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Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes

Cancer Biology & Medicine 2020年第1期17卷 60-75页

作者： Bingtao Zhai Qibiao Wu Wengang Wang Mingming Zhang Xuemeng Han Qiujie li Peng Chen xiaying Chen Xingxing Huang Guohua li Qin Zhang Ruonan Zhang Yu Xiang Shuiping liu Ting Duan Jianshu Lou Tian Xie Xinbing Sui College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Holistic Integrative Pharmacy Institutes and Comprehensive Cancer Diagnosis and Treatment Center the Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhou 310018China State Key Laboratory of Quality Research in Chinese Medicines Faculty of Chinese MedicineMacao University of Science and TechnologyMacao 519020China Key Laboratory of Elemene Class Anticancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province Hangzhou Normal UniversityHangzhou 310018China

Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-lipo-β-E.Compared to elemene injection,PEG-lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(Plipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.

关键词： β-elemene PEGylated liposome pharmacokinetics antitumor effect bladder cancer

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父母教养方式与大学生课堂参与:学习动机的链式中介效应

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中国健康心理学杂志 2022年第11期30卷 1703-1709页

作者：郝夏盈李宪印曲阜师范大学教育学院 273165 曲阜师范大学中国教育大数据研究院

目的:基于自我决定理论,从积极心理学视角探究父母教养方式与大学生课堂参与的关系,以及内部动机、外部动机的链式中介作用。方法:采用父母教养方式问卷、学习动机问卷、课堂参与问卷对637名在读本科生进行施测,运用SPSS 25.0对父母教... 详细信息

目的:基于自我决定理论,从积极心理学视角探究父母教养方式与大学生课堂参与的关系,以及内部动机、外部动机的链式中介作用。方法:采用父母教养方式问卷、学习动机问卷、课堂参与问卷对637名在读本科生进行施测,运用SPSS 25.0对父母教养方式与大学生课堂参与水平之间的影响进行了实证分析,并使用PROCESS宏程序对外部学习动机与内部学习动机的中介作用进行了检验。结果:(1)在控制性别、年级等变量的前提下,仅有情感温暖型教养方式与外部动机、内部动机(r=0.341,0.342;P<0.01)、课堂参与(r=0.342,P<0.01)两两相关;(2)情感温暖经由3条中介路径对课堂参与产生正向预测作用:外部动机的独立中介作用,内部动机的独立中介作用,外部动机与内部动机的链式中介作用。结论:情感温暖型教养方式对课堂参与具有积极促进作用,也经由学习动机影响课堂参与水平,且两种动机类型存在链式中介作用。因此父母要注重家庭教育方式,提倡积极教养方式,多给予孩子温暖与鼓励,激发学生学习动机,调动学生课堂参与的积极性。

关键词：父母教养方式课堂参与学习动机链式中介效应

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An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

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Cancer Biology & Medicine 2020年第3期17卷 676-692页

作者： Bingtao Zhai Peng Chen Wengang Wang Shuiping liu Jiao Feng Ting Duan Yu Xiang Ruonan Zhang Mingming Zhang Xuemeng Han xiaying Chen Qiujie li Guohua li Ying liu Xingxing Huang Wenzheng Zhang Ting Pan lili Yan Ting Jin Tian Xie Xinbing Sui Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhou 310018China Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Provinee and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province Hangzhou Normal UniversityHangzhou 310018China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang UniversityHangzhou 310016China

Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-lipo-β-E).DDP,combined with ATF24-PEG-lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.

关键词： uPAR β-elemene active targeting liposome bladder cancer DDP

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PCDH17 increases the sensitivity of colorectal cancer to 5-fluorouracil treatment by inducing apoptosis and autophagic cell death

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Signal Transduction and Targeted Therapy 2019年第1期4卷 176-185页

作者： Shuiping liu Haoming lin Da Wang Qiang li Hong Luo Guoxiong li Xiaohui Chen Yongqiang li Peng Chen Bingtao Zhai Wengang Wang Ruonan Zhang Bi Chen Mingming Zhang Xuemeng Han Qiujie li liuxi Chen Ying liu xiaying Chen Guohua li Yu Xiang Ting Duan Jiao Feng Jianshu Lou Xingxing Huang Qin Zhang Ting Pan lili Yan Ting Jin Wenzheng Zhang Lvjia Zhuo Yitian Sun Tian Xie Xinbing Sui Holistic Integrative Pharmacy Institutes and Comprehensive Cancer Diagnosis and Treatment Center the Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhouZhejiangChina Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province Hangzhou Normal UniversityHangzhouZhejiangChina Department of Hepatobiliary Pancreatic Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Department of Colorectal Surgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Ultrasound Medicine The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang UniversityHangzhouChina Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingChina

5-Fluorouracil(5-FU)is known as a first-line chemotherapeutic agent against colorectal cancer(CRC),but drug resistance occurs frequently and significantly limits its clinical success.Our previous study showed that the protocadherin 17(PCDH17)gene was frequently methylated and functioned as a tumor suppressor in CRC.However,the relationship between PCDH17 and 5-FU resistance in CRC remains unclear.Here,we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues,and high expression of PCDH17 was correlated with high BECN1 expression.Moreover,this expression profile contributed to superior prognosis and increased survival in CRC patients.Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death.Furthermore,autophagy played a dominant role in PCDH17-induced cell death,as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK.PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity.Mechanistically,we showed that c-Jun NH2-terminal kinase(JNK)activation was a key determinant in PCDH17-induced autophagy.The compound SP600125,an inhibitor of JNK,suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells.Taken together,our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death.PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients.

关键词： death treatment apoptosis

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Erianin,a novel dibenzyl compound in Dendrobium extract,inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1882-1892页

作者： Peng Chen Qibiao Wu Jiao Feng lili Yan Yitian Sun Shuiping liu Yu Xiang Mingming Zhang Ting Pan xiaying Chen Ting Duan lijuan Zhai Bingtao Zhai Wengang Wang Ruonan Zhang Bi Chen Xuemeng Han Yicong li liuxi Chen Ying liu Xingxing Huang Ting Jin Wenzheng Zhang Hong Luo Xiaohui Chen Yongqiang li Qiujie li Guohua li Qin Zhang Lvjia Zhuo Zuyi Yang Huifen Tang Tian Xie Xiaoping Ouyang Xinbing Sui Holistic Integrative Pharmacy Institutes and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhouZhejiangChina Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghai 201203China Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province Hangzhou Normal UniversityHangzhouZhejiangChina State Key Laboratory of Quality Research in Chinese Medicines Faculty of Chinese MedicineMacao University of Science and TechnologyMacaoP.R.China Zhejiang Chinese Medicinal University HangzhouChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina Department of Medical Oncology Zhejiang UniversityHangzhouChina Department of Hematology and Oncology the Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhouZhejiangChina Radiation Detection Research Center Northwest Institute of Nuclear TechnologyXi’anChina Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingChina

Ferroptosis,a novel form of programmed cell death,is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases,including cancer.Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy.Therefore,ferroptosis-inducing drugs are attracting more attention for cancer treatment.Here,we showed that erianin,a natural product isolated from Dendrobium chrysotoxum lindl,exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells.Subsequently,we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells,which was accompanied by ROS accumulation,lipid peroxidation,and GSH depletion.The ferroptosis inhibitors Fer-1 and lip-1 but not Z-VAD-FMK,CQ,or necrostatin-1 rescued erianin-induced cell death,indicating that ferroptosis contributed to erianin-induced cell death.Furthermore,we demonstrated that Ca^(2+)/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis.Taken together,our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca^(2+)/CaMdependent ferroptosis and inhibiting cell migration,and erianin will hopefully serve as a prospective compound for lung cancer treatment.

关键词： peroxidation lung drugs

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血清NSE尿VMA水平联合血细胞分析评估神经母细胞瘤患儿预后的价值分析

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河北医学 2023年第11期29卷 1826-1832页

作者：沈夏赢金鑫李树锦安徽省合肥市第二人民医院检验科安徽合肥230011

目的:分析神经元特异性烯醇化酶(Neuron-Specific Enolase,NSE)、尿香草苦杏仁酸(vanillylmandelic acid,VMA)水平联合血细胞分析评估神经母细胞瘤患儿预后情况。方法:选取2018年1月至2021年3月来我院治疗的101例神经母细胞瘤患儿,根据... 详细信息

目的:分析神经元特异性烯醇化酶(Neuron-Specific Enolase,NSE)、尿香草苦杏仁酸(vanillylmandelic acid,VMA)水平联合血细胞分析评估神经母细胞瘤患儿预后情况。方法:选取2018年1月至2021年3月来我院治疗的101例神经母细胞瘤患儿,根据随访2年预后结局将患者分为存活组和死亡组,存活组69例,死亡组32例。比较两组患儿一般临床资料、实验室指标水平、血小板、红细胞情况,比较不同临床分期患儿实验室指标水平。结果:两组患儿一般临床资料比较:两组患者年龄、性别、首发部位、病理类型、平均血小板体积进行比较,无差异(P>0.05),存活组患儿Ⅲ~Ⅳ期、N-myc基因阳性、高危、骨髓转移比例、NSE、血清铁蛋白(Serum Ferritin,SF)、乳酸脱氢酶(Lactate Dehydrogenase,LDH)、C反应蛋白(C-reactive protein,CRP)、24h尿VMA水平、血小板分布宽度以及红细胞分布宽度低于死亡组,差异有统计学意义(P<0.05),Ⅰ~Ⅱ期患儿NSE、SF、LDH、CRP、24h尿VMA水平显著低于Ⅲ~Ⅳ期患儿,差异有统计学意义(P<0.05),存活组血小板压积高于死亡组,差异有统计学意义(P<0.05),Logistic回归分析,结果表明:分期、NSE、24h尿VMA、血小板分布宽度是神经母细胞瘤患儿预后的影响因素(P<0.05),NSE(ng/mL)、血小板分布宽度(%)、24h尿VMA测定值(μmoL/L),预测神经母细胞瘤患儿预后的ROC曲线下面积AUC值分别为0.862(0.791~0.932)、0.838(0.743~0.934)、0.748(0.641~0.856),截断值分别为45.565、10.375、51.405,灵敏度分别为0.823、0.781、0.711,特异度分别为0.841、0.790、0.681,约登指数分别为0.664、0.571、0.392。结论:神经母细胞瘤患儿VMA、NSE、血小板分布宽度与预后结局有关,各指标联合预测神经母细胞瘤患儿预后有较好的应用价值。

关键词：血清神经元特异性烯醇化酶尿香草苦杏仁酸血细胞神经母细胞瘤血小板分布宽度

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Integration of chemical and biological methods:A case study of polycyclic aromatic hydrocarbons pollution monitoring in Shandong Peninsula,China

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Journal of Environmental Sciences 2022年第1期34卷 24-37页

作者： Zeyuan li Yunhao Cao Huawei Qin Yuanqing Ma Luqing Pan Jiawei Sun Key Laboratory of Mariculture Ministry of EducationOcean University of ChinaQingdao 266003China Shandong Marine Resources and Environment Research Institute Yantai 264006China

Polycyclic aromatic hydrocarbons(PAHs),as persistent toxic substances(PTS),have been widely monitored in coastal environment,including seawater and sediment.However,scientific monitoring methods,like ecological risk assessment and integrated biomarker response,still need massive researches to verify their availabilities.This study was performed in March,May,August and October of 2018 at eight sites,Yellow River estuary(S1),Guangli Port(S2),xiaying(S3),Laizhou(S4),Inner Bay(S5),Outer Bay(S6),Hongdao(S7)and Hongshiya(S8)of Shandong Peninsula,China.The contents of 16 priority PAHs in local seawater and sediment were determined,by which ecological risk assessment risk quotient(RQ)for seawater and sediment quality guidelines(SQGs)were calculated to characterize the PAHs pollution.Meanwhile,multiple biomarkers in the digestive gland of clam Ruditapes philippinarum were measured to represent different biological endpoints,including ethoxyresorufin-O-deethylase(EROD),glutathione S-transferase(GST),sulfotransferase(SULT),superoxide dismutase(SOD)and lipid peroxidation(LPO),by which integrated biomarker response(IBR)was calculated to provide a comprehensive assessment of environmental quality.Taken together,these results revealed the heaviest pollution at S2 as both PAHs concentrations and biomarkers responses reflected,and supported the integrated biomarker response as a useful tool for marine environmental monitoring,through its integration with SQGs.

关键词： Shandong Peninsula Polycyclic aromatic hydrocarbons(PAHs) Ruditapes philippinarum Risk quotient Sediment quality guidelines Integrated biomarker response

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六一散联合可视性鼻贴在普外科病人鼻部管道固定中的应用

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护理研究 2022年第4期36卷 744-746页

作者：章丽姣李秀萍孙于舒赵夏英潘红英浙江大学医学院附属邵逸夫医院浙江310016

目的:探讨六一散联合可视性鼻贴在普外科病人鼻部管道固定中的应用效果。方法:选取2020年1月—2020年12月在浙江省某医院普外科住院并留置鼻部管道的病人209例,随机分为3组,A组(69例)采用3M敷贴制成的"工"字形鼻贴固定,B组(70例)采用3M... 详细信息

目的:探讨六一散联合可视性鼻贴在普外科病人鼻部管道固定中的应用效果。方法:选取2020年1月—2020年12月在浙江省某医院普外科住院并留置鼻部管道的病人209例,随机分为3组,A组(69例)采用3M敷贴制成的"工"字形鼻贴固定,B组(70例)采用3M敷贴制成的可视性鼻贴固定,C组(70例)在B组的基础上联合六一散固定,比较3组病人鼻贴更换时间、鼻部皮肤不良反应(痒、红、破损)以及非计划拔管的发生率。结果:3组鼻部皮肤不良反应发生率、鼻贴更换时间及非计划拔管发生率比较差异均有统计学意义(P<0.05)。结论:六一散联合可视性鼻贴固定鼻部导管有助于延长鼻贴更换时间,降低鼻部皮肤不良反应及非计划拔管率。

关键词：六一散可视性鼻贴胃管营养管非计划拔管护理

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氮沉降模拟实验亟待研究大气氨浓度增加的影响

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Atmospheric and Oceanic Science Letters 2020年第3期13卷 248-251页

作者： PAN Yuepeng TIAN Shili WU Dianming XU Wen ZHU xiaying liU Chunyan li Dejun FANG Yunting DUAN Lei liU Xuejun WANG Yuesi State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry(LAPC) Institute of Atmospheric PhysicsChinese Academy of SciencesBeijingChina Key Laboratory of Geographic Information Sciences Ministry of EducationSchool of Geographic SciencesEast China Normal UniversityShanghaiChina College of Resources and Environmental Sciences China Agricultural UniversityBeijingChina National Climate Center China Meteorological AdministrationBeijingChina Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangshaHunanChina CAS Key Laboratory of Forest Ecology and Management Institute of Applied EcologyChinese Academy of SciencesShenyangLiaoningChina State Key Laboratory of Environmental Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijingChina

大气活性氮污染及其过量沉降是全球变化重要议题。为研究氮沉降对自然生态系统结构和功能的影响,基于喷淋加氮的控制实验在草地或林下广泛开展。该实验体系假定氮沉降是通过增加土壤氮的有效性从而影响整个生态系统,没有考虑植被与大气... 详细信息

大气活性氮污染及其过量沉降是全球变化重要议题。为研究氮沉降对自然生态系统结构和功能的影响,基于喷淋加氮的控制实验在草地或林下广泛开展。该实验体系假定氮沉降是通过增加土壤氮的有效性从而影响整个生态系统,没有考虑植被与大气活性氮的相互作用,也未能反映氮沉降以干沉降为主的自然过程。考虑到大气氨是氮沉降的主要前体物,且全球氨气浓度呈现上升趋势,未来的氮沉降模拟实验亟待研究氨气干沉降的重要影响,以期更加完整的刻画大气氮沉降过程及其生态环境效应。

关键词：氮沉降湿沉降干沉降氨气大气污染

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2012年冬春季高原积雪异常对亚洲夏季风的影响

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气象 2013年第9期39卷 1111-1118页

作者：竺夏英陈丽娟李想国家气候中心中国气象局气候研究开放实验室北京100081

利用罗格斯大学积雪遥感资料、NCEP/NCAR再分析格点资料和NOAA陆地降水分析数据PREC/L,从2011/2012年冬春季青藏高原积雪偏多现象与亚洲夏季风的观测事实与以往研究结果不一致出发,诊断分析了2011/2012年冬春积雪与亚洲夏季风的可能联... 详细信息

利用罗格斯大学积雪遥感资料、NCEP/NCAR再分析格点资料和NOAA陆地降水分析数据PREC/L,从2011/2012年冬春季青藏高原积雪偏多现象与亚洲夏季风的观测事实与以往研究结果不一致出发,诊断分析了2011/2012年冬春积雪与亚洲夏季风的可能联系。结果表明:2012年春季和前期冬季,青藏高原主体上空对流层主要为气旋性环流距平且气温偏低,这与积雪偏多年的环流特征一致。尤其在90°E以西,自青藏高原到热带地区,前期冬春季对流层中部气温表现为北冷南暖的距平特征,有利于夏季自热带印度洋到高原温度梯度偏弱,造成南亚夏季风偏弱。但是在90°E以东的高原东部到东亚地区及其南侧的低纬度地区,对流层温度距平为北正南负型,温度梯度偏弱,有利于亚洲东南部大气环流冬夏季节转换偏早,南海夏季风爆发偏早,东亚夏季风偏强,这种环流特征受到高原以外的其他外强迫信息的影响。2011/2012年冬春季积雪偏多特征可能对南亚夏季风偏弱有重要贡献,而对东亚夏季风的影响不明显。

关键词：青藏高原积雪温度梯度亚洲夏季风

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