BACKGROUND The impact of racial and regional disparity on younger patients with gastric cancer(GC) remains unclear.AIM To investigate the clinicopathological characteristics, prognostic nomogram, and biological analys...BACKGROUND The impact of racial and regional disparity on younger patients with gastric cancer(GC) remains unclear.AIM To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States.METHODS From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models.RESULTS A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes(P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets(P < 0.01). After stratification by pathological Tumor-Node-Metastasis(pTNM) stage, a survival advantage was observed in China with pathological stage Ⅰ, Ⅲ, and Ⅳ(all P < 0.01), whereas younger GC patients with stage Ⅱ showed no difference(P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles(GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions.CONCLUSION Except for younger cases with pTNM stage Ⅱ, a survival advantage was observed in the China group with pathological stage Ⅰ, Ⅲ, and Ⅳ compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations.展开更多
BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to ...BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.展开更多
Osimertinib is a third-generation epidermal growth factor receptor(EGFR)—tyrosine kinase inhibitors(TKI)selective for both EGFR-TKI sensitizing and T790M resistance mutations.It is also recommended as firstline thera...Osimertinib is a third-generation epidermal growth factor receptor(EGFR)—tyrosine kinase inhibitors(TKI)selective for both EGFR-TKI sensitizing and T790M resistance mutations.It is also recommended as firstline therapy for patients with non-small-cell lung cancer(NSCLC)who have targetable EGFR mutations.[1]Recently,some emerging evidence revealed the significant cardiac toxicity induced by osimertinib.However,osimertinib-induced dilated cardiomyopathy and congestive heart failure has never been reported in China.Here,we report a rare case of dilated cardiomyopathy with heart failure exacerbation which developed during osimertinib treatment.展开更多
BACKGROUND The preoperative total bilirubin-albumin ratio(TBAR)and fibrinogen-albumin ratio(FAR)have been proven to be valuable prognostic factors in various cancers.AIM To detect the prognostic value of TBAR and FAR ...BACKGROUND The preoperative total bilirubin-albumin ratio(TBAR)and fibrinogen-albumin ratio(FAR)have been proven to be valuable prognostic factors in various cancers.AIM To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma(AC)patients who underwent curative pancreaticoduodenectomy.METHODS AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed.The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model.Then,a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis.RESULTS A total of 188 AC patients were enrolled in the current study.The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329,respectively.AC patients were divided into a TBAR-low group(score=0)vs a TBAR-high group(score=1)and a FAR-low group(score=0)vs a FAR-high group(score=1).The total score was calculated as a novel prognostic factor.Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence[score=1 vs score=0:Odds ratio(OR)=0.517,P=0.046;score=2 vs score=0 OR=0.236,P=0.038].In addition,multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients(score=2 vs score=0:Hazard ratio=0.230,P=0.046).CONCLUSION A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy.However,more studies with larger samples are needed to validate this conclusion.展开更多
BACKGROUND Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics,which have a significant impact on prognosis.However,no study has reported the differences betw...BACKGROUND Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics,which have a significant impact on prognosis.However,no study has reported the differences between pancreatic mucinous adenocarcinoma(PMAC)in the head vs the body/tail of the pancreas.AIM To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas.METHODS A total of 2058 PMAC patients from the Surveillance,Epidemiology,and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed.We divided the patients who met the inclusion criteria into pancreatic head group(PHG)and pancreatic body/tail group(PBTG).The relationship between two groups and risk of invasive factors was identified using logistic regression analysis.Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival(OS)and cancer-specific survival(CSS)of two patient groups.RESULTS In total,271 PMAC patients were included in the study.The 1-year,3-year,and 5-year OS rates of these patients were 51.6%,23.5%,and 13.6%,respectively.The 1-year,3-year,and 5-year CSS rates were 53.2%,26.2%,and 17.4%,respectively.The median OS of PHG patients was longer than that of PBTG patients(18 vs 7.5 mo,P<0.001).Compared to PHG patients,PBTG patients had a greater risk of metastases[odds ratio(OR)=2.747,95%confidence interval(CI):1.628-4.636,P<0.001]and higher staging(OR=3.204,95%CI:1.895-5.415,P<0.001).Survival analysis revealed that age<65 years,male sex,low grade(G1-G2),low stage,systemic therapy,and PMAC located at the pancreatic head led to longer OS and CSS(all P<0.05).The location of PMAC was an independent prognostic factor for CSS[hazard ratio(HR)=0.7,95%CI:0.52-0.94,P=0.017].Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage(stage III-IV).CONCLUSION Compared to the pancreatic body/tail,PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.展开更多
BACKGROUND Textbook outcomes(TOs)have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma(AC).AIM To discuss the factors associated with achieving a TO and furt...BACKGROUND Textbook outcomes(TOs)have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma(AC).AIM To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy(PD).METHODS Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified.A TO was defined by R0 resection,examination of≥12 Lymph nodes,no prolonged hospitalization,no intensive care unit treatment,no postoperative complications,and no 30-day readmission or mortality.Cox regression analysis was used to identify the prognostic value of a TO for overall survival(OS)and recurrence-free survival(RFS).Logistic regression was used to identify predictors of a TO.The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010.RESULTS Ultimately,only 24.3%of 272 AC patients achieved a TO.A TO was independently associated with improved OS[hazard ratio(HR):0.443,95%confidence interval(95%CI):0.276-0.711,P=0.001]and RFS(HR:0.379,95%CI:0.228-0.629,P<0.001)in the Cox regression analysis.Factors independently associated with a TO included a year of surgery between 2010 and 2020(OR:4.549,95%CI:2.064-10.028,P<0.001)and N1 stage disease(OR:2.251,95%CI:1.023-4.954,P=0.044).In addition,the TO rate was significantly higher in patients who underwent surgery after 2010(P<0.001)than in those who underwent surgery before 2010.CONCLUSION Only approximately a quarter(24.3%)of AC patients achieved a TO following PD.A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery.Further multicentre research is warranted to better elucidate its impact.展开更多
BACKGROUND The effect of perioperative blood transfusion(PBT)on the prognosis of ampullary carcinoma(AC)is still debated.AIM To explore the impact of PBT on short-term safety and long-term survival in AC patients who ...BACKGROUND The effect of perioperative blood transfusion(PBT)on the prognosis of ampullary carcinoma(AC)is still debated.AIM To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy.METHODS A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital,Chinese Academy of Medical Sciences,were retrospectively analyzed.We used Cox proportional hazard regression to identify prognostic factors of overall survival(OS)and recurrencefree survival(RFS)and the Kaplan-Meier method to analyze survival information.RESULTS A total of 144(56%)of 257 patients received PBT.The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics.Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not.Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS.We performed Kaplan-Meier analysis according to subgroups of T stage,and subgroup analysis indicated that PBT might be associated with worse OS(P<0.05)but not RFS in AC of stage T1.CONCLUSION We found that PBT might be associated with decreased OS in early AC,but more validation is needed.The reasonable use of transfusion might be helpful to improve OS.展开更多
Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons. Abnormal protein aggregation and impaired protein degradation are believed to contribute t...Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons. Abnormal protein aggregation and impaired protein degradation are believed to contribute to the pathogenesis of this disease. Our previous studies showed that an autophagic flux defect is involved in motor neuron degeneration in the SOD1G93 A mouse model of ALS. Histone deacetylase 6(HDAC6) is a class II deacetylase that promotes autophagy by inducing the fusion of autophagosomes to lysosomes. In the present study, we showed that HDAC6 expression was decreased at the onset of disease and became extremely low at the late stage in ALS mice. Using lentivirus-HDAC6 gene injection, we found that HDAC6 overexpression prolonged the lifespan and delayed the motor neuron degeneration in ALS mice. Moreover, HDAC6 induced the formation of autolysosomes and accelerated the degradation of SOD1 protein aggregates in the motor neurons of ALS mice. Collectively, our results indicate that HDAC6 has neuroprotective effects in an animal model of ALS by improving the autophagic flux in motor neurons, and autophagosome-lysosome fusion might be a therapeutic target for ALS.展开更多
To emphasize the early diagnosis and treatment of anti-N-methyl-d-aspartate-receptor (NMDAR) autoimmune encephalitis, a rare clinical condition, teratoma-related, anti-NMDAR encephalitis should be suspected if young p...To emphasize the early diagnosis and treatment of anti-N-methyl-d-aspartate-receptor (NMDAR) autoimmune encephalitis, a rare clinical condition, teratoma-related, anti-NMDAR encephalitis should be suspected if young patients present with psychiatric, movement, and sensory symptoms. Early diagnosis and treatment can decrease the mortality and disability rate.展开更多
基金supported by the National Nat-ural Science Foundation of China(22162006)the China Postdoctoral Science Foundation(2021M 691366)the Natural Science Foundation of Shanxi Province(20210302124473).
基金National Key R&D Program of China,No.2017YFC0908300.
文摘BACKGROUND The impact of racial and regional disparity on younger patients with gastric cancer(GC) remains unclear.AIM To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States.METHODS From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models.RESULTS A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes(P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets(P < 0.01). After stratification by pathological Tumor-Node-Metastasis(pTNM) stage, a survival advantage was observed in China with pathological stage Ⅰ, Ⅲ, and Ⅳ(all P < 0.01), whereas younger GC patients with stage Ⅱ showed no difference(P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles(GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions.CONCLUSION Except for younger cases with pTNM stage Ⅱ, a survival advantage was observed in the China group with pathological stage Ⅰ, Ⅲ, and Ⅳ compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations.
文摘BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.
基金National Science and Technology Innovation 2030 of China(2021ZD0111000).
文摘Osimertinib is a third-generation epidermal growth factor receptor(EGFR)—tyrosine kinase inhibitors(TKI)selective for both EGFR-TKI sensitizing and T790M resistance mutations.It is also recommended as firstline therapy for patients with non-small-cell lung cancer(NSCLC)who have targetable EGFR mutations.[1]Recently,some emerging evidence revealed the significant cardiac toxicity induced by osimertinib.However,osimertinib-induced dilated cardiomyopathy and congestive heart failure has never been reported in China.Here,we report a rare case of dilated cardiomyopathy with heart failure exacerbation which developed during osimertinib treatment.
文摘BACKGROUND The preoperative total bilirubin-albumin ratio(TBAR)and fibrinogen-albumin ratio(FAR)have been proven to be valuable prognostic factors in various cancers.AIM To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma(AC)patients who underwent curative pancreaticoduodenectomy.METHODS AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed.The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model.Then,a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis.RESULTS A total of 188 AC patients were enrolled in the current study.The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329,respectively.AC patients were divided into a TBAR-low group(score=0)vs a TBAR-high group(score=1)and a FAR-low group(score=0)vs a FAR-high group(score=1).The total score was calculated as a novel prognostic factor.Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence[score=1 vs score=0:Odds ratio(OR)=0.517,P=0.046;score=2 vs score=0 OR=0.236,P=0.038].In addition,multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients(score=2 vs score=0:Hazard ratio=0.230,P=0.046).CONCLUSION A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy.However,more studies with larger samples are needed to validate this conclusion.
文摘BACKGROUND Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics,which have a significant impact on prognosis.However,no study has reported the differences between pancreatic mucinous adenocarcinoma(PMAC)in the head vs the body/tail of the pancreas.AIM To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas.METHODS A total of 2058 PMAC patients from the Surveillance,Epidemiology,and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed.We divided the patients who met the inclusion criteria into pancreatic head group(PHG)and pancreatic body/tail group(PBTG).The relationship between two groups and risk of invasive factors was identified using logistic regression analysis.Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival(OS)and cancer-specific survival(CSS)of two patient groups.RESULTS In total,271 PMAC patients were included in the study.The 1-year,3-year,and 5-year OS rates of these patients were 51.6%,23.5%,and 13.6%,respectively.The 1-year,3-year,and 5-year CSS rates were 53.2%,26.2%,and 17.4%,respectively.The median OS of PHG patients was longer than that of PBTG patients(18 vs 7.5 mo,P<0.001).Compared to PHG patients,PBTG patients had a greater risk of metastases[odds ratio(OR)=2.747,95%confidence interval(CI):1.628-4.636,P<0.001]and higher staging(OR=3.204,95%CI:1.895-5.415,P<0.001).Survival analysis revealed that age<65 years,male sex,low grade(G1-G2),low stage,systemic therapy,and PMAC located at the pancreatic head led to longer OS and CSS(all P<0.05).The location of PMAC was an independent prognostic factor for CSS[hazard ratio(HR)=0.7,95%CI:0.52-0.94,P=0.017].Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage(stage III-IV).CONCLUSION Compared to the pancreatic body/tail,PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.
文摘BACKGROUND Textbook outcomes(TOs)have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma(AC).AIM To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy(PD).METHODS Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified.A TO was defined by R0 resection,examination of≥12 Lymph nodes,no prolonged hospitalization,no intensive care unit treatment,no postoperative complications,and no 30-day readmission or mortality.Cox regression analysis was used to identify the prognostic value of a TO for overall survival(OS)and recurrence-free survival(RFS).Logistic regression was used to identify predictors of a TO.The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010.RESULTS Ultimately,only 24.3%of 272 AC patients achieved a TO.A TO was independently associated with improved OS[hazard ratio(HR):0.443,95%confidence interval(95%CI):0.276-0.711,P=0.001]and RFS(HR:0.379,95%CI:0.228-0.629,P<0.001)in the Cox regression analysis.Factors independently associated with a TO included a year of surgery between 2010 and 2020(OR:4.549,95%CI:2.064-10.028,P<0.001)and N1 stage disease(OR:2.251,95%CI:1.023-4.954,P=0.044).In addition,the TO rate was significantly higher in patients who underwent surgery after 2010(P<0.001)than in those who underwent surgery before 2010.CONCLUSION Only approximately a quarter(24.3%)of AC patients achieved a TO following PD.A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery.Further multicentre research is warranted to better elucidate its impact.
文摘BACKGROUND The effect of perioperative blood transfusion(PBT)on the prognosis of ampullary carcinoma(AC)is still debated.AIM To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy.METHODS A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital,Chinese Academy of Medical Sciences,were retrospectively analyzed.We used Cox proportional hazard regression to identify prognostic factors of overall survival(OS)and recurrencefree survival(RFS)and the Kaplan-Meier method to analyze survival information.RESULTS A total of 144(56%)of 257 patients received PBT.The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics.Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not.Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS.We performed Kaplan-Meier analysis according to subgroups of T stage,and subgroup analysis indicated that PBT might be associated with worse OS(P<0.05)but not RFS in AC of stage T1.CONCLUSION We found that PBT might be associated with decreased OS in early AC,but more validation is needed.The reasonable use of transfusion might be helpful to improve OS.
基金supported by grants from the National Natural Science Foundation of China (81200977)the Shanghai Natural Science Foundation (14ZR1446400)+2 种基金Shanghai Rising-Star Program (15QA1403000)the PhD Innovation Fund of Shanghai Jiaotong University School of Medicine (BXJ 201218)the PhD Tutor Fund of the Ministry of Education of China (20120073110077)
文摘Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons. Abnormal protein aggregation and impaired protein degradation are believed to contribute to the pathogenesis of this disease. Our previous studies showed that an autophagic flux defect is involved in motor neuron degeneration in the SOD1G93 A mouse model of ALS. Histone deacetylase 6(HDAC6) is a class II deacetylase that promotes autophagy by inducing the fusion of autophagosomes to lysosomes. In the present study, we showed that HDAC6 expression was decreased at the onset of disease and became extremely low at the late stage in ALS mice. Using lentivirus-HDAC6 gene injection, we found that HDAC6 overexpression prolonged the lifespan and delayed the motor neuron degeneration in ALS mice. Moreover, HDAC6 induced the formation of autolysosomes and accelerated the degradation of SOD1 protein aggregates in the motor neurons of ALS mice. Collectively, our results indicate that HDAC6 has neuroprotective effects in an animal model of ALS by improving the autophagic flux in motor neurons, and autophagosome-lysosome fusion might be a therapeutic target for ALS.
文摘To emphasize the early diagnosis and treatment of anti-N-methyl-d-aspartate-receptor (NMDAR) autoimmune encephalitis, a rare clinical condition, teratoma-related, anti-NMDAR encephalitis should be suspected if young patients present with psychiatric, movement, and sensory symptoms. Early diagnosis and treatment can decrease the mortality and disability rate.
