OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cispla...OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.展开更多
目的:探讨神经性厌食患者的人格特征及焦虑抑郁症状,为临床治疗和疾病预防提供参考依据。方法:选取94例同时符合中国精神障碍分类与诊断标准第3版(CCMD-3)和美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的神经性厌食患者,其中限食...目的:探讨神经性厌食患者的人格特征及焦虑抑郁症状,为临床治疗和疾病预防提供参考依据。方法:选取94例同时符合中国精神障碍分类与诊断标准第3版(CCMD-3)和美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的神经性厌食患者,其中限食型41例,暴食/清除型53例;选取72例某精神专科医院实习护士为对照组。两组均采用明尼苏达多项人格(MMPI)、汉密顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)进行测查。结果:病例组抑郁症状(85.1%vs.8.3%)和焦虑症状(75.5%vs.2.8%)的检出率高于对照组(均P<0.05)。病例组M M PI测试结果除男子-女子气、说谎量表、诈病量表、校正量表的T分与对照组无统计学差异外(均P>0.05),精神病态、抑郁、癔病、疑病、偏执、精神衰弱、精神分裂症、轻躁狂及社会内向的T分均高于对照组(均P<0.05);T分最高的量表分为精神病态(Pd)(63.8±11.2),其次是抑郁(D)(61.0±12.8),两点编码呈现24/42编码。暴食/清除型患者的疑病(Hs)的T分高于限食型[(53.3±9.9)vs.(58.7±9.3),P<0.05]。结论:神经性厌食患者有其特定的人格特征,尤其是精神病态和抑郁更为突出。展开更多
基金National Natural Science Foundation of China(82174143)and Scientific Research Foundation of Guangdong Pharmaceutical University(51348136)。
文摘OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.
文摘目的:探讨神经性厌食患者的人格特征及焦虑抑郁症状,为临床治疗和疾病预防提供参考依据。方法:选取94例同时符合中国精神障碍分类与诊断标准第3版(CCMD-3)和美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的神经性厌食患者,其中限食型41例,暴食/清除型53例;选取72例某精神专科医院实习护士为对照组。两组均采用明尼苏达多项人格(MMPI)、汉密顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)进行测查。结果:病例组抑郁症状(85.1%vs.8.3%)和焦虑症状(75.5%vs.2.8%)的检出率高于对照组(均P<0.05)。病例组M M PI测试结果除男子-女子气、说谎量表、诈病量表、校正量表的T分与对照组无统计学差异外(均P>0.05),精神病态、抑郁、癔病、疑病、偏执、精神衰弱、精神分裂症、轻躁狂及社会内向的T分均高于对照组(均P<0.05);T分最高的量表分为精神病态(Pd)(63.8±11.2),其次是抑郁(D)(61.0±12.8),两点编码呈现24/42编码。暴食/清除型患者的疑病(Hs)的T分高于限食型[(53.3±9.9)vs.(58.7±9.3),P<0.05]。结论:神经性厌食患者有其特定的人格特征,尤其是精神病态和抑郁更为突出。
