanism and clinical effect of targeted regulation of adipokines by exercise prescriptions in the treatment of obesity-related metabolic disorders,in order to provide some new ideas and directions for finding new therapies for obesity-related metabolic diseases.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

Objective To compare the diagnostic value of transabdominal intestinal ultrasound (IUS) and magnetic resonance enterography (MRE) for intestinal stenosis in inflammatory bowel disease (IBD). Methods A retrospective analysis was conducted on the imaging features of 51 IBD patients who underwent both IUS and MRE at Beijing Friendship Hospital,Capital Medical University,between January 2021 and February 2025.With endoscopy as the gold standard,the diagnostic performance of the two methods was compared. Results The sensitivity (84.2% vs. 52.6%,P=0.008) and accuracy (66.7% vs. 45.1%,P=0.035) of IUS for stenosis were higher than those of MRE.In the localization of stenosis,IUS demonstrated higher sensitivity than MRE for detecting stenosis in the terminal ileum (78.6% vs. 35.7%,P=0.070) and colorectum (86.7% vs. 53.3%,P=0.060).Furthermore,IUS showed higher diagnostic accuracy than MRE for terminal ileum stenosis (70.6% vs. 29.4%,P=0.039).The intestinal wall thickness[(8.2±2.7) mm vs. (10.3±3.8) mm;t=3.20,P=0.002)] and stenosis inner diameter[(3.0±1.6) mm vs. (4.3±1.8) mm;t=2.15,P=0.035] measured by IUS were lower than those measured by MRE,with a moderate level of consistency (ICC:0.19-0.53).In addition,IUS demonstrated a higher detection rate for mesenteric fat hypertrophy (70.6% vs. 27.5%,Kappa=0.27,P=0.005),whereas MRE was more sensitive in detecting lymphadenopathy (90.2% vs. 56.9%,Kappa=0.16,P=0.080). Conclusions IUS is superior to MRE in the diagnosis and localization sensitivity for intestinal stenosis in IBD.However,the two methods showcase poor consistency in detecting and quantitating some inflammatory signs.IUS can be used as a first-line screening method for diagnosing intestinal stenosis in IBD patients,while its clinical application should be combined with specific needs to optimize diagnosis.
Humans ; Retrospective Studies ; Constriction, Pathologic/diagnostic imaging* ; Ultrasonography/methods* ; Magnetic Resonance Imaging/methods* ; Inflammatory Bowel Diseases/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Intestines/diagnostic imaging* ; Sensitivity and Specificity