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中国结合医学杂志（英文版）
中国结合医学杂志（英文版）

陈可冀

月刊

1672-0415

cjim@cjim.cn,

010-62877592

100091

北京西苑操场1号

中国结合医学杂志（英文版）/Journal Chinese Journal of Integrative MedicineCSCDCSTPCD北大核心SCI
查看更多>>本刊主要宣传党的中医政策和中西医结合方针，报道我国中西医结合在临床、科研、预防、教学等方面的经验和成果，探讨中西医结合的思路和方法，介绍国内外有关本专业的进展，开展学术讨论，为提高西医结合水平、继承和发扬我国传统的医药学、促进我国医学科学现代化服务。
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    Challenges and Opportunities in the Practice of Chinese Medicine in Singapore

    CHEW Sin Yee
    483-488页
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    Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer:Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

    CAO Ni-daZHU Xiao-hongMA Fang-qiXU Yan...
    489-498页
    查看更多>>摘要：Objective:To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC patients.Methods:This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,2021.Overall survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment ≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for bias.Results:A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled.Among them,1,607 received systemic chemotherapy,215(10.74％)accepted molecular targeted therapy,44(2.2％)received checkpoint inhibitor therapy,and 769(38.43％)received CM.Two-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09％).While 45.71％(16 cases)of patients with HER2 amplification received trastuzumab in first-line.The application of apatinib increased(33.33％)in third-line.The application of checkpoint inhibitors has increased since 2020.COX analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment＞6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of AGC.After PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P＜0.001).Conclusions:In real-world practice for AGC in China,therapy choices consisted with guidelines.Two-drug regimen was the main first-line choice.Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC.(Registration No.NCT02781285)
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    Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly inhibiting E3 Ubiquitin Ligase

    LI QiKONG Zhao-diWANG HuanGU Hong-hui...
    499-506页
    查看更多>>摘要：Objective:To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction(JP)and to explore its mechanism of anti-cancer cachexia.Methods:A mouse model of colon cancer(CT26)-induced cancer cachexia(CC)was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate(MPA).Thirty-six mice were equally divided into 6 groups:normal control,CC,MPA(100 mg·kg-1·d-1),MPA+low-dose(20 mg·kg-1·d-1)JP(L-JP),MPA+medium-dose(30 mg·kg-1·d-1)JP(M-JP),and MPA+high-dose(40 mg·kg-1·d-1)JP(H-JP)groups.After successful modeling,the mice were administered by gavage for 11 d.The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation.The liver,heart,spleen,lung,kidney,tumor and gastrocnemius muscle of mice were collected and weighed.The pathological changes of the tumor was observed,and the cross-sectional area of the gastrocnemius muscle was calculated.The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot.In addition,an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy.In vitro experiments were divided into control,model,and JP serum groups.After 2-d administration,microscopic photographs were taken and myotube diameters were calculated.Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase.Results:JP combined with MPA restored tumor-induced weight loss(P＜0.05,vs.CC)and muscle fiber size(P＜0.01,vs.CC).Mechanistically,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo(P＜0.05,vs.CC).In addition,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(P＜0.05 or P＜0.01 vs.model group)in C2C12 myotubes treated with dexamethasone in vitro.Conclusions:Administration of JP combined with MPA restores tumor-induced cachexia conditions.In addition,the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis(E3 ubiquitinase system).
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    Mechanism Exploration of Euphorbia fischeriana Steud.for Liver Cancer Based on Aspartic Acid Identification in Metabolomics

    ZHAO JingTIAN Xin-chenZHANG Jia-qiHUANG Chen...
    507-514页
    查看更多>>摘要：Objective:To investigate the anti-liver cancer effects and aspartic acid(Asp)-related action mechanism of Euphorbia fischeriana Steud.(LD).Methods:The mice model of liver cancer was established by injection of H22 cells.After 5 days,mice were randomly divided into model group,sorafenib group(20 mg/kg),LD high-dose(LDH,1.36 g/kg)group,LD medium-dose(LDM,0.68 g/kg)group,and LD low-dose(LDL,0.34 g/kg)group,10 mice each group.Drugs were intragastrically administered to the mice once daily for 10 days,respectively.Body weight,tumor size and tumor weight were recorded.Hepatic index was calculated.Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining.Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups.Results:After LD treatment,tumor weight,tumor size and hepatic index were reduced compared with the model group.Necrocytosis and karyorrhexis of tumor cells were found.Moreover,61 differential metabolites(18 up-regulated,43 down-regulated)were affirmed and 20 pathways of KEGG(P＜0.05)were gotten.In addition,Bel-7402,HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium.And then,the cell proliferation effect induced by Asp was ameliorated by LD.Conclusion:The anti-liver cancer efficacy of LD extract was validated in H22 mice model,and inhibition of Asp level might be the underlying mechanism.
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    Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

    CAO Liu-jingLIU Li-yaCHEN You-qinHAN Yu-ying...
    515-524页
    查看更多>>摘要：Objective:To explore the regulatory effect of Pien Tze Huang(PZH)on targeting partner of NOB1(PNO1)and it's down-stream mediators in colorectal cancer(CRC)cells.Methods:Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1,TP53,and CDKN1A.Western blotting was performed to determine protein levels of PNO1,p53,and p21.HCT-8 cells were transduced with a lentivirus over-expressing PNO1.Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment.Cell-cycle distribution,cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment.Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated.Western blot assay was performed to detect PNO1,p53,p21 and PCNA expression in tumor sections.Terminal deoxynucleotidyl transferase dUTP nick end labling(TUNEL)assay was used to determine the apoptotic cells in tissues.Results:PZH treatment decreased cell viability,down-regulated PNO1 expression,and up-regulated p53 and p21 expressions in HCT-8 cells(P＜0.05).PNO1 overexpression attenuated the effects of PZH treatment,including the expression of p53 and p21,cell growth,cell viability,cell cycle arrest and cell apoptosis in vitro(P＜0.05).PNO1 knockdown eliminated the effects of PZH treatment on tumor growth,inhibiting cell proliferation inhibition and apoptosis induction in vivo(P＜0.05).Similarly,PNO1 knockdown attenuated the effects of PZH treatment on the downregulation of PNO1 and up regulation of p53 and p21 in vivo(P＜0.05).Conclusion:The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.
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    Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+Signaling

    Lucas dos Santos ZamarioliMichele Rosana Maia SantosAdolfo Garcia ErustesVanessa Marques Meccatti...
    525-533页
    查看更多>>摘要：Objective:To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods:Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results:HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P＜0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P＜0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P＜0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P＜0.01).HEAV-induced Ca2+release mainly from lysosomes in K562 cells(P＜0.01).Furthermore,BAPTA-AM,an intracellular Ca2+chelator,decreased the number of non-viable cells treated with HEAV(P＜0.05).Conclusions:HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca2+.These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.
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    Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

    LI JieCHEN Ya-fengGAO LeiLI Yi-jie...
    534-542页
    查看更多>>摘要：Objective:To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods:Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results:Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P＜0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P＜0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1,however,HON treatment increased the nuclear level of HMGB1(P＜0.01).HON treatment also inhibited the expressions of JAK1,JAK2,and STAT1(P＜0.01)and increased the acetylation of HMGB1(P＜0.05).Conclusion:HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.
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    Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7

    YU QianSHU ShiJU Xin-yaoPENG Wei...
    543-550页
    查看更多>>摘要：Objective:To observe the angiogenesis effect of electroacupuncture(EA)at Shuigou acupoint(GV 26)in the treatment of cerebral ischemia,and explore the value of miRNA-7(miR-7)in it.Methods:First,48 mice were randomly divided into sham operation,middle cerebral artery occlusion(MCAO)model,and EA treatment groups.Then 9 mice were divided into carrier control group,miR-7 knockout group and miR-7 overexpression group(n=3 each group).Finally,20 mice were divided into model and carrier control group,model and miR-7 knockout group,EA treatment and carrier control group and EA treatment and miR-7 overexpression group,with 3-6 mice in each group.The MCAO model was established in the MCAO and EA groups.Neurological deficit score and 2,3,5-triphenyltetrazolium chloride(TTC)staining were used to evaluate the severity of cerebral ischemia.Hematoxylin-eosin staining was used to describe basic pathological changes.Immunohistochemistry was used to quantify cerebral microvessel density.Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor(KLF4NEGF)and angiopoietin-2(ANG-2)in the ischemic cerebral cortex.Results:After EA,neurological deficit scores and infarction volumes decreased,and the density of cerebral microvessels increased.In the MCAO group,miR-7 expression was higher than that in the sham group(P＜0.01).After EA at GV 26,miR-7 expression decreased(P＜0.01)and the expression of downstream target genes KLF4NEGF and ANG-2 increased as compared with the MCAO group(P＜0.01).After EA combined with overexpression of miR-7,the expression of downstream target genes KLF4NEGF and ANG-2 decreased compared to the control EA group(P＜0.01).After miR-7 knockdown,the expression of KLF4NEGF and ANG-2 increased(P＜0.05 or P＜0.01).Conclusions:EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4NEGF and ANG-2.
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    Use of Evidence-Based Research Approach in RCTs of Acupuncture-Related Therapies for Primary Dysmenorrhea:A Meta-Research

    HU Xiao-yiTIAN Zi-yuCHEN HuanHU Xiang-yu...
    551-558页
    查看更多>>摘要：Objective:To assess the use of evidence-based research(EBR)approach in randomized controlled trials(RCTs)of acupuncture-related therapies for primary dysmenorrhea(PD).Methods:PubMed,EMBASE,Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Biomedical Database,and China Science and Technology Journal Database were searched from January 2013 to December 2022 for RCTs of acupuncture on PD.The full text and references of each RCT were read to assess whether systematic reviews(SRs)or other types of studies with similar research questions and end-users'perspectives were cited to justify and design the trial.In addition,the discussion section were analyzed to evaluate whether trials placed the new result in the existing SRs to draw a conclusion.Multivariable logistic regression was used to find variables that associated with 3 aspects of EBR approach:(1)citing clinical studies for justification,(2)citing relevant studies that obtain the perspectives of end users,and(3)citing clinical studies for results discussion.Results:Of 473 RCTs included,45.67％(216)of the trials cited relevant similar studies,21.56％(102)referenced to the studies that collected end-users'perspectives,and 10.99％(52)placed result in the context of the previous research.Few RCTs appropriately applied EBR approach.Among all the included studies,3.17％(15)of the trials used SRs to inform study questions but none of them used updated SRs with acceptable quality;1.05％(5)of the trials cited SRs of end-user's perspectives in the justification and design of the study,and only 1 trial added results in existing SR to draw a conclusion.Year of publication,language,funding,registration,ethical approval and number of sites were significantly associated with 1 of the 3 aspects of EBR approach.Conclusions:Few RCTs in acupuncture-related therapies for PD used the EBR approach to minimize research redundancy.Researchers,research institutes,funding agencies,ethics committees,journals and peer reviewers in acupuncture should make efforts to use and promote the EBR approach to ensure the value of new trials.
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    Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

    ZHANG Rong-rongSHAO Ming-yiFU YuZHAO Rui-xia...
    559-564页
    查看更多>>摘要：Objective:To evaluate the benefit-risk of 3 commonly used Chinese medicine injections,Aidi Injection(ADI),Cinobufagin Injection(CINI)and Compound Kushen Injection(CKI),in the treatment of primary liver cancer(PLC),so as to provide a reference for clinical decision-making.Methods:Randomized controlled trials(RCTs)of ADI,CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure,Wanfang,China Science and Technology Journal Database,SinoMed,PubMed,Cochrane Library,and Web of Science were retrieved from January 2020 to October 2022.The data of benefit and risk indicators were combined to obtain the effect value.The multi-criteria decision analysis(MCDA)model was applied to build the decision tree.The benefit value,risk value and benefit risk value of the 3 injections in PLC treatment were calculated.Monte Carlo simulation was carried out to calculate the 95％confidence interval and probability of differences among the 3 injections,so as to optimize the evaluation results.Results:A total of 71 RCTs were included.The benefit values of ADI,CINI and CKI combined with transcatheter arterial chemoembolization(TACE)were 42,38 and 36,respectively.The risk values were 42,25 and 37,respectively.The benefit risk values were 42,31 and 37,respectively.The benefit risk differences of ADI vs.CINI,ADI vs.CKI,and CKI vs.CINI were 11(-0.86,17.75),5(-5.01,11.09),and 6(-1.87,12.63),respectively.The probability that ADI superior to CINI,ADI superior to CKI,and CKI superior to CINI was 96.26％,77.27％,and 92.62％,respectively.Conclusion:Based on the results of MCDA model,CINI combined with TACE has the greatest risk in the treatment of the PLC.Considering the efficacy and safety,the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI,CKI and CINI.
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