Objective To investigate the value of serum thymidine kinase 1(TK1),hypoxia-inducible fac-tor-1α(HIF-1α)and squamous cell carcinoma antigen(SCC)in the diagnosis and prognosis of esophageal cancer.Methods A total of 105 patients with esophageal cancer treated in the Qinhuai Medical Zone of East-ern Theater General Hospital from February 2019 to October 2021 were selected as the study group,and 80 healthy subjects were selected as the control group during the same period.The serum levels of TK1,HIF-1αand SCC were compared between study group,control group and patients with different pathological charac-teristics.Patients with esophageal cancer were followed up for 3 years,and the overall survival(OS)and pro-gression-free survival(PFS)were recorded.Receiver operating characteristic curve was used to analyze the di-agnostic efficiency of serum TK1,HIF-1α and SCC combined detection for esophageal cancer,Pearson correla-tion analysis was used to analyze the correlation between the serum indicators,and Kaplan-Meier survival a-nalysis was used to analyze the OS and PFS of patients with different serum levels of TK1,HIF-1α and SCC.Multivariate COX regression was performed to analyze prognostic factors.Results Compared with the control group,the serum TK1,HIF-1α and SCC levels in the study group increased(P＜0.05).The area under the curve(AUC)of serum TK1,HIF-1α,SCC alone and combined for diagnosis of esophageal cancer were 0.893,0.744,0.841,0.922,respectively,and their combined diagnoses of esophageal cancer had the largest AUC.Se-rum TK1,HIF-1α and SCC in patients with different TNM stages and differentiation stages were significantly different(P＜0.05).Serum TK1,HIF-1α and SCC in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05).Serum TK1 was positively correlated with HIF-1α and SCC levels in patients with esophageal cancer(P＜0.05).The survival functions of OS and PFS in TK1,HIF-1αand SCC low expression group were better than those in high expression group(P＜0.05).Multivariate COX regression analysis showed that low differentiation and lymph node metastasis were independent risk factors for poor prognosis in esophageal cancer patients(P＜0.05).Conclusion Serum levels of TK1,HIF-1α and SCC are increased in patients with esophageal cancer,the combined diagnosis of the three is effective.The high expression of TK1 and HIF-1αand SCC will shorten OS and PFS.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

This study aims to investigate the isolate and identify of infectious bronchitis virus(IBV)in chickens,and study its genetic variation and pathogenicity.In 2023,two strains named CK/CH/HN/SQ202301 and CK/CH/HN/SQ202302 were obtained from suspected infectious bronchitis(IB)infected materials collected in a region of Henan Province,China.Further analysis showed that the two isolates belong to the G Ⅰ-13 and GⅥ genotypes,respectively.The cleavage sites of S protein were all RRSRR.The prediction of glycosylation sites showed that the two isolates had 18 and 12 N-glycosylation sites respectively,but no O-glycosylation site.Recombinant analysis shows that C2023-1 was a recombinant strain.Pathogenicity was assessed by infecting 1-day-old SPF chicks with the two isolates,and the results showed that C2023-1 strain infection could cause clini-cal symptoms such as depression and head shaking,as well as death in chicks,with a mortality rate of 37.5％.There were no clinical symptoms or deaths after infection with C2023-2 strain.Viral load test results showed that both isolates continued to detoxify until the 10th day,and had strong rep-lication capacity in the kidney,trachea and bursa of Fabricius.The results indicate significant differences in the genetic characteristics and pathogenicity of the two isolates due to their different genotypes.This study not only provides new epidemiological data on IB,which contributes to a bet-ter understanding of IBV's epidemiological features and control challenges,but also adds valuable bioinformatics resources for IBV by analyzing its variation mechanisms and biological information.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective To evaluate the effectiveness of vaccination on the onset of varicella and clinical symptoms of varicella based on the survey data of varicella outbreaks in schools.Methods Six schools with chickenpox outbreaks in Shaanxi Province were selected as the sites,and students in the classes or dormitories where the cases were located were chosen as the research subjects.A 1∶2 matching case control was used to conduct a questionnaire survey to analyze the relationship between the history of varicella vaccine immunization and the incidence of chickenpox so as to evaluate the effectiveness of varicella vaccine.Results The total prevalence of the six varicella outbreaks involved in this study was 1.39％.The proportion of chickenpox vaccinations was 44.53％,of which 15.78％ were vaccinations with two doses.The overall effectiveness of varicella vaccine was 63.52％ (95％ CI:40.690％-77.560％),and the effectiveness of one and two doses was 58.72％ and 72.90％,respectively.The effectiveness of varicella vaccine against moderate to high fever and moderate to severe rash was 82.77％ and 76.27％,respectively.The risk of chickenpox in people with vaccination intervals of 6 to 8 years and ≥ 9 years was 13.05 times and 3.93 times higher than that of those vaccinated before the age of 3 years,respectively.Conclusion Varicella vaccine has a good effectiveness on high-exposure people,and the effectiveness of two doses is better than that of one dose.Varicella vaccination can lessen the clinical symptoms of chickenpox.It is recommended to further strengthen the publicities of varicella vaccination and increase the number of children to complete two doses of varicella vaccination before entering nurseries,so as to actively and effectively control varicella outbreaks.

Objective To investigate the efficacy and safety of self-help inflatable balloon in the treatment of refractory benign upper digestive tract stricture.Methods From November 2022 to February 2024,10 patients with refractory benign upper digestive tract stricture underwent self-help inflatable balloon were retrospectively analyzed.Preoperative treatment,intraoperative and postoperative complications,dysphagia score before and after surgery,wearing time of external self-help inflatable balloon,and the clinical efficacy were evaluated.Results All the 10 patients received self-help inflatable balloon treatment.No complications such as bleeding and perforation occurred in all patients during the wearing of the balloon.The placement time of the balloon was 60～180 d,and the average wearing time was 104.9 d.Before surgery,nine cases had a stricture segment length less than 2 cm,and one case had a stricture segment length of 6 cm.The dysphagia score before surgery was(3.60±0.52),and the dysphagia score after removal of the self-help inflatable balloon was(0.60±0.52),and there was statistical significance in preoperative and postoperative comparison(P＜0.05).The dysphagia score 3 months after removal of the external self-help inflatable balloon was(0.70±0.48),there was no significant difference in dysphagia score between the day after surgery and 3 months after surgery(P＞0.05).The diameter of the stricture before and after operation was(5.09±2.02)mm and(10.35±0.73)mm respectively,and the difference was statistically significant(P＜0.05).Sore throat,wing of nose pain and balloon displacement were the most common adverse events,with 30.0％(3/10),50.0％(5/10)and 70.0％(7/10),respectively.Conclusion It is safe,effective and feasible to treat refractory benign upper digestive tract stricture with self-help inflatable balloon in vitro.It is worthy for clinical application.

Objective To analyze the clinical characteristics and risk factors of children with B-cell acute lymphoblastic leukemia(B-ALL)who developed acute pancreatitis(AP)after treatment with pegaspargase(PEG-ASP).Methods A retrospective analysis was conducted on the general data,clinical data,blood routine data,albumin concentration,and cumulative dose of PEG-ASP of 272 children with ALL complicated with AP who received PEG-ASP treatment in the hospital from January 2021 to February 2023.The correlations between gender,age,risk stratification,cumulative dose of pegaspargase,blood routine indicators,albumin concentration and the progression of pancreatitis were analyzed.Results Among the 272 children,the incidence of AP was 8.5%(23/272).There was no statistically significant correlation between AP and gender,age,body mass index(BMI),risk stratification,cumulative dose of pegaspargase,hemoglobin concentration,platelet count and monocyte count(P>0.05),but there was a significant correlation with white blood cell count,neutrophil count,lymphocyte count,neutrophil/lymphocyte ratio,platelet/lymphocyte ratio and albumin concentration(P<0.05).Logistic regression analysis further showed that white blood cell count,neutrophil count,lymphocyte count and albumin concentration were related to the occurrence of PEG-ASP-related AP(P<0.05).ROC analysis found that white blood cell count,lymphocyte count and albumin concentration could predict the occurrence of PEG-ASP-related AP.Conclusions White blood cell count,neutrophil count,lymphocyte count and albumin concentration are risk factors for PEG-ASP-related AP in children with B-ALL.Especially,abnormal white blood cell count,lymphocyte count and albumin concentration in blood routine examination can help identify high-risk children with B-ALL complicated with PEG-ASP-related AP at an early stage.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.