Research on immune checkpoints such as programmed death protein-1(PD-1)and cytotoxic T lymphocyte antigen-4(CTLA-4)has provided new directions for tumor treatment.V-domain immunoglobulin suppressor of T-cell activation(VISTA)is an emerging immune checkpoint within the B7 family.Functioning as both a ligand and a receptor,VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells,myeloid cells and T lymphocytes.It plays a crucial role in regulating autoimmunity,inflammatory response and tumor immunity.The non-redundant interactions between VISTA and other immune checkpoints,such as PD-1,may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance.This review summarizes the recent research progress on VISTA in hematological tumors,aiming to provide new insights into its application in the treatment of these malignancies.

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

Objective:To investigate the correlation between vasoactive-inotropic score and 30-day mortality after surgery in acute Stanford type A aortic dissection(ATAAD) patients.Methods:The clinical data of 242 patients with ATAAD who underwent surgical treatment was retrospectively analyzed between November 2015 and May 2024. There were 172 males and 70 females. The average age was(53.1±11.9) years, ranging from 28 to 85 years. Patients were divided into death group(18 cases) and survival group(224 cases) according to the 30-day outcomes after surgery. The VIS at different time points and perioperative indexes of two groups of patients were analyzed, and multivariate logistic regression was used to analyze the risk factors of 30-day mortality after surgery in ATAAD patients. The receiver operating characteristic curve( ROC) was drawn to evaluate the predictive value of vasoactive-inotropic score. Results:Among 242 ATAAD patients, 18 patients died within 30 days after surgery, with a mortality rate of 7.4%. The age, incidence of pericardial tamponade/cardiogenic shock, incidence of malperfusion syndrome, cardiopulmonary bypass time, red blood cell transfusion intraoperative and in 24 hours postoperatively, ventilator assisted time, and incidence of major postoperative complications of patients in the death group were significantly higher than those in the survival group( P<0.05). The VIS of the death group was significantly higher than that of the survival group at all time points( P<0.05). The area under the receiver operating characteristic curve( AUC) of VIS for predicting death at each time point was greater than 0.500( P<0.05), with the highest AUC(0.906) of the second 24 hours(VISmax48h) in ICU. The optimal cut off value was determined to be 9, with a sensitivity of 0.944 and a specificity of 0.821. Logistic regression analysis showed that the VISmax48h of the second 24 hours in ICU was an independent risk factor for 30-day mortality after surgery in ATAAD patients( OR=1.462, 95% CI: 1.230-1.737, P<0.05). Conclusion:When VISmax48h≥9, patients with ATAAD have an increased risk of mortality after surgery. VISmax48h, cardiopulmonary bypass time, and red blood cell transfusion intraoperative in 24 hours postoperatively are independent risk factors for the 30-day mortality of ATAAD patients.

Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.

[Purpose]To analyze the trends in pancreatic cancer mortality and disease burden among residents in Shanghai Pudong New Area from 2002 to 2022,and to investigate the effects of age,period,and birth cohort on mortality risk.[Methods]Data on pancreatic cancer deaths among residents of Pudong New Area from 2002 to 2022 were collected through the Shanghai Population Cause of Death Registration System.The crude mortality rate,age-standardized mortality rate by Chinese standard population(ASMRC),potential years of life lost(PYLL),potential years of life lost rate(PYLLR),and average years of life lost(AYLL)were calculated.Joinpoint regression was applied to calculate the average annual percentage change(AAPC)for analyzing the changing trend of the mortality rate of pancreatic cancer.The age-period-cohort model was applied with R 4.4.1 to analyze the age,period,and cohort effects on the mortality risk of pancreatic cancer.[Results]The crude mortality rate of pancreatic cancer among residents in Pudong New Area increased from 10.42/105 in 2002 to 18.73/105 in 2022,showing a significant upward trend(AAPC=2.90％,P＜0.001);the ASMRC was generally stable(AAPC=-0.05％,P=0.775).The crude mortality rate of males(17.09/105)was higher than that of females(13.75/105),and both showed an upward trend(AAPC=3.05％and 2.75％respectively,both P＜0.001).After the age of 40,the mortality rate of pancreatic cancer increased significantly with the growth of age in both sexes.The PYLL was 31 347 person-years,showing an upward trend(AAPC=1.83％,P＜0.001),and the AYLL was 3.59 years,showing a downward trend(AAPC=-2.45％,P＜0.001).The age effect showed that the mortality risk of pan-creatic cancer was increased with age;the period effect showed that the mortality risk decreased from 2002 to 2016 and then increased;the cohort effect showed that the mortality risk increased with the advancement of the birth cohort.[Conclusion]From 2002 to 2022,the crude mortality rate of pancreatic cancer in Pudong New Area showed an upward trend,and the mortality rate of males was higher than that of females.The mortality risk of pancreatic cancer increases with age,and the later the birth year of the residents,the higher the mortality risk.Early screening should be strengthened for men and the elderly,environmental and lifestyle risk factors should be paid attention to in combination with the characteristics of cohort effect,and the prevention and control strategy for the whole population should be optimized.

Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.

Objective:To investigate the correlation between vasoactive-inotropic score and 30-day mortality after surgery in acute Stanford type A aortic dissection(ATAAD) patients.Methods:The clinical data of 242 patients with ATAAD who underwent surgical treatment was retrospectively analyzed between November 2015 and May 2024. There were 172 males and 70 females. The average age was(53.1±11.9) years, ranging from 28 to 85 years. Patients were divided into death group(18 cases) and survival group(224 cases) according to the 30-day outcomes after surgery. The VIS at different time points and perioperative indexes of two groups of patients were analyzed, and multivariate logistic regression was used to analyze the risk factors of 30-day mortality after surgery in ATAAD patients. The receiver operating characteristic curve( ROC) was drawn to evaluate the predictive value of vasoactive-inotropic score. Results:Among 242 ATAAD patients, 18 patients died within 30 days after surgery, with a mortality rate of 7.4%. The age, incidence of pericardial tamponade/cardiogenic shock, incidence of malperfusion syndrome, cardiopulmonary bypass time, red blood cell transfusion intraoperative and in 24 hours postoperatively, ventilator assisted time, and incidence of major postoperative complications of patients in the death group were significantly higher than those in the survival group( P<0.05). The VIS of the death group was significantly higher than that of the survival group at all time points( P<0.05). The area under the receiver operating characteristic curve( AUC) of VIS for predicting death at each time point was greater than 0.500( P<0.05), with the highest AUC(0.906) of the second 24 hours(VISmax48h) in ICU. The optimal cut off value was determined to be 9, with a sensitivity of 0.944 and a specificity of 0.821. Logistic regression analysis showed that the VISmax48h of the second 24 hours in ICU was an independent risk factor for 30-day mortality after surgery in ATAAD patients( OR=1.462, 95% CI: 1.230-1.737, P<0.05). Conclusion:When VISmax48h≥9, patients with ATAAD have an increased risk of mortality after surgery. VISmax48h, cardiopulmonary bypass time, and red blood cell transfusion intraoperative in 24 hours postoperatively are independent risk factors for the 30-day mortality of ATAAD patients.

[Purpose]To analyze the trends in pancreatic cancer mortality and disease burden among residents in Shanghai Pudong New Area from 2002 to 2022,and to investigate the effects of age,period,and birth cohort on mortality risk.[Methods]Data on pancreatic cancer deaths among residents of Pudong New Area from 2002 to 2022 were collected through the Shanghai Population Cause of Death Registration System.The crude mortality rate,age-standardized mortality rate by Chinese standard population(ASMRC),potential years of life lost(PYLL),potential years of life lost rate(PYLLR),and average years of life lost(AYLL)were calculated.Joinpoint regression was applied to calculate the average annual percentage change(AAPC)for analyzing the changing trend of the mortality rate of pancreatic cancer.The age-period-cohort model was applied with R 4.4.1 to analyze the age,period,and cohort effects on the mortality risk of pancreatic cancer.[Results]The crude mortality rate of pancreatic cancer among residents in Pudong New Area increased from 10.42/105 in 2002 to 18.73/105 in 2022,showing a significant upward trend(AAPC=2.90％,P＜0.001);the ASMRC was generally stable(AAPC=-0.05％,P=0.775).The crude mortality rate of males(17.09/105)was higher than that of females(13.75/105),and both showed an upward trend(AAPC=3.05％and 2.75％respectively,both P＜0.001).After the age of 40,the mortality rate of pancreatic cancer increased significantly with the growth of age in both sexes.The PYLL was 31 347 person-years,showing an upward trend(AAPC=1.83％,P＜0.001),and the AYLL was 3.59 years,showing a downward trend(AAPC=-2.45％,P＜0.001).The age effect showed that the mortality risk of pan-creatic cancer was increased with age;the period effect showed that the mortality risk decreased from 2002 to 2016 and then increased;the cohort effect showed that the mortality risk increased with the advancement of the birth cohort.[Conclusion]From 2002 to 2022,the crude mortality rate of pancreatic cancer in Pudong New Area showed an upward trend,and the mortality rate of males was higher than that of females.The mortality risk of pancreatic cancer increases with age,and the later the birth year of the residents,the higher the mortality risk.Early screening should be strengthened for men and the elderly,environmental and lifestyle risk factors should be paid attention to in combination with the characteristics of cohort effect,and the prevention and control strategy for the whole population should be optimized.

Objective:To construct a multi-sequence MRI radiomics combined with KRAS mutation nomogram model to predict the efficacy of pathological complete response (pCR) in patients with rectal cancer after neoadjuvant chemoradiotherapy.Methods:This study was a case-control study. A total of 126 patients with rectal cancer who were treated with neoadjuvant chemoradiotherapy in the Second Affiliated Hospital of Harbin Medical University from June 2020 to December 2023 were retrospectively collected. The pathological response of the postoperative specimens was graded, with 64 cases of pCR and 62 cases of non-pCR. KRAS gene detection was performed on the pathological tissues before neoadjuvant chemoradiotherapy. Among the patients, 34 cases had KRAS mutants and 92 cases had KRAS wild-types. The 126 patients were randomly divided into a training set and a validation set at a ratio of 8∶2 by the random number method, with 101 and 25 cases, respectively. The difference in KRAS mutation status between the pCR group and the non-pCR group was compared by the χ2 test. The radiomic features were extracted from the baseline T 2WI, diffusion-weighted imaging, and apparent diffusion coefficient images of the patients. The optimal radiomic features were screened out to establish the radiomics model. The radiomics-KRAS joint model was constructed by logistic regression, and a nomogram was drawn. The application efficiency of the model was evaluated by the receiver operating characteristic curve and calibration curve. Results:There was a statistically significant difference in KRAS mutation between the pCR group and the non-pCR group in the training set ( χ2=4.69, P=0.032). Ten radiomics features were screened out in MRI images to establish the radiomics model. In the training set and validation set, the areas under the curve (AUC) of KRAS mutation, radiomics model and radiomics-KRAS nomogram model for evaluating pCR after neoadjuvant chemoradiotherapy were 0.665 (95% CI 0.592-0.757), 0.746 (95% CI 0.651-0.895) and 0.818 (95% CI 0.742-0.934), respectively, and the AUCs of the validation set were 0.613 (95% CI 0.582-0.755), 0.738 (95% CI 0.627-0.839) and 0.833 (95% CI 0.768-0.961), respectively. The results of DeLong test showed that the AUC of radiomics-KRAS nomogram model was higher than that of KRAS mutation and radiomics model, and the difference was statistically significant ( Z=0.58, 0.63, P=0.024, 0.022 in the training set; Z=0.54, 0.61, P=0.018, 0.035 in the validation set). The calibration curve showed that the predicted probability of the radiomics-KRAS nomogram model was consistent with the actual probability. Conclusions:The multi-sequence MRI radiomics combined with the KRAS mutation nomogram model has the best efficacy in predicting pCR in patients with rectal cancer after neoadjuvant chemoradiotherapy, and has good practical application value.