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.

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

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.

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 clinical characteristics, diagnosis, treatment, and prognosis of postpartum ovarian vein thrombosis (OVT) combined with inferior vena cava thrombosis (IVCT).Methods:A retrospective analysis was conducted on the clinical data of a postpartum OVT case combined with IVCT treated in the Department of Obstetrics of the Affiliated Women's and Children's Hospital, School of Medicine, University of Electronic Science and Technology of China (Chengdu Women and Children's Central Hospital). Chinese literature was searched in CNKI, Wanfang Database, Yiigle, and VIP Database using the keywords "ovarian vein thrombosis," "inferior vena cava thrombosis," and "pregnancy." English literature was searched using the same keywords in PubMed, Embase, and UpToDate databases. The search period was from January 1995 to January 2024. Exclusion criteria were: (1) OVT not combined with IVCT; (2) incomplete clinical data. These cases' clinical characteristics, diagnosis, treatment, and prognosis were analyzed using a descriptive statistical analysis.Results:(1) Case report: The patient, a 31-year-old woman, underwent a full-term cesarean section due to breech presentation and premature rupture of membranes. Three days postoperatively, she developed abdominal pain and right-sided back pain without fever. Ultrasound indicated bilateral renal pelvis separation, and CT angiography revealed right OVT combined with IVCT. She was transferred to the Vascular Surgery Department of West China Hospital, Sichuan University, where she received anticoagulant therapy with nadroparin for 10 days and was discharged in stable condition. She continued oral rivaroxaban anticoagulation therapy after discharge. At a three-month follow-up, the patient reported no discomfort. (2) Literature review: Twenty articles (18 in English and two in Chinese) involving 21 patients were identified. Including the case from our hospital, there were 22 cases in total. The average age of the 22 patients was (29.7±2.5) years, ranging from 16 to 39 years. The onset of the condition postpartum was (6.2±1.9) days, ranging from 1 to 30 days. Sixteen cases (72.7%) were cesarean deliveries, and six cases (27.3%) were vaginal deliveries (including one case with forceps assistance). Fourteen cases (63.6%) had right-sided OVT combined with IVCT, and eight cases (36.4%) had pulmonary embolism and other deep vein thromboses. Symptoms among the 22 patients included fever (14 cases, 63.6%), lower abdominal pain (16 cases, 72.7%), back pain and chest pain (three cases each, 13.6%), dyspnea (two cases, 9.1%), cough, and syncope (one case in each, 4.5%). Five patients were initially diagnosed via ultrasound, and 22 were confirmed through CT scans. Nine patients reported D-dimer levels at the onset of the disease, averaging (2.74±1.01) mg/L. Treatment methods included anticoagulation (22 cases, 100.0%), antibiotics (14 cases, 63.6%), thrombectomy (three cases, 13.6%), placement of inferior vena cava filters (seven cases, 31.8%), and thrombolysis (three cases, 13.6%). The mean time of anticoagulant therapy for the 22 patients was (2.4±0.5) months, ranging from two weeks to six months. One patient developed a rectus sheath hematoma during anticoagulation therapy, which required a one-day cessation of anticoagulation. After stabilization, the therapy was resumed, and both the thrombosis and hematoma were resolved.Conclusions:For postpartum patients presenting with unexplained fever, abdominal pain, low back pain, or chest pain, the possibility of ovarian vein thrombosis should be considered. Consultation with relevant departments and imaging examinations should be conducted when necessary to ensure early detection and treatment.

Objective:To explore the factors of trial of labor after cesarean(TOLAC)and analyze the outcomes of mother and fetus.Methods:A total of 308 pregnant women who underwent TOLAC in the Department of Ob-stetrics of Chengdu Women and Children Center Hospital from January 2019 to June 2023 were selected as the study group,and 308 pregnant women who underwent direct cesarean section with scarred uterus during the same period were selected as the control group.The study group was divided into two subgroups according to the successful results:vaginal delivery success group(VBAC group)and trial delivery failure to cesarean section group(RCD group).Clinical data such as the general conditions of pregnant women at admission and the out-comes of mother and fetus were recorded,and the univariate and multivariate analysis was performed to analyze the factors influencing success of VBAC.Results:①A total of 10243 pregnant women were pregnant again after cesarean section,with a TOLAC rate of 3.01％and 254 cases in the VBAC group,with a success rate of 82.46％.The top three factors for conversion surgery were suspected fetal distress,pain and unwillingness to try labor,sus-pected uterine rupture or threatened uterine rupture.②The 24-hour blood loss,newborn body mass,hospitaliza-tion days and hospitalization cost of the study group were lower than those of the control group(P＜0.05).In the study group,the 24-hour blood loss,newborn body mass,complication rate,hospitalization days and hospitaliza-tion cost in VBAC group were all lower than those in RCD group(P＜0.05).③There was no statistically signifi-cant difference in the incidence of neonatal asphyxia,blood transfusion and complications between the study group and the control group(P＞0.05).④The univariate analysis of factors affecting the success of VBAC showed that the height and Bishop score of pregnant women in VBAC group were higher than those in RCD group.Pregnant women in VBAC group had ruptured membranes at admission,had a history of delivery or in-duced labor for more than 24 weeks,and hadnatural labor was higher than those in RCD group.The uterine height and estimated fetal weight of pregnant women in VBAC group were lower than those in RCD group(P＜0.05).There was no statistically significant difference between the VBAC group and the RCD group in induction of labor by oxytocin and balloon plus oxytocin(P＞0.05).⑤Multivariate Logistic regression analysis showed that the height of pregnant women ≥ 160 cm(OR 2.461,95％CI 1.343-6.402)and Bishop score ≥6(OR 3.420,95％CI 1.224-9.560),membranous rupture on admission(OR 10.557,95％CI 1.295-86.075),and natural labor(OR 7.083,95％CI 2.659-18.868)were independent favorable factors for the success of VBAC(P＜0.05).Conclu-sions:Vaginal delivery after cesarean section has good social and economic benefits.For pregnant women who are willing to undergo TOLAC,a comprehensive assessment should be made based on the height,Bishop score,uterine height,fetal size,etc,when admitted to the hospital to improve the probability of successful delivery.At the same time,monitoring should be strengthened during delivery and early decision should be made to reduce adverse outcomes and ensure the safety of mother and fetus.

Objective To investigate the effect of short-term blood glucose control on neurovascular coupling in pa-tients with diabetes mellitus type 2(T2DM).Methods The patients with T2DM who were admitted to Department of En-docrinology,The Second Affiliated Hospital of Hainan Medical University,from December 1,2021 to May 30,2023 were consecutively included in this study,and according to whether examination was performed before or after blood glucose control,they were divided into pre-blood sugar control T2DM group(T2DM-Pre-c group)and post-blood sugar control T2DM group(T2DM-Pro-c group).Healthy volunteers matched for age and sex were enrolled as healthy control(HC)group.Transcranial Doppler was used to monitor cerebral blood flow parameters,including mean blood flow velocity(Vm)of the middle cerebral artery during elbow flexion,and the T2DM group and the HC group were compared in terms of the changes in cerebral blood flow parameters after blood glucose control.Results A total of 52 T2DM patients and 36 healthy volunteers were enrolled in this study.Compared with the HC group,the T2DM-Pre-c group had significantly higher exercise-induced pulsatility index,resistance index,and time to peak of Vm(TTP-Vm)(all P<0.05).The T2DM-Pre-c group had a significantly lower Vm slope than the HC group(P=0.031).The T2DM-Pro-c group had a significant in-crease in Vm slope and a significant reduction in TTP-Vm after blood glucose control(P<0.05).Conclusion Impair-ment of neurovascular coupling is observed in patients with T2DM during the state of hyperglycemia,and short-term blood glucose control can improve neurovascular coupling.