AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristi...AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.展开更多
BACKGROUND： Both animal experiments and clinical studies have shown that basic fibroblast growth factor （bFGF） and danshen （Salvia miltiorrhiza） can exhibit protective effects on ischemia-reperfusion cerebral inj...BACKGROUND： Both animal experiments and clinical studies have shown that basic fibroblast growth factor （bFGF） and danshen （Salvia miltiorrhiza） can exhibit protective effects on ischemia-reperfusion cerebral injury. OBJECTIVE： To test whether bFGF and danshen can protect cerebral injury induced by exposure to repeated, high, positive acceleration （＋Gz） in an animal model and to analyze the possible mechanisms. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was performed at the Research Center for Molecular Biology, Air-force General Hospital of Chinese PLA from April to August 2000. MATERIALS： A total of 20 clean grade, healthy, Sprague Dawley rats of both genders, weighing （200 ± 15） g, were provided by our experimental animal center. Rats were randomly divided into 5 groups： the control group, ＋Gz exposure group, bFGF group, danshen group, and saline group, with 4 animals per group. bFGF （Beijing Bailuyuan Biotechnology Co. Ltd.） and danshen solution （Shanghai Zhongxi Pharmaceutical Co. Ltd.） were used. METHODS： All rats were fixed on a rotary arm of a centrifugal apparatus （2 m in radius） with their heads oriented towards the center of the apparatus. Except for rats in the control group, the value of ＋Gz exposure was ＋14 Gz with an acceleration rate of 1.5 G/s. The peak force lasted for 45 seconds. ＋Gz exposure was performed three times with intervals of 30 minutes. Rats in the control group received the same ＋Gz procedure, but the G value was ＋1 Gz. Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg bFGF or 15 g/kg danshen solution, respectively, at 30 minutes prior to centrifugation and immediately after centrifugation. Rats in saline group were injected with the same volume of saline. Six hours after exposure, rats were decapitated. One hemisphere was preserved in liquid nitrogen for RNA extraction and the other was processed for apoptosis detection. MAIN OUTCOME MEASURES： mRNA levels of bcl-2 and p53 were measured by semi-quantitative reverse-transcription polymerase chain reaction. Apoptotic cell death was detected by terminal deoxynuleotidyl transferase-mediated dUTP nick end labeling. RESULTS： Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated ＋Gz exposures, bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death. CONCLUSION： The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated ＋Gz exposures. Apoptosis is, therefore, one of the molecular mechanisms of brain damage induced by repeated ＋Gz exposures, bFGF and danshen were of the equal potency in preventing brain injury induced by repeated ＋Gz exposures.展开更多
目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭...目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭患者为研究对象,按随机数字表法分为对照组和观察组,各43例。对照组予以常规治疗降糖及抗心力衰竭治疗,观察组在对照组基础上增加达格列净治疗。比较两组治疗前、治疗6个月后的血糖[糖化血红蛋白(HbA1c)、空腹血糖、餐后2 h血糖(2 h PG)]、血脂[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)]、心功能[左心室射血分数(LVEF)、血浆N端脑钠肽前体(NT-proBNP)、6 min步行试验(6MWT)]、血清指标[白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、sST2]水平及心血管事件及不良反应发生率。结果治疗6个月后,观察组的HbA1c、空腹血糖、2 h PG、总胆固醇、甘油三酯、LDL-C水平分别为(6.65±0.73)%、(6.25±1.54)mmol/L、(7.88±1.35)mmol/L、(3.87±0.85)mmol/L、(1.52±0.46)mmol/L、(2.41±0.63)mmol/L,均明显低于对照组[(7.07±0.85)%、(7.16±1.49)mmol/L、(8.82±1.48)mmol/L、(4.24±0.82)mmol/L、(1.73±0.51)mmol/L、(2.69±0.61)mmol/L],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的LVEF、6MWT水平分别为(52.28±3.43)%、(424.87±72.58)m,均明显高于对照组[(50.79±3.25)%、(367.52±74.43)m],血浆NT-proBNP水平为(1778.65±224.37)pg/mL,低于对照组[(2943.41±256.22)pg/mL],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的血清IL-1β、TNF-α、sST2水平分别为(6.60±1.14)pg/mL、(22.15±4.30)ng/L、(0.42±0.13)g/L,均明显低于对照组[(7.19±1.39)pg/mL、(29.68±5.24)ng/L、(0.50±0.16)g/L],差异均有统计学意义(P<0.05)。观察组心血管事件总发生率为9.30%,低于对照组(25.58%),差异有统计学意义(P<0.05)。两组均无严重不良反应发生。结论在使用常规降糖、抗心力衰竭治疗2型糖尿病伴心力衰竭患者基础上增加达格列净可有效降低其血糖、血脂及血清IL-1β、TNF-α、sST2水平,减少心血管事件的发生,具有一定心血管保护作用。展开更多
文摘AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann's HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann's HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but low consistency was observed between IHC2+ and FISH(40.00%).The positivity rates in intestinal type and well-differentiated gastric cancer were higher than those in diffuse/mixed type and poorly-differentiated gastric cancer respectively(28.57% vs 13.43%,P = 0.0103;37.25% vs 11.64%,P < 0.0001),but were not correlated with gender,age,tumor location or TNM stage,depth of invasion,lymph node metastases and distant metastasis.In poorly-differentiated gastric cancer patients,those without lymph node metastasis showed a higher HER2 positivity rate than those with lymph node metastasis(26.47% vs 7.14%,P = 0.0021).This association was not present in thosepatients with well-differentiated gastric cancer(28.57% vs 43.33%,P = 0.2832).Within our patient cohort,26 cases were lost to follow-up.The median survival time for the remaining 171 patients was 18 mo.The median survival times of the HER2 positive and negative groups were 17 and 18.5 mo respectively.Overall survival was not significantly different between HER2-positive and negative groups(χ 2 = 0.9157,P = 0.3386),but in patients presenting well-differentiated tumors,the overall survival of the HER2-positive group was significantly worse than that of the HER2-negative group(P = 0.0123).In contrast,patients with poorly differentiated and diffuse/mixed subtype gastric cancers showed no significant differences in overall survival associated with HER2.Furthermore,the median survival time of the HER2 positive group did not show any statistically significant differences when compared to the subgroups of gender,age,tumor location,TNM classification,lymph node metastases and distant metastasis.CONCLUSION:Patients with intestinal type gastric cancer(GC),well-differentiated GC and poorly-differentiated GC without lymph node metastasis,may all represent suitable candidates for targeted therapy using Herceptin.
文摘BACKGROUND： Both animal experiments and clinical studies have shown that basic fibroblast growth factor （bFGF） and danshen （Salvia miltiorrhiza） can exhibit protective effects on ischemia-reperfusion cerebral injury. OBJECTIVE： To test whether bFGF and danshen can protect cerebral injury induced by exposure to repeated, high, positive acceleration （＋Gz） in an animal model and to analyze the possible mechanisms. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was performed at the Research Center for Molecular Biology, Air-force General Hospital of Chinese PLA from April to August 2000. MATERIALS： A total of 20 clean grade, healthy, Sprague Dawley rats of both genders, weighing （200 ± 15） g, were provided by our experimental animal center. Rats were randomly divided into 5 groups： the control group, ＋Gz exposure group, bFGF group, danshen group, and saline group, with 4 animals per group. bFGF （Beijing Bailuyuan Biotechnology Co. Ltd.） and danshen solution （Shanghai Zhongxi Pharmaceutical Co. Ltd.） were used. METHODS： All rats were fixed on a rotary arm of a centrifugal apparatus （2 m in radius） with their heads oriented towards the center of the apparatus. Except for rats in the control group, the value of ＋Gz exposure was ＋14 Gz with an acceleration rate of 1.5 G/s. The peak force lasted for 45 seconds. ＋Gz exposure was performed three times with intervals of 30 minutes. Rats in the control group received the same ＋Gz procedure, but the G value was ＋1 Gz. Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg bFGF or 15 g/kg danshen solution, respectively, at 30 minutes prior to centrifugation and immediately after centrifugation. Rats in saline group were injected with the same volume of saline. Six hours after exposure, rats were decapitated. One hemisphere was preserved in liquid nitrogen for RNA extraction and the other was processed for apoptosis detection. MAIN OUTCOME MEASURES： mRNA levels of bcl-2 and p53 were measured by semi-quantitative reverse-transcription polymerase chain reaction. Apoptotic cell death was detected by terminal deoxynuleotidyl transferase-mediated dUTP nick end labeling. RESULTS： Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated ＋Gz exposures, bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death. CONCLUSION： The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated ＋Gz exposures. Apoptosis is, therefore, one of the molecular mechanisms of brain damage induced by repeated ＋Gz exposures, bFGF and danshen were of the equal potency in preventing brain injury induced by repeated ＋Gz exposures.
文摘目的探究达格列净联合常规治疗对2型糖尿病伴心力衰竭患者的心血管保护作用及对血清炎症因子和可溶性生长刺激表达基因2(sST2)水平的影响。方法前瞻性选取2020年9月至2022年8月江苏省昆山市第一人民医院收治的86例2型糖尿病伴心力衰竭患者为研究对象,按随机数字表法分为对照组和观察组,各43例。对照组予以常规治疗降糖及抗心力衰竭治疗,观察组在对照组基础上增加达格列净治疗。比较两组治疗前、治疗6个月后的血糖[糖化血红蛋白(HbA1c)、空腹血糖、餐后2 h血糖(2 h PG)]、血脂[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)]、心功能[左心室射血分数(LVEF)、血浆N端脑钠肽前体(NT-proBNP)、6 min步行试验(6MWT)]、血清指标[白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、sST2]水平及心血管事件及不良反应发生率。结果治疗6个月后,观察组的HbA1c、空腹血糖、2 h PG、总胆固醇、甘油三酯、LDL-C水平分别为(6.65±0.73)%、(6.25±1.54)mmol/L、(7.88±1.35)mmol/L、(3.87±0.85)mmol/L、(1.52±0.46)mmol/L、(2.41±0.63)mmol/L,均明显低于对照组[(7.07±0.85)%、(7.16±1.49)mmol/L、(8.82±1.48)mmol/L、(4.24±0.82)mmol/L、(1.73±0.51)mmol/L、(2.69±0.61)mmol/L],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的LVEF、6MWT水平分别为(52.28±3.43)%、(424.87±72.58)m,均明显高于对照组[(50.79±3.25)%、(367.52±74.43)m],血浆NT-proBNP水平为(1778.65±224.37)pg/mL,低于对照组[(2943.41±256.22)pg/mL],差异均有统计学意义(P<0.05)。治疗6个月后,观察组的血清IL-1β、TNF-α、sST2水平分别为(6.60±1.14)pg/mL、(22.15±4.30)ng/L、(0.42±0.13)g/L,均明显低于对照组[(7.19±1.39)pg/mL、(29.68±5.24)ng/L、(0.50±0.16)g/L],差异均有统计学意义(P<0.05)。观察组心血管事件总发生率为9.30%,低于对照组(25.58%),差异有统计学意义(P<0.05)。两组均无严重不良反应发生。结论在使用常规降糖、抗心力衰竭治疗2型糖尿病伴心力衰竭患者基础上增加达格列净可有效降低其血糖、血脂及血清IL-1β、TNF-α、sST2水平,减少心血管事件的发生,具有一定心血管保护作用。
