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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The vip Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of vip Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of vip Medical center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of Liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic ***(HLP)is the leading risk factor for *** study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were *** plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver ***,KAL levels of NAFLD patients were significantly *** transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)*** contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD ***,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),***-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa ***,hepatic CGl-58-overexpress reverses NASH in KAL transgenic ***,free fatty acids up-regulated KAL against thyroid hormone in ***,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating *** results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying Wen Xixiang Tang Zheyao Wen Rui Zhang Shasha Li Rong Gao Jin Wang Yanhua Zhu Dong Fang Ting Li Ruiping Peng Zhaotian Zhang Shiyi Wen Li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen Department of Endocrinology and Metabolic Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China vip Medical Service center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(DR)remains *** retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR *** single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 RAs STING signaling Retinal endothelial cells Mitochondrial leakage Retinal vascular dysfunction Diabetic retinopathy CREB Inflammation

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Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

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World Journal of Pediatrics 2024年第3期20卷 259-271页

作者： Yi-Long Wang Meng-Ying Zhu Zhe-Feng Yuan Xiao-Yan Ren Xiao-Tong Guo Yi Hua Lu Xu Cong-Ying Zhao Li-Hua Jiang Xin Zhang Guo-Xia Sheng Pei-Fang Jiang Zheng-Yan Zhao Feng Gao Department of Neurology Children's HospitalZhejiang University School of MedicineHangzhou 310052China Children's Hospital Zhejiang University School of MedicineHangzhou 310052China Children's Hospital National Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhou 310052China

Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous *** Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative *** partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics *** analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and *** enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with *** Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(vip)scores>*** proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA vip lists were *** analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC *** The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

关键词： Acute disseminated encephalomyelitis Cerebrospinal fluid Complement cascades Myelin oligodendrocyte glycoprotein-associated disease Proteomics

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Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Controlled Trials

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Chinese Journal of Integrative Medicine 2024年第3期30卷 260-266页

作者： XIU Wen-cui GANG Wei-juan ZHOU Qi SHI Lan-jun HU Xiang-yu MING Tian-yu LUO Zhen ZHANG Yu-qing JING Xiang-hong Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing100700China China center for Evidence-Based Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijing100700China Department of health Research Methods Evidenceand ImpactMcMaster UniversityHamiltonOntarioL8S 4L8Canada center for Evidence-Based Integrative Medicine-Clarity Collaboration Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China

Background:The effects of acupuncture have varied in different randomized controlled trials(RCTs),and there are many factors that influence treatment effect of acupuncture in different outcomes,with conflicting ***:To identify factors and their impact on the treatment effect of acupuncture in different ***:Acupuncture RCTs were searched from 7 databases including Medline(Pub Med),Embase,Cochrane Central Register of Controlled Trials,China National Knowledge Infrastructure,Wanfang Database,vip Database,and China Biology Medicine disc between January 1st,2015 and December 31st,*** studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting lists,and report at least 1patient-important outcome.A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables,even those excluded from the multivariable model due to *** used thresholds of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as small(0.4) ***:The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent ***-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude,the difference of adjusted SMDs 0.46,95% confidence interval(CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent *** acupuncture showed moderately larger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct analysis included 495 effect estimates from 274 studies and 14 independent *** acupuncture and the flexible acupuncture regimen showed moderately larger effects,compared to non-penetrating acupuncture and fixed regimen,respectively(0.40,95% CI 0

关键词： acupuncture randomized controlled trial patient-important outcome meta-regression

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Cardiac involvement in light chain amyloidosis: a case report

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Journal of Geriatric Cardiology 2020年第6期17卷 373-378页

作者： Jing LI Hong-Yan WANG Ning BIAN Ru-Yi XU Can HUA Shao-Li NIU Zhuo-Kun GAN Qing WANG Hai-Tao TIAN vip Cardiovascular Department the Sixth Medical Center of Chinese PLA General Hospital

Amyloidosis refers to a group of heterogeneous diseases in which amyloid fibers deposited in organ and extracellular tissue comprise misfolded precursor proteins.[1] According to the variety of misfolded proteins, the site of production and the type of tissue infiltrated, amyloidosis of the myocardium is divided into five subtypes: immunoglobulin light chain(AL), secondary amyloidosis(or reactive amyloido-

关键词： Arrhythmias Cardiac amyloidosis Diagnosis Immunoglobulin light chains Thromboembolism

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Short-term outcomes of albumin-bound paclitaxel (abraxane)-containing chemotherapy in patients with advanced gastric cancer: a report of 14 cases

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The Chinese-German Journal of Clinical Oncology 2013年第1期12卷 30-34页

作者： Zheng Yan Liangping Xia Huijuan Qiu Ping Chen Bei Zhang vip Region Sun Yat-sen University Cancer Center

Objective： Albumin-bound paclitaxel （abraxane, ABX） has more favorable efficacy and less toxicity than conventional taxanes. However, the data of ABX in advanced gastric cancer （AGC） treatment is unavailable. The current study was designed to summarize our experience in treating AGC patients with ABX. Methods： The clinical data of patients with AGC who had received at least one cycle of ABX-based chemotherapy in Sun Yat-sen University Cancer center from January 10th 2010 to May 14th 2012 was retrospectively analyzed. Results： A total of 47 cycles of ABX-containing regimens, with a median of 3 cycles （range： 1-8 cycles）, were administered to 14 patients. Five （35.7%） partial responses and 6 （42.9%） stable diseases were obtained, with a disease control rate （DCR） of 78.6%. The median progression free survival （PFS） and overall survival （OS） were 3.3 and 10.8 months, respectively. Interestingly, patients in the first-line setting achieved a DCR of 100% （8/8）. Neutropenia and thrombocytopenia were the main grade 3/4 adverse events with an incidence of 50% in the whole group. However, only 25% patients （2/8） experienced grade 3 neutropenia when ABX in combination with fluoropyrJmJdines. Conclusion： The activity of ABX-based regimens as first-line therapy for patients with AGC is remarkable, and the toxicity is mild when ABX combined with fluorepyrimidines. Further prospective clinical trials of ABX-based chemotherapy as first-line treatment for AGC are strongly anticipated.

关键词： albumin-bound paclitaxel (abraxane, ABX) gastric cancer efficacy toxicity chemotherapy

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Palliative primary tumor resection provides survival beneits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen

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Chinese Journal of Cancer 2016年第9期35卷 468-475页

作者： Wen-Zhuo He Yu-Ming Rong Chang Jiang Fang-Xin Liao Chen-Xi Yin Gui-Fang Guo Hui-Juan Qiu Bei Zhang Liang-Ping Xia State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat?sen University Cancer Center vip Region Sun Yat?sen University Cancer Center

Background: It remains controversial whether palliative primary tumor resection(PPTR) can provide survival benefits to the patients with metastatic colorectal cancer(m CRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with m ***: We conducted a retrospective study on consecutive m CRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival(OS) and progression?free survival(PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient ***: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months(P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months(P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group(219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group(95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase(LDH) levels and with carcinoembryonic antigen(CEA) levels <70 ng/m L benefited from PPTR(median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001).Conclusions: For m CRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/m L.

关键词：乳酸脱氢酶结直肠癌转移性患者肿瘤水福利手术切除

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Research of Brucea javanica against Cancer

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Chinese Journal of Integrative Medicine 2017年第2期23卷 153-160页

作者： YAN Zheng GUO Gui-fang ZHANG Bei State Key Laboratory of Oncology in South China Guangzhou510060China vip Region Sun Yat-sen University Cancer CenterGuangzhou510060China Collaborative Innovation center for Cancer Medicine Guangzhou510060China

Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarize... 详细信息

关键词： Brucea javanica cancer Chinese herbal medicine apoptosis

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