Objectives:To investigate the safety and efficacy of Cuffstent in the treatment of immediate type Ia endoleak during endovascular aneurysm repair(EVAR)of abdominal aortic aneurysm.Methods:The clinical data of 24 patients with immediate type Ia endoleak during EVAR treated with Cuffstent at the Second Xiangya Hospital of Central South University from January 2019 to December 2022 were retrospectively analyzed.There were 18 males and 6 females with a mean age of(70.3±7.1)years.Results:Of the 24 patients,22 underwent conventional proximal Cuffstent implantation,and 2 underwent fenestrated Cuffstent to preserve unilateral renal artery.Emergency EVAR was performed in 7 patients.The procedure was technically successful in all patients.Immediate disappearance of type Ia endoleak was achieved in 23 patients,whereas 1 patient exhibited mild persistent type Ia endoleak,which was managed conservatively with watchful follow-up.All the 24 patients finished an average of(39.0±15.1)months follow-up,and all patients were alive during the follow-up period.Two patients received aortic reintervention,and one patient received thoracic aortic stent graft implantation due to thoracic aortic penetrating ulcer,and one patient received abdominal aortic aneurysm resection and iliac artery stent implantation due to type II endoleak and iliac artery rupture,respectively.There were no other aorta-related complications and reintervention.Conclusions:Proximal addition of Cuffstent for the management of immediate type Ia endoleak during EVAR is safe and effective.

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To construct an in vitro co-culture model of gastric cancer organoids and cancer-associated fibroblasts(CAFs),and investigate the role of cancer-associated fibroblasts in the proliferation and chemotherapy resistance of gastric cancer organoids.Methods Tumor tissues from 12 gastric cancer patients undergoing surgical treatment in Department of General Surgery of Second Affiliated Hospital of Army Medical University from February 2023 to March 2024 were collected to construct gastric cancer organoids using 3D culture.HE staining was used to observe the morphology,and immunohistochemical assay was employed to determine the expression of cytokeratin CK7,carcinoembryonic antigen(CEA),and proliferation marker Ki-67.After CAFs derived from the same patient were cultured,observed for their morphology under a light microscope,and detected for the phenotype by flow cytometry,the cells were co-cultured with gastric cancer organoids in a 1:1 ratio.Phase-contrast microscopy was applied to observe the growth of the organoids and analyze the number,average diameter,and total area.Then,organoids cultured alone served as the control group.After the control and co-culture groups were treated with chemotherapy drugs,5-fluorouracil and oxaliplatin,for 48 h,the viability and apoptosis of organoids were assessed with CellTiter-Glo??3D assay and CellEvent? Caspase 3/7 activity,respectively.Results Gastric cancer organoids and CAFs were successfully established from 10 gastric cancer patient-derived samples.The gastric cancer organoids exhibited morphological characteristics consistent with the corresponding primary tumors,and showed positive expression of CK7,CEA,and Ki-67.CAFs displayed typical spindle-shaped morphology and exhibited the phenotypic markers CD326-,CD45-,CD31-,α-SMA+,CD73+,CD90+,and CD105+.Compared to the organoids cultured alone,the organoids co-cultured with CAFs showed more formation of organoids,in larger average diameter,and taking larger total area(P<0.05).After the treatment of 5-fluorouracil and oxaliplatin,the half-maximal inhibitory concentration(IC50)was 10.66 and 3.26 μmol/L,respectively in the control group,while was 46.23 and 91.11 μmol/L in the co-culture group.Additionally,the number of CellEvent? Caspase 3/7 positive apoptotic cells was significantly less in the co-culture group than the control group.Conclusion Compared with individually cultured gastric cancer organoids,the co-culture model of gastric cancer organoids and CAFs better simulates the pro-tumor proliferation and drug resistance effects of in vivo tumor microenvironment.

Objective To establish a mouse model of infection with the minimum lethal dose of Vibrio vulnificus(V.vulnificus)and to evaluate the protective efficacy of inactivated whole-cell(IWC)vaccine using this model.Methods A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of V.vulnificus.Bacterial colonization in the organs was detected with tissue homogenate plating,and pathological changes in the organs were observed after tissue section staining.Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension.IWC vaccine of V.vulnificus was prepared,and the mice were immunized through different routes to observe the protective efficacy of the vaccine.Results A mouse model of infection with the minimum lethal dose at 1×106 CFU of V.vulnificus was successfully established.After infection,the bacteria were mainly colonized in the liver of mice and caused severe pathological damages.Compared with the uninfected mice,the proportion of neutrophils in the liver was significantly increased in the infected mice,whereas the proportions of B cells and T cells were correspondingly decreased(P<0.05).A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of V.vulnificus in 7 d later(P<0.01),although the level of serum IgG having no significant increase.Conclusion A mouse model of lethal-dose infection with V.vulnificus is successfully established,with histopathological characteristics.The IWC vaccine of V.vulnificus rapidly mediates immune protection in this model probably independent of IgG.

Objectives:To investigate the safety and efficacy of Cuffstent in the treatment of immediate type Ia endoleak during endovascular aneurysm repair(EVAR)of abdominal aortic aneurysm.Methods:The clinical data of 24 patients with immediate type Ia endoleak during EVAR treated with Cuffstent at the Second Xiangya Hospital of Central South University from January 2019 to December 2022 were retrospectively analyzed.There were 18 males and 6 females with a mean age of(70.3±7.1)years.Results:Of the 24 patients,22 underwent conventional proximal Cuffstent implantation,and 2 underwent fenestrated Cuffstent to preserve unilateral renal artery.Emergency EVAR was performed in 7 patients.The procedure was technically successful in all patients.Immediate disappearance of type Ia endoleak was achieved in 23 patients,whereas 1 patient exhibited mild persistent type Ia endoleak,which was managed conservatively with watchful follow-up.All the 24 patients finished an average of(39.0±15.1)months follow-up,and all patients were alive during the follow-up period.Two patients received aortic reintervention,and one patient received thoracic aortic stent graft implantation due to thoracic aortic penetrating ulcer,and one patient received abdominal aortic aneurysm resection and iliac artery stent implantation due to type II endoleak and iliac artery rupture,respectively.There were no other aorta-related complications and reintervention.Conclusions:Proximal addition of Cuffstent for the management of immediate type Ia endoleak during EVAR is safe and effective.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD 19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P＜0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P＜0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P＜0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P＜0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P＜0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.

In August 2024,the European Society of Cardiology (ESC) released the 2024 edition of the Guidelines for the Management of Peripheral Arterial and Aortic Diseases. This comprehensive guideline provides detailed recommendations on the diagnosis and treatment strategies for peripheral arterial and aortic diseases (PAAD). It covers topics such as the evaluation and screening,epidemiology,treatment options,and follow-up recommendations of PAAD. With the increasing prevalence of unhealthy lifestyles and the aging population,arterial diseases have become one of the major health threats to residents in China. The detailed recommendations in this edition can be integrated with domestic guidelines to offer feasible and optimal clinical practice strategies for vascular surgeons. This article summarizes the key points and updates of the latest guideline to serve as a reference for domestic scholars.

In August 2024,the European Society of Cardiology (ESC) released the 2024 edition of the Guidelines for the Management of Peripheral Arterial and Aortic Diseases. This comprehensive guideline provides detailed recommendations on the diagnosis and treatment strategies for peripheral arterial and aortic diseases (PAAD). It covers topics such as the evaluation and screening,epidemiology,treatment options,and follow-up recommendations of PAAD. With the increasing prevalence of unhealthy lifestyles and the aging population,arterial diseases have become one of the major health threats to residents in China. The detailed recommendations in this edition can be integrated with domestic guidelines to offer feasible and optimal clinical practice strategies for vascular surgeons. This article summarizes the key points and updates of the latest guideline to serve as a reference for domestic scholars.

Tumor has become the major reasons cause of death,and its vaccine has become the effective tracts of treatment and prevention by enhancing the immune response of patients.However,most vaccines which are recombination subunit protein antigens are poorly immunogenic and difficult to induce a robust immune response in patients with compromised immune systems,resulting in poor marketing approval.The core component of the vaccine adjuvant can greatly enhance the strength,speed and duration of the immune response,thus becoming the key to the development of an ideal tumor vaccine.Most tumor vaccines are combined with tradition adjuvant such as aluminum,MF59 and AS adjuvant,but their products and patents are monopolized by large foreign companies.We found that natural adjuvants have many unique advantages,such as good biocompatibility and biodegradability,promoting the maturation of dendritic cell and the secretion of immune cytokines,significantly enhancing the tumor vaccine immune response,etc.In this paper,the application and future development of natural polysaccharides,saponins,flavonoid and plant virus-like particles in cancer vaccines were reviewed,which may lay a solid foundation for the development of the original and innovative adjuvants with domestic independent intellectual property rights.