Objective: To explore the risk factors of allogeneic blood transfusion during lung transplant surgery and prognostic effects of transfusion by analyzing the basic data, surgical details, laboratory tests results, and intraoperative blood transfusion details during the perioperative period of lung transplant, so as to guide clinical blood use. Methods: A retrospective analysis was conducted on the data of 319 patients who underwent lung transplantation surgery in our hospital from January 2022 to December 2023. The patients were divided into a non-transfusion group (n=70) and a transfusion group (n=249) based on their intraoperative blood transfusion status. The clinical data, surgical details, perioperative laboratory results and other relevant preoperative and postoperative parameters were compared between the two groups, and the postoperative prognosis (improvement, non-recovery, and death) was analyzed. Results: After comparison between the two groups of patients, it was found that the non-transfusion group had higher levels of preoperative Hb (g/L)(144.41±17.66 vs 129.78±20.44), preoperative Hct [43.25(40.23, 47.5) vs 40.7(37, 43.55)], preoperative TBIL (μmol/L)[11.45(9.15, 15.3)vs 9.9(6.88, 13.33)], and postoperative PLT (×10 /L)(167.74±64.43 vs 132.37±54.84) than the transfusion group (all P<0.05). The non-transfusion group had lower levels of preoperative pCO (mmHg)[41.4(37.4, 45.8)vs 45.3(40, 52.48)], postoperative TBIL (μmol/L)[25.45(17.68, 33.95)vs 30.8(21.55, 43.05)], postoperative pH (7.41±0.09 vs 7.45±0.10), bilateral lung transplantation [27(38.6%) vs 157(63.1%)], surgical duration (h) [5(4, 7)vs 6.5(5, 8)], use of ECMO [52(74.3%) vs 232(93.2%)], and intraoperative blood loss (mL)[600(500, 800)vs 1 000(800, 1 500)] compared to the transfusion group (all P<0.05). The items with P<0.1 in the compared indicators were included in the binary logistic regression analysis, and the results showed that bilateral lung transplantation, intraoperative blood loss, preoperative TBIL, postoperative PLT, postoperative TBIL, preoperative pCO2, and postoperative pH were significantly correlated with whether blood transfusion was performed (P<0.05). The P values of the Chi-square test for postoperative improvement and mortality in the non transfusion group and transfusion group were both greater than 0.05, indicating no statistically significant difference in the prognosis rate between the two groups of patients. Conclusion: Bilateral lung transplantation, intraoperative blood loss, preoperative TBIL, and preoperative pCO are risk factors for blood transfusion during lung transplantation. Intraoperative blood transfusion has a significant impact on postoperative PLT, postoperative TBIL, and postoperative pH indicators, but has no significant effect on prognosis. A comprehensive evaluation of laboratory indicators and surgical details can help developing blood transfusion strategies more effectively.

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.

Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.