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chinese Journal of Integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China Shandong Co-innovation Center of Classic traditional chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver disease.Polysaccharides extracted from chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and anti-oxidation.The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment.In addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota.This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

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chinese Journal of Natural medicines 2024年第1期22卷 62-74页

作者： GUO Qiru LI Jiali WANG Zheng WU Xiao JIN Zhong ZHU Song LI Hongfei ZHANG Delai HU Wangming XU Huan YANG Lan SHI Liangqin WANG Yong College of Basic medicine Chengdu University of Traditional Chinese MedicineChengdu 610000China Chengdu University of traditional chinese medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610000China

Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular remodeling.Potassium dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections.This study investigates the potential of PDA in regulating pathological vascular remodeling.The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice.Experimental approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions.The results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima formation.PDA treatment significantly increased the proliferation and migration of SMCs.Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular remodeling.Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

关键词： Potassium dehydroandrographolide succinate Smooth muscle cell Myeloid differentiation factor 88 T-cadherin Pathological vascular remodeling

Effectiveness and safety of acupuncture in treatment of pregnancyrelated symptoms:a systematic review and Meta-analysis

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Journal of traditional chinese medicine 2024年第1期44卷 16-26页

作者： LIU Tingting LIU Tongou LIU Mingfu School of traditional chinese medicine Clinical medicine Hubei University of Traditional Chinese MedicineWuhan 430000China First Clinical College of Hubei University of traditional chinese medicine Wuhan 430000China Department of Acupuncture and Tuina Affiliated Hospital of Hubei University of Traditional Chinese MedicineHubei Provincial Hospital of Traditional Chinese MedicineWuhan 430000China

OBJECTIVE:To systematically evaluate the efficacy and safety of acupuncture(AM)in the treatment of pregnancyrelated symptoms such as acute vomiting during pregnancy.METHODS:We comprehensively searched the available literature up to November 2021,including Pub Med,Embase,Cochrane Library,chinese Biomedical Literature Database,and China National Knowledge Infrastructure Database,for randomized controlled trials(RCTs)on AM for the treatment of severe vomiting,insomnia,pharyngeal and pelvic pain,mood abnormalities,and dyspepsia during pregnancy.RESULTS:Sixteen RCTs with a cumulative sample size of 1178 cases were included.Of these,964 patients were included in the Meta-analysis.The Meta-analysis results showed that AM was more efficient than Western medicine in treating discomfort during pregnancy[odds ratio(OR)=1.19,95%confidence interval(CI)(1.11,1.28),Pgroup in improving the visual analog scale scores[standard mean difference(SMD)=0.62,95%CI(0.53,0.71),Pgroup in improving Numerical Rating Scale(NRS)symptom scores[OR=7.31,95%CI(3.36,15.94),Pgroups and the analgesic drug group[OR=0.70,95%CI(0.39,1.28),P=0.25],but the treatment and control groups had mild adverse effects with a low incidence.CONCLUSIONS:AM is more effective than other treatments or pharmacotherapy alone in the treatment of pregnancy-related symptoms,and is relatively safe.However,the quality of the included trials was rather poor,and high-quality studies are required to confirm our findings.

关键词： acupuncture pregnancy nausea vomiting sleep initiation and maintenance disorders low back pain pelvic pain mood abnormalities Meta-analysis systematic review

Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, molecular Dynamics Simulation and Experimental Validation

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chinese Journal of Integrative medicine 2024年第5期30卷 408-420页

作者： FENG Min-chao LUO Fang HUANG Liang-jiang LI Kai CHEN Zu-min LI Hui YAO Chun QIN Bai-jun CHEN Guo-zhong The First Clinical Medical College Guangxi University of Traditional Chinese MedicineNanning 530000China Guangxi Key Laboratory of molecular Biology of traditional chinese medicine and Preventive medicine Nanning 530000China Graduate School Guangxi University of Traditional Chinese MedicineNanning 530000China Department of Gastroenterology the First Affiliated Hospital of Guangxi University of Traditional Chinese MedicineNanning 530023China

Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.

关键词： Rheum palmatum L. Salvia miltiorrhiza Bge. molecular docking simulation network pharmacology acute pancreatitis Th17 cell differentiation

Efficacyand Safetyof Huashi Baidu Granules in Treating Patients with SARS-CoV-2Omicron Variant: A Single-Center Retrospective Cohort Study

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chinese Journal of Integrative medicine 2024年第2期30卷 107-114页

作者： CHEN Cai-yu ZHANG Wen XU Xiang-ru PU Yu-ting TU Ya-dan PENG Wei YAO Xuan ZHOU Shuang FANG Bang-jiang Department of Emergency Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai(200032)China Department of Classical traditional chinese medicine Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Acupuncture and Massage College Shanghai University of Traditional Chinese MedicineShanghai(201203)China Institute of Emergency and Critical Care medicine Shanghai University of Traditional Chinese MedicineShanghai(200032)China

Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,2022.All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users.Patients in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive days.Patients in the control group received standard care and routine treatment.The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7.Secondary outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic patients.Adverse events(AEs)that occurred during the study were recorded.Further subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);Pgroup were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);Pgroups[3 days(IQR:2-4 days)vs.5 days(IQR:4-6 days);P<0.01].The incidence of new-onset sym

关键词： Huashi Baidu Granule severe acute respiratory syndrome coronavirus 2 Omicron variant retrospective cohort trial chinese medicine

molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping Xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng Tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern research Center for traditional chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern research Center for traditional chinese medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply.However,the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated.This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa.It displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides.Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides.Additionally,it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions.QM/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation regiospecificity.Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for glucosides.Furthermore,a mutant CtMaT1H36A with notably increased di-malonylation activity was obtained.The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation.This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension:A randomized,double-blind,placebo-controlled trial

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Journal of Integrative medicine 2024年第4期22卷 484-492页

作者： Jun Xie Yu-long Ma Ming-tai Guia Lei Yao Jian-hua Li Ming-zhu Wang Xun-jie Zhou Yi-fan Wang Ming-yi Zhao Hui Cao Bo Lu De-yu Fu Department of Cardiology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine Shanghai University of traditional chinese medicine

Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated traditional chinese and Western medicine,Shanghai University of traditional chinese medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmH

关键词： chinese herbal compound Glycolipid metabolism Huoxue Qianyang Qutan Recipe Hypertension Inflammatory Target organ damage

Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

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Journal of traditional chinese medicine 2024年第3期44卷 448-457页

作者： ZHANG Zeyu JIA Zhuangzhuang SONG Yuwei ZHANG Xuan WANG Ci WANG Shuai ZHANG Peipei REN Qiuan WANG Xianliang MAO Jingyuan Department of Cardiovascular the First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

关键词： extracellular regulated protein kinases heart failure mitogen-activated protein kinases myocardial fibrosis optimized new Shengmai powder rapidly accelerated fibrosarcoma sarcoma

Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7

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chinese Journal of Integrative medicine 2024年第6期30卷 543-550页

作者： YU Qian SHU Shi JU Xin-yao PENG Wei REN Xue-qi SI Shu-han SONG Shi-zhen XIE Xue-yun FANG Bang-jiang ZHOU Shuang School of Acupuncture-Moxibustion and Tuina Shanghai University of Traditional Chinese MedicineShanghai201203China College of Basic medicine Shanghai University of Traditional Chinese MedicineShanghai201203China Department of Emergency Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai200032China

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(KLF4/VEGF)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(Pgroup(Pgroup(P<0.01).After miR-7 knockdown,the expression of KLF4/VEGF 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 KLF4/VEGF and ANG-2.

关键词： electroacupuncture cerebral ischemia miRNA-7 angiogenesis Shuigou(GV 26) acupuncture points

Effects of anterior sciatic nerve acupuncture on lower limb paralysis after cerebral infarction:study protocol for a randomized controlled trial

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Journal of traditional chinese medicine 2024年第1期44卷 205-211页

作者： LI Menghan WANG Yu RAN Dawei YANG Xinming DENG Shizhe SHI Lei MENG Zhihong Department of Acupuncture First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China National Clinical research Center for chinese medicine Acupuncture and Moxibustion Tianjin 300193China Graduate department Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Massage and Rehabilitation Second Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300250China

Stroke is the main cause of disability in the middle and old age.Hemiplegia,especially lower limb paralysis,often leads to the loss of self-care ability and a series of secondary injuries.The main method to improve hemiplegic limb movement is exercise therapy,but there are still many patients with disabilities after rehabilitation treatment.As one of the non-pharmacological therapies for stroke,acupuncture has been recognized to improve motor function in patients.Here,we propose a new method,anterior sciatic nerve acupuncture,which can stimulate both the femoral nerve and the sciatic nerve.We designed this study to determine the effect of this method on lower limb motor function.Sixty participants recruited with hemiplegia after cerebral infarction will be randomly assigned to the test group or control group in a 1:1 ratio.The control group will receive Xingnao Kaiqiao acupuncture,and the test group will receive anterior sciatic nerve acupuncture on this basis.All participants will get acupuncture treatment once a day,6 times a week for 2 weeks.The primary outcome is Fugl-Meyer Assessment of Lower Extremity and the secondary outcomes are Modified Ashworth Scale and Modified Barthel Index.Data will be collected before treatment,1week after treatment,and 2 weeks after treatment,and then statistical analysis will be performed.This study can preliminarily verify the effect of anterior sciatic nerve acupuncture on improving lower limb motor function in patients with cerebral infarction,which may provide an alternative approach for clinical treatment of hemiplegia.

关键词： anterior sciatic nerve acupuncture paralysis cerebral infarction Xingnao Kaiqiao clinical protocols