Objective To investigate the effect of transplantation of CXC receptor 4 (CXCR4)gene-modified bone marrow mesenchymal stem cells (BMSCs) on repairment of carotid injure in rats.Methods BMSCs were cultured and transfected with lentivirus vector carrying CXCR4 gene to generate CXCR4 gene-modified BMSCs (CXCR4-BMSCs).CXCR4 expression was detected by Western blot.Rat model of carotid artery balloon injury was established.Rats were randomly divided into the PBS control group (n=12),CXCR4-BMSCs group (n=12) and BMSCs group (n=12).Two weeks after transplantation,the injured arteries were obtained.The homing of BMSCs was detected by immunofluorescence with green fluorescent protein (GFP).Platelet endothelial cell adhesion molecule (CD31) expression was detected by immunofluorescence staining.At 4 weeks after transplantation,proliferating cell nuclear antigen (PCNA) expression was determined by immunohistochemical staining,and the vascular morphological changes were observed by hematoxylineosin staining (HE).Results Compared with the control and BMSCs groups,the protein level of CXCR4 was increased in CXCR4-BMSCs group (both P＜0.05).The percentage of GFP-positive cells homing were much more in CXCR4-BMSCs group than in BMSCs group [(58.8±4.4)％ vs.(36.2±5.0) ％,P＜0.05].The CD31 expression were higher in CXCR4-BMSCs group than in BMSCs group [(58.8±4.3)％ vs.(28.8±4.2)％,P＜0.05].Compared to the control group,the PCNA expression was decreased in CXCR4-BMSCs and BMSCs groups [(21.0±4.2) ％,(36.5±4.9) ％vs.(78.3±3.5) ％,both P＜0.05].There was a significant difference in PCNA expression between the CXCR4-BMSCsgroupandBMSCs group [(21.0±4.2)％vs.(36.5±4.9)％,P＜0.05].The neointimal area and the ratio of neointimal/medial area were decreased in CXCR4 BMSCs and BMSCs group as compared with the control group [(0.205±0.018) mm2,(0.323±0.071) mm2 vs.(0.536 ± ±0.054) mm2; (1.039±0.123),(1.660±0.404) vs.(2.460±0.328); all P＜0.05],and there were significant differences in neointimal area and the ratio of neointimal/medial area in CXCR4-BMSCs group and BMSCs group [[(0.205±0.018) mm2 vs.(0.323±0.071) mm2,(1.039±0.123)vs.(1.660±0.404),both P＜0.05].Conclusions CXCR4 gene-modified BMSCs may increase the CXCR4 expression in BMSCs.CXCR4-BMSCs transplantation is more effective than BMSCs transplantation in increasing BMSCs homing capacity,reducing the reendothelialization and vascular restenosis.

This study investigated the intracellular localization of asparagine synthetase (ASNS) in the relation with chemoresistance in leukemia. pIRES-GFP-ASNS-Flag/Neo expression vector was transiently tansfected into SK-N-MC cells and 297T cells respectively. Immunofluorescence and Western blot analysis were performed for cellular localization of ASNS respectively. U937 cells were treated with L-asparaginase for 48 h and examined for endogenous ASNS expression on plasma membrane by immunofluorescence staining. Immunofluorescence staining showed that the transiently expressed ASNS was partly localized on transfected-SK-N-MC cell surface. Moreover, Western blotting exhibited that ASNS expressed both in cytosol and on plasma membrane of transfected-293T cells. Immunofluorescence staining with anti-ASNS-specific monoclonal antibody revealed that endogenous ASNS was localized on the plasma membrane of U937 cells, except for its distribution in the cytosol. In addition, ASNS exhibited a higher expression on plasma membrane after treatment with L-asparaginase as compared with the untreated cells. It was concluded that the subcellular translocation of ASNS may play an important role in L-asparaginase resistance in leukemia cells.

This study investigated the intracellular localization of asparagine synthetase (ASNS) in the relation with chemoresistance in leukemia.pIRES-GFP-ASNS-Flag/Neo expression vector was transiently tansfected into SK-N-MC cells and 297T cells respectively.Immunofluorescence and Western blot analysis were performed for cellular localization of ASNS respectively.U937 cells were treated with L-asparaginase for 48 h and examined for endogenous ASNS expression on plasma membrane by immunofluorescence staining.Immunofluorescence staining showed that the transiently expressed ASNS was partly localized on transfected-SK-N-MC cell surface.Moreover,Western blotting exhibited that ASNS expressed both in cytosol and on plasma membrane of transfected-293T cells.Immunofluo-rescence staining with anti-ASNS-specific monoclonal antibody revealed that endogenous ASNS was localized on the plasma membrane of U937 cells,except for its distribution in the cytosol.In addition,ASNS exhibited a higher expression on plasma membrane after treatment with L-asparaginase as compared with the untreated cells.It was concluded that the subcellular translocation of ASNS may play an important role in L-asparaginase resistance in leukemia cells.

Objective To evaluate the effect of surgery-radiotherapy interval (SRI) on clinical prognosis of locally advanced stage c Ⅱ-Ⅲ breast cancer patients treated with neoadjuvant chemtherapy and modified radical mastectomy.Methods Clinical data of 1 087 breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy from 11 hospitals in China were retrospectively analyzed.The optimal threshold value of SRI upon clinical prognosis was determined by maxstat method.The effect of SRI on clinical prognosis was evaluated by using multivariate Cox regression analysis and propensity score matching (PSM).Results The median follow-up time was 72.9 months.The 5-year disease-free survival (DFS) and overall survival (OS) rates were 68.1％ and 81.8％.All patients were divided into SRI ≤18 weeks (n=917) and SRI＞ 18 weeks groups (n=170).Multivariate Cox regression analysis demonstrated that hormone receptor status (P＜0.001),pathological T stage (P＜0.001),pathological N stage (P＜0.001) and SRI (P=0.023) were independent influencing factors of DFS.Hormone receptor status (P=0.013),pathological T stage (P=0.006),pathological N stage (P＜0.001),endocrine therapy (P=0.013) and SRI (P=0.001) were significantly associated with OS.After balancing the clinical and pathological factors with PSM,patients with SRI＜ 18 weeks had superior DFS and OS to those with SRI＞ 18 weeks.Conclusions SRI affects the clinical prognosis of locally advanced breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy.Radiotherapy should be performed within 18 weeks after mastectomy.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.