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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

Journal of traditional Chinese medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI Qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang GUO Yi GUO Yongming research center of Experimental Acupuncture Science Tianjin University of Traditional Chinese Medicine National clinical research center for Chinese medicine Acupuncture and Moxibustion Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital) School of traditional Chinese medicine Tianjin University of Traditional Chinese Medicine School of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese Medicine

OBJECTIVE: To investigate the mechanisms behind the effects of acupuncture in traditional Chinese medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3) receptor signaling system as an indicator of the body's energy state,commonly referred to as "Qi".METHODS: The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice, while also assessing adenosine(ADO) levels and adenylate energy charge(EC) at Zusanli(ST36). The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects, the study examined the impact of ATP, a P2X3 receptor antagonist, and adenosine disodium on PTT following acupuncture administration. RESULTS: Acupuncture at Zusanli(ST36) led to significant improvements in PTT in mice, with the most effective interventions being twirling for 2 min and needle retention for 28 min. These interventions also resulted in significant increases in ATP levels. The effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36), and pretreatment with a P2X3 receptor antagonist decreased PTT. Adenylate EC peaked at 30 min after intraperitoneal injection of ATP, and pretreatment with various doses of i.p. ATP 30 min prior to acupuncture increased PTT in a dose-dependent manner. Additionally, pretreatment with an i.p. or intramuscular injection of adenosine disodium enhanced the effects of acupuncture. CONCLUSION: This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture, revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture adenosine triphosphate energy state point ST36 (Zusanli) receptors, purinergic P2X3

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Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian(BL54) through Shuidao(ST28) acupuncture

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Journal of traditional Chinese medicine 2024年第4期44卷 722-733页

作者： YAN Jing FENG Huimin QIU Fang WANG Haijun YIN Luyun JIN Xiaofei ZHAO Jiyu WANG Hongyang YAN Xiaoqin Second clinical College of Shanxi University of traditional Chinese medicine research center of Experimental Acupuncture Science Tianjin University of Traditional Chinese Medicine Department of Cervical and Lumbar Vertebral Diseases Jinzhong Hospital Affiliated to Shanxi University of Traditional Chinese Medicine

OBJECTIVE: To analyze the serum metabolic targets of the "Zhibian(BL54) through Shuidao(ST28)" acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. METHODS: We used an intraperitoneal injection of CTX to establish the POI rat model(POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54) through Shuidao(ST28) technique(ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS). RESULTS: After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. CONCLUSIONS: The "Zhibian(BL54) through Shuidao(ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.

关键词： Zhibian (BL54) through Shuidao (ST28) acupuncture metabolomics premature ovarian insufficiency ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

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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

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Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao Li Xiaoqian Shan Xi Chen Xuhe Yan Jianwei Liu Lan Zhao First Teaching Hospital of Tianjin University of traditional Chinese medicine TianjinChina National clinical research center for Chinese medicine Acupuncture and Moxibustion TianjinChina Tianjin University of traditional Chinese medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

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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 ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** 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 *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/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 *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** 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

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Tongqiao Yizhi granule(通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats

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Journal of traditional Chinese medicine 2024年第4期44卷 680-687页

作者： LI Yanjiao HAO Linyao LI Shuangyang LUO Yanqi WANG Juan WANG Raoqiong BAI Xue College of Integrative medicine Southwest Medical University Department of Neurology and National traditional Chinese medicine clinical research Base the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Institute of Integrated Chinese and Western medicine Southwest Medical University

OBJECTIVE: To explore the mechanism by which Tongqiao Yizhi granule（通窍益智颗粒, TQYZKL） intervenes pyroptosis to treat vascular dementia（VaD） in a rat model. METHODS: The rat model of VaD was established by two-vessel occlusion（2VO）. The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL（6.2 g·kg-1·d-1）, TQYZKL(12.4 g·kg-1·d-1), TQYZKL(24.8 g·kg-1·d-1). The Morris water maze（MWM） test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy（TEM） to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65（P65）, nucleotide oligomerization domain-like receptors 3（NLRP3）, caspase-1 and Gasdermin D（GSDMD）, were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β（IL-1β） and interleukin-18（IL-18） were determined through the enzyme-linked immunosorbent assay. RESULTS: The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β（P < 0.05）. CONCLUSION: TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

关键词： NF-kappa B NLR family, pyrin domain-containing 3 protein Tongqiao Yizhi granule caspase 1 dementia, vascular pyroptosis

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Efficacy and safety of electroacupuncture for insomnia:A systematic review and meta-analysis

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Journal of Integrative medicine 2024年第4期22卷 459-472页

作者： Han-yu Xu Lin-na Wu Yuan Zhang Te Ba Xiao-feng Zhao Acupuncture and Moxibustion Department First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China National clinical research center for Chinese medicine Acupuncture and Moxibustion Tianjin 300193China

Background:Electroacupuncture is often used to treat ***:To evaluate the efficacy and safety of electroacupuncture for *** strategy:Databases including PubMed,Cochrane Library,Embase,Web of Science,Chinese Biomedical Literature Database,China National Knowledge Infrastructure,Wanfang Data and VIP Fulltext e-Journals Database were searched up to January 15,*** criteria:Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture,no treatment or usual care (UC) and general *** extraction and analysis:The full texts of the studies were reviewed to remove ineligible *** extracted data included authors,publication year,diagnostic criteria,sample size,population characteristics,interventions and *** above steps were performed independently by two reviewers and the data were cross ***15.0 software was used to analyze the extracted outcome *** continuous data (Pittsburgh Sleep Quality Index[PSQI]score and Insomnia Severity Index score),weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was *** dichotomous variables (clinical response rate and adverse events),a meta-analysis was performed using risk ratio (RR) as the effect ***:Thirty-one trials with 2226 subjects were *** meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture,no treatment,UC and general acupuncture)(RR=1.21;95 CI:[1.16,1.27]),significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD=-3.23;95%CI:[-4.29,-2.17];P<0.001).There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or ***=1.48;95%CI:[0.91,2.40];P=0.117).In addition,the regression results revealed t

关键词： Electroacupuncture Insomnia Systematic review Meta-analysis

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Pathological progression of osteoarthritis:a perspective on subchondral bone

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Frontiers of medicine 2024年第2期18卷 237-257页

作者： Xuefei Li Wenhua Chen Dan Liu Pinghua Chen Shiyun Wang Fangfang Li Qian Chen Shunyi Lv Fangyu Li Chen Chen Suxia Guo Weina Yuan Pan Li Zhijun Hu Longhua Hospital Affiliated to Shanghai University of traditional Chinese medicine Shanghai200032China research and Development center of Chinese medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai201203China

Osteoarthritis(OA)is a degenerative bone disease associated with *** rising global aging population has led to a surge in OA cases,thereby imposing a significant socioeconomic *** have been keenly investigating the mechanisms underlying *** studies have suggested that the disease starts with synovial inflammation and hyperplasia,advancing toward cartilage ***,subchondral-bone collapse,sclerosis,and osteophyte formation *** progression is deemed as“top to bottom.”However,recent research is challenging this perspective by indicating that initial changes occur in subchondral bone,precipitating cartilage *** this review,we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state,functions,and the varied pathological shifts during OA *** also introduce the role of multifunctional signal pathways(including osteoprotegerin(OPG)/receptor activator of nuclear factor-kappa B ligand(RANKL)/receptor activator of nuclear factor-kappa B(RANK),and chemokine(CXC motif)ligand 12(CXCL12)/CXC motif chemokine receptor 4(CXCR4))in the pathology of subchondral bone and their role in the“bottom-up”progression of *** vivid pattern maps and clinical images,this review highlights the crucial role of subchondral bone in driving OA progression,illuminating its interplay with the condition.

关键词： osteoarthritis subchondral bone OPG/RANKL/RANK CXCL12/CXCR4

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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 ***,especially lower limb paralysis,often leads to the loss of self-care ability and a series of secondary *** main method to improve hemiplegic limb movement is exercise therapy,but there are still many patients with disabilities after rehabilitation *** one of the non-pharmacological therapies for stroke,acupuncture has been recognized to improve motor function in ***,we propose a new method,anterior sciatic nerve acupuncture,which can stimulate both the femoral nerve and the sciatic *** designed this study to determine the effect of this method on lower limb motor *** participants recruited with hemiplegia after cerebral infarction will be randomly assigned to the test group or control group in a 1:1 *** control group will receive Xingnao Kaiqiao acupuncture,and the test group will receive anterior sciatic nerve acupuncture on this *** participants will get acupuncture treatment once a day,6 times a week for 2 *** primary outcome is Fugl-Meyer Assessment of Lower Extremity and the secondary outcomes are Modified Ashworth Scale and Modified Barthel *** will be collected before treatment,1week after treatment,and 2 weeks after treatment,and then statistical analysis will be *** 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

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YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 525-541页

作者： Hua Sui Wanli Deng Qiong Chai Bing Han Yuli Zhang Zhenzhen Wei Zan Li Ting Wang Jiling Feng Man Yuan Qingfeng Tang Hongxi Xu Medical Experiment center Jiading Branch of Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201803China Translational medicine research center for Cancer Prevention and Treatment Shanghai General Hospital Jiading Branch-School of Pharmacy of Shanghai University of Traditional Chinese Medicine Joint LaboratoryShanghai201803China Department of Medical Oncology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai201203China The Second clinical Medical College of Henan University of traditional Chinese medicine Zhengzhou450000China Shanghai University of traditional Chinese medicine Shanghai201203China Precision research center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai201620China

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon *** previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling ***,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is *** this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling ***,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a ***,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)***,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)***,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 ***,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in ***,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within

关键词： Tumor microenvironment Intestinal epithelial cells Treg/Th17 cells Metabolism Wnt5a/JNK signaling Tumorigenesis

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