Adoptive cell transfer (ACT) shows significant efficacy against hema-tological malignancies but is limited in solid tumors due to poor homing, immunosuppre-ssion, and potential toxicity. Biomaterials spanning from nano- to macroscales-including nanoparticles, microspheres/micropatches, and hydrogels-offer unique advantages for ex vivo cell engineering, in vivo delivery, and modulation of the tumor microenvironment. Specifically, nanoparticles enable gene delivery, artificial antigen-presenting cell engi-neering, and immune microenvironment remodeling. Microspheres/micropatches improve immune cell expansion, targeted activation, and localized retention. Hydrogels enhance ACT via in situ genetic engineering, 3D culture support, and cytokine co-delivery. This review summarizes advances in biomaterial-enhanced ACT, highlighting their potential to improve delivery efficiency, amplify antitumor responses, and reduce toxicity. These insights may accelerate the clinical translation of ACT for solid tumors.
Humans ; Neoplasms/therapy* ; Biocompatible Materials/chemistry* ; Immunotherapy, Adoptive/methods* ; Nanoparticles ; Hydrogels ; Adoptive Transfer/methods* ; Animals

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

Objective:To explore the value of cardiac magnetic resonance imaging (CMR) derived left ventricular late gadolinium enhancement (LV LGE) for the primary prevention of malignant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.Methods:This was a single-center retrospective study. Consecutive ARVC patients who underwent CMR at Fuwai Hospital between January 2016 and September 2020, with no history of malignant ventricular arrhythmias at diagnosis, were enrolled. Clinical data and CMR characteristics were collected. The primary endpoint was defined as new-onset malignant ventricular arrhythmias related events, including sustained ventricular tachycardia, ventricular fibrillation/flutter, sudden cardiac death, cardiac arrest, and appropriate implantable cardioverter-defibrillator discharge. Follow-up via telephone interviews and medical records was conducted to confirm endpoint occurrences, and patients were categorized into event-free and event groups based on endpoint status. Univariable and multivariable Cox regression analysis were performed to identify independent risk factors for malignant ventricular arrhythmias in ARVC patients. Subgroup analyses were conducted based on the ARVC 5-year risk score (cutoff: 25%) and the median value of LV LGE percentage (cutoff: 13%). Kaplan-Meier curves were plotted, and log-rank tests were used to compare the difference in the incidence of primary endpoint events between subgroups. Receiver operating characteristic curves and likelihood ratio test were used to evaluate the incremental prognostic value of LV LGE percentage beyond the ARVC 5-year risk score.Results:A total of 172 ARVC patients were enrolled, aged (39.0±16.6) years, including 73 females (42.4%). During a follow-up of 53.1 (25.4, 76.9) months, 51 patients (29.7%) experienced malignant ventricular arrhythmias related events, including 3 cases of sudden cardiac death, 1 cardiac arrest, 33 sustained ventricular tachycardia and 14 appropriate implantable cardioverter-defibrillator discharges. Multivariable Cox regression analysis indicated that the ARVC 5-year risk score ( HR=1.028, 95% CI 1.015-1.041, P<0.001) and LV LGE percentage ( HR=1.059, 95% CI 1.032-1.087, P<0.001) were independent risk factors of the primary endpoint events. Kaplan-Meier analysis using composite stratification (ARVC 5-year risk score cutoff: 25%; LV LGE percentage cutoff: 13%) demonstrated that patients with both high risk scores (≥25%) and extensive LV LGE (≥13%) had the highest risk of primary endpoint events. Notably, among patients with ARVC 5-year risk scores <25%, those with LV LGE≥13% had a higher incidence of primary endpoint events than those without (log-rank P=0.037). The composite prediction model combining the 5-year risk score and left ventricular LGE percentage demonstrated significantly improved predictive performance (area under the curve ( AUC)=0.82, 95% CI 0.75-0.90; likelihood ratio test all P<0.001) compared to single-variable models (left ventricular LGE percentage alone: AUC=0.71, 95% CI 0.63-0.82, P=0.01; 5-year risk score alone: AUC=0.71, 95% CI 0.62-0.81, P=0.02). Conclusion:LV LGE percentage independently predict new-onset malignant ventricular arrhythmias in ARVC patients and provided incremental prognostic value based on the existing ARVC 5-year risk score.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

Objective:To explore the value of cardiac magnetic resonance imaging (CMR) derived left ventricular late gadolinium enhancement (LV LGE) for the primary prevention of malignant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.Methods:This was a single-center retrospective study. Consecutive ARVC patients who underwent CMR at Fuwai Hospital between January 2016 and September 2020, with no history of malignant ventricular arrhythmias at diagnosis, were enrolled. Clinical data and CMR characteristics were collected. The primary endpoint was defined as new-onset malignant ventricular arrhythmias related events, including sustained ventricular tachycardia, ventricular fibrillation/flutter, sudden cardiac death, cardiac arrest, and appropriate implantable cardioverter-defibrillator discharge. Follow-up via telephone interviews and medical records was conducted to confirm endpoint occurrences, and patients were categorized into event-free and event groups based on endpoint status. Univariable and multivariable Cox regression analysis were performed to identify independent risk factors for malignant ventricular arrhythmias in ARVC patients. Subgroup analyses were conducted based on the ARVC 5-year risk score (cutoff: 25%) and the median value of LV LGE percentage (cutoff: 13%). Kaplan-Meier curves were plotted, and log-rank tests were used to compare the difference in the incidence of primary endpoint events between subgroups. Receiver operating characteristic curves and likelihood ratio test were used to evaluate the incremental prognostic value of LV LGE percentage beyond the ARVC 5-year risk score.Results:A total of 172 ARVC patients were enrolled, aged (39.0±16.6) years, including 73 females (42.4%). During a follow-up of 53.1 (25.4, 76.9) months, 51 patients (29.7%) experienced malignant ventricular arrhythmias related events, including 3 cases of sudden cardiac death, 1 cardiac arrest, 33 sustained ventricular tachycardia and 14 appropriate implantable cardioverter-defibrillator discharges. Multivariable Cox regression analysis indicated that the ARVC 5-year risk score ( HR=1.028, 95% CI 1.015-1.041, P<0.001) and LV LGE percentage ( HR=1.059, 95% CI 1.032-1.087, P<0.001) were independent risk factors of the primary endpoint events. Kaplan-Meier analysis using composite stratification (ARVC 5-year risk score cutoff: 25%; LV LGE percentage cutoff: 13%) demonstrated that patients with both high risk scores (≥25%) and extensive LV LGE (≥13%) had the highest risk of primary endpoint events. Notably, among patients with ARVC 5-year risk scores <25%, those with LV LGE≥13% had a higher incidence of primary endpoint events than those without (log-rank P=0.037). The composite prediction model combining the 5-year risk score and left ventricular LGE percentage demonstrated significantly improved predictive performance (area under the curve ( AUC)=0.82, 95% CI 0.75-0.90; likelihood ratio test all P<0.001) compared to single-variable models (left ventricular LGE percentage alone: AUC=0.71, 95% CI 0.63-0.82, P=0.01; 5-year risk score alone: AUC=0.71, 95% CI 0.62-0.81, P=0.02). Conclusion:LV LGE percentage independently predict new-onset malignant ventricular arrhythmias in ARVC patients and provided incremental prognostic value based on the existing ARVC 5-year risk score.

Objective To investigate the active ingredients of Zizyphi Spinosae Semen(ZSS)in relieving benzodiazepine(BDZ)dependence and its molecular mechanism based on the integrated Traditional Chinese Medicine and chemical drugs idea of"enhancing effect and reducing toxicity"via the approach of network pharmacology and the technique of molecular dynamics simulation.Methods First,literature search was undertaken to find the main components of ZSS.Then,the major effective constituents of ZSS in relieving BDZ dependence and its target of action were explored on the basis of network pharmacology and molecular docking.Finally,the relationship between core components of ZSS and key proteins was further verified through the technique of molecular dynamics simulation.Results After literature search,a total of 24 chemical components in ZSS were found to act on 731 targets.Through establishing the network of"ingredients-targets-pathways",topology analysis was performed to obtain nine core components such as linoleic acid,palmitic acid,oleic acid,tetradecanoic acid,spinosin,oleanolic acid and jujuboside A,as well as five key targets including AR,PTGS2,PPARG,RXRA and CYP19A1.Bioinformation enrichment analysis was made to obtain critical pathways such as calcium signaling pathway,cAMP signaling pathway,IL-17 signaling pathway and TNF signaling pathway.The results of molecular docking revealed that there was a good combination between core components of ZSS and key targets,and it was mainly dominated by hydrogen bonding.Furthermore,the molecular dynamics simulation experiments indicated that the combinations between jujuboside A and RXRA,oleanolic acid and RXRA,spinosin and PPARG were stable,and these three active ingredients played an important role in improving BDZ dependence.Conclusion The active components in ZSS may exert multi-target and multi-pathway intervention effects on BDZ dependence by means of processes such as immunoregulation,anti-anxiety,and anti-insomnia.

Objective To study the application effect of quality control circle(QCC)in reducing the dissatisfaction rate of physical examination clients in health management center.Methods To establish QCC,selected the health check-up popula-tion in our hospital in September-2019 and March-2020,through the questionnaire investigation and analysis,compare the dis-satisfaction of the clients before and after the quality control circle.Results After carrying out QCC activities,the dissatisfaction of physical examination clients was significantly lower than that before QCC,and the difference was statistically significant(P＜0.05).Conclusion The activities of QCC in the health management center can effectively improve the quality of the physical examination work and reduce the dissatisfaction of the customers in the physical examination.It is of great significance to the health management.

Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.