BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic a...BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.展开更多
The heat shock proteins （HSPs） 70 and HSP 27 expression in patients with non-small cell lung cancer （NSCLC） was studied and the relation.ship between HSP 70 and HSP 27 with the clinicopathological features of NSCL...The heat shock proteins （HSPs） 70 and HSP 27 expression in patients with non-small cell lung cancer （NSCLC） was studied and the relation.ship between HSP 70 and HSP 27 with the clinicopathological features of NSCLC was investigated. The expression of HSP 70 and HSP 27 was detected in tumor tissues from 60 patients with NSCLC by S-P immunohistochemistry. The findings were analyzed in combination with the histological types, histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history and gender. The results showed that of the 60 NSCLC tissue specimens studied, the immunoreactivity of HSP 70 and HSP 27 was detected in 47 （78.3 %） and 43 （71.7 %） specimens, respectively. A positive correlation was found between the overexpression of HSP 70 and HSP 27. The histopathological differentiation, lymph node metastasis, clinical stages and smoking history were correlated to the expression of HSP 70, but not to the expression of HSP 27. No statistical significance was observed in histological types and gender with respect to both HSP 70 and HSP 27 expression. It is suggested that the HSP 70 expression is a powerful and significant prognostic indicator and is related to histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history, whereas HSP 27 expression is not.展开更多
BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological ...BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.展开更多
BACKGROUND： Heatstroke often leads to multiple organ dysfunction syndrome （MODS） with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the prog...BACKGROUND： Heatstroke often leads to multiple organ dysfunction syndrome （MODS） with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specifi c treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment.METHODS： A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrifi ced. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes.RESULTS： All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C.CONCLUSIONS： The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.展开更多
目的探讨清肺化痰汤治疗痰热郁肺证老年晚期非小细胞肺癌患者的临床疗效及对其生活质量、血清癌胚抗原(Carcinoembryonic antigen,CEA)、神经元特异性烯醇化酶(Neuron specific enolase,NSE)、细胞角质素片段抗原(Cytokeratin 19 fragme...目的探讨清肺化痰汤治疗痰热郁肺证老年晚期非小细胞肺癌患者的临床疗效及对其生活质量、血清癌胚抗原(Carcinoembryonic antigen,CEA)、神经元特异性烯醇化酶(Neuron specific enolase,NSE)、细胞角质素片段抗原(Cytokeratin 19 fragment antigen21-1,CYRAF21-1)水平的影响。方法选取2019年7月—2020年10月期间在东南大学医学院附属南京同仁医院接受治疗的非小细胞肺癌患者80例,采用随机数字表法分为对照组和观察组,每组各40例。对照组采用DP化疗方案治疗,观察组在对照组基础上联合清肺化痰汤治疗,每个疗程为21 d,连续治疗4个疗程。观察比较两组患者临床疗效、不良反应情况,治疗前后痰热郁肺证证候积分(咳嗽,咳痰、咯痰黄稠,气喘或气急,喉中痰鸣,发热,口渴)、血清肿瘤标记物(CEA、NSE、CYRAF21-1)、生命质量量表(QOL-38)评分改善情况。结果治疗后观察组总缓解率62.5%(25/40)、临床获益率85.0%(34/40)均明显高于对照组总缓解率40.0%(16/40)、临床获益率65.0%(26/40),差异有统计学意义(P<0.05)。治疗后两组患者咳嗽、咳痰、咯痰黄稠、气喘或气急、喉中痰鸣、发热、口渴评分均较治疗前降低,差异有统计学意义(P<0.01);且观察组痰热郁肺证证候积分明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清CEA、NSE及CYRAF21-1水平均较治疗前明显降低,差异有统计学意义(P<0.01);且观察组血清CEA、NSE及CYRAF21-1水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者身体状况、情绪状况、功能状况、肺癌相关症状、社会/家庭状况评分均较治疗前明显降低,总体健康状况评分较治疗前明显升高,差异有统计学意义(P<0.01);且观察组QOL-38评分改善情况明显优于对照组,差异有统计学意义(P<0.05)。治疗期间,观察组不良反应发生率明显低于对照组,差异有统计学意义(P<0.05)。结论清肺化痰汤治疗痰热郁肺证老年晚期非小细胞肺癌疗效显著,能够有效降低血清CEA、NSE及CYRAF21-1水平,缓解临床症状,减轻化疗药物不良反应,提高患者生活质量。展开更多
【目的】评价加味普济消毒颗粒(由金银花、连翘、蒲公英、紫花地丁、荆芥、牛蒡子、皂角刺、赤芍、牡丹皮、芦根等组成)内服联合消肿散结膏(由黄芩、黄连、黄柏、皂角刺等组成)外敷治疗儿童急性扁桃体炎(acute tonsillitis in children,...【目的】评价加味普济消毒颗粒(由金银花、连翘、蒲公英、紫花地丁、荆芥、牛蒡子、皂角刺、赤芍、牡丹皮、芦根等组成)内服联合消肿散结膏(由黄芩、黄连、黄柏、皂角刺等组成)外敷治疗儿童急性扁桃体炎(acute tonsillitis in children,ATC)的临床疗效及对免疫功能与相关炎症指标的影响。【方法】将116例ATC肺胃郁热证患儿随机分为对照组和观察组,每组各58例。对照组给予头孢克肟分散片治疗,观察组给予加味普济消毒颗粒内服联合消肿散结膏外敷治疗,疗程为14 d并随访6个月。观察2组患儿治疗前后中医证候积分、外周血中白细胞计数(WBC)、T淋巴细胞亚群CD3^(+)、CD4^(+)、CD8^(+)和CD4^(+)/CD8^(+)水平及血清肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、C反应蛋白(CRP)水平的变化情况,比较2组患儿的临床疗效和各项临床症状消失时间,同时监测2组患儿的不良反应发生情况和扁桃体炎复发情况。【结果】(1)研究期间,对照组有8例患儿脱落,观察组无脱落病例,最终对照组50例、观察组58例患儿完成全部疗程的治疗。(2)治疗14 d后,观察组的总有效率为98.28%(57/58),对照组为90.00%(45/50);组间比较(秩和检验),观察组的临床疗效明显优于对照组(P<0.05)。(3)治疗后,观察组患儿的咽痛消失时间、脓点消失时间、退热时间及扁桃体恢复正常时间均较对照组明显缩短(P<0.05)。(4)治疗后,2组患儿的主症积分、次症积分和中医证候总积分均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05)。(5)治疗后,2组患儿的T淋巴细胞亚群CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)水平均较治疗前明显升高(P<0.05),CD8^(+)水平均较治疗前明显降低(P<0.05),且观察组对T淋巴细胞亚群CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)水平的升高幅度及对CD8^(+)水平的降低幅度均明显优于对照组(P<0.05)。(6)治疗后,2组患儿的WBC、TNF-α、IL-1β、IL-6及CRP水平均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05)。(7)治疗期间,2组患儿均未出现皮肤过敏及恶心、呕吐等胃肠道不良反应情况,具有较高的安全性。(8)随访6个月,观察组患儿的扁桃体炎复发率为5.17%(3/58),明显低于对照组的24.00%(12/50),组间比较,差异有统计学意义(χ2=8.330,P<0.05)。【结论】加味普济消毒颗粒内服联合消肿散结膏外敷治疗ATC肺胃郁热证患儿疗效显著,可明显缩短病程,改善临床症状,有效降低扁桃体炎复发率,其机制可能与增强机体免疫功能、抑制炎症反应有关。展开更多
文摘BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.
文摘The heat shock proteins （HSPs） 70 and HSP 27 expression in patients with non-small cell lung cancer （NSCLC） was studied and the relation.ship between HSP 70 and HSP 27 with the clinicopathological features of NSCLC was investigated. The expression of HSP 70 and HSP 27 was detected in tumor tissues from 60 patients with NSCLC by S-P immunohistochemistry. The findings were analyzed in combination with the histological types, histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history and gender. The results showed that of the 60 NSCLC tissue specimens studied, the immunoreactivity of HSP 70 and HSP 27 was detected in 47 （78.3 %） and 43 （71.7 %） specimens, respectively. A positive correlation was found between the overexpression of HSP 70 and HSP 27. The histopathological differentiation, lymph node metastasis, clinical stages and smoking history were correlated to the expression of HSP 70, but not to the expression of HSP 27. No statistical significance was observed in histological types and gender with respect to both HSP 70 and HSP 27 expression. It is suggested that the HSP 70 expression is a powerful and significant prognostic indicator and is related to histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history, whereas HSP 27 expression is not.
文摘BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.
文摘BACKGROUND： Heatstroke often leads to multiple organ dysfunction syndrome （MODS） with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specifi c treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment.METHODS： A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrifi ced. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes.RESULTS： All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C.CONCLUSIONS： The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.
文摘目的探讨清肺化痰汤治疗痰热郁肺证老年晚期非小细胞肺癌患者的临床疗效及对其生活质量、血清癌胚抗原(Carcinoembryonic antigen,CEA)、神经元特异性烯醇化酶(Neuron specific enolase,NSE)、细胞角质素片段抗原(Cytokeratin 19 fragment antigen21-1,CYRAF21-1)水平的影响。方法选取2019年7月—2020年10月期间在东南大学医学院附属南京同仁医院接受治疗的非小细胞肺癌患者80例,采用随机数字表法分为对照组和观察组,每组各40例。对照组采用DP化疗方案治疗,观察组在对照组基础上联合清肺化痰汤治疗,每个疗程为21 d,连续治疗4个疗程。观察比较两组患者临床疗效、不良反应情况,治疗前后痰热郁肺证证候积分(咳嗽,咳痰、咯痰黄稠,气喘或气急,喉中痰鸣,发热,口渴)、血清肿瘤标记物(CEA、NSE、CYRAF21-1)、生命质量量表(QOL-38)评分改善情况。结果治疗后观察组总缓解率62.5%(25/40)、临床获益率85.0%(34/40)均明显高于对照组总缓解率40.0%(16/40)、临床获益率65.0%(26/40),差异有统计学意义(P<0.05)。治疗后两组患者咳嗽、咳痰、咯痰黄稠、气喘或气急、喉中痰鸣、发热、口渴评分均较治疗前降低,差异有统计学意义(P<0.01);且观察组痰热郁肺证证候积分明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清CEA、NSE及CYRAF21-1水平均较治疗前明显降低,差异有统计学意义(P<0.01);且观察组血清CEA、NSE及CYRAF21-1水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者身体状况、情绪状况、功能状况、肺癌相关症状、社会/家庭状况评分均较治疗前明显降低,总体健康状况评分较治疗前明显升高,差异有统计学意义(P<0.01);且观察组QOL-38评分改善情况明显优于对照组,差异有统计学意义(P<0.05)。治疗期间,观察组不良反应发生率明显低于对照组,差异有统计学意义(P<0.05)。结论清肺化痰汤治疗痰热郁肺证老年晚期非小细胞肺癌疗效显著,能够有效降低血清CEA、NSE及CYRAF21-1水平,缓解临床症状,减轻化疗药物不良反应,提高患者生活质量。
