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Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone IIA@ Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

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Energy & Environmental Materials 2024年第2期7卷 191-203页

作者： Ling Yu Yubin Liang Lei Gao Peipei Chen Zhiqiang Yu Minzhou Zhang Aleksander Hinek Shuai Mao Second clinical college Guangzhou University of Chinese Medicine Department of Critical Care medicine Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Branch of National clinical Research Centre for Chinese medicine Cardiology Department of Radiation medicine and Applied Sciences University of California San Diego Department of Laboratory medicine Dongguan Institute of Clinical Cancer Research Affiliated Dongguan Hospital Southern Medical University Translational medicine Hospital for Sick Children

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid) gel(PLGA-PEG-PLGA) system encapsulating tanshinone IIA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen speciestriggered release properties in a high-reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local antipyroptotic and anti-inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone ***, this novel, precision-guided intra-tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

关键词： myocardial infarction ROS-sensitive polymer tanshinone IIA thermoreversible hydrogel ventricular remodeling

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Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 136-152页

作者： Xiaoju Guo Xiaoxiao Chen Jiayi Ding Feng Zhang Shunyang Chen Xin Hu Shiji Fang Lin Shen Chenying Lu Zhongwei Zhao Jianfei Tu Gaofeng Shu Minjiang Chen Jiansong Ji Lishui Central Hospital Shaoxing UniversityShaoxing 312000China Zhejiang Key Laboratory of Imaging and Interventional medicine Imaging Diagnosis and Interventional Minimally Invasive InstituteThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China clinical college of The Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000China Key Laboratory of Precision medicine of Lishui Lishui 323000China

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

关键词： CaCO3-based nanoparticles Hypoxia attenuation Acidity neutralization Reversal of chemotherapy resistance Enhanced chemo-immunotherapy

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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 ***: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 ***:Sixteen RCTs with a cumulative sample size of 1178 cases were *** these,964 patients were included in 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),P<0.01].AM was better than the control group in improving the visual analog scale scores[standard mean difference(SMD)=0.62,95%CI(0.53,0.71),P<0.01].AM was superior to the control group in improving Numerical Rating Scale(NRS)symptom scores[OR=7.31,95%CI(3.36,15.94),P<0.01].There was no significant difference in adverse effects between the AM and sham-AM groups 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 ***:AM is more effective than other treatments or pharmacotherapy alone in the treatment of pregnancy-related symptoms,and is relatively ***,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

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No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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Chinese Journal of Integrative medicine 2024年第2期30卷 99-106页

作者： SU Tao FANG Zhi-e GUO Yu-ming WANG Chun-yu WANG Jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal Division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney Diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December ***-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of *** primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to ***:A total of 337 patients diagnosed with AAN were included in this *** the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with *** cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary ***:No cases of liver cancer were observed at the end of ***,a high prevalence of urinary cancer was observed in AAN *** a direct causality between AA and HCC is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

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Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

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Chinese Journal of Natural medicines 2024年第3期22卷 224-234页

作者： WU Yuanyuan ZHOU Jingwen ZUO Xinchen KUANG Yufeng SUN Lixia ZHANG Xiaolong The First clinical Medical college Nanjing University of Chinese MedicineNanjing 210023China The Affiliated Hospital of Nanjing University of Chinese medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as *** Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely *** study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological *** simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were *** severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine *** results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid ***,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and ***,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo *** preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.

关键词： Non-alcoholic steatohepatitis Nuclear factor kappa B NLRP3 inflammasome Yanggan Jiangmei Formula

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Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

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Chinese Medical Journal 2024年第12期137卷 1453-1464页

作者： Xia Qiu Hedong Zhang Zhouqi Tang Yuxi Fan Wenjia Yuan Chen Feng Chao Chen Pengcheng Cui Yan Cui Zhongquan Qi Tengfang Li Yuexing Zhu Liming Xie Fenghua Peng Tuo Deng Xin Jiang Longkai Peng Helong Dai Medical college Guangxi UniversityNanningGuangxi 530004China Department of Kidney Transplantation Center of Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China National clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Organ Transplantation The Fifth Clinical Medical College of Henan University of Chinese Medicine(Zhengzhou People’s Hospital)ZhengzhouHenan 450000China

Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied ***,we explored the therapeutic effects of HHT in a mouse heart transplant ***:Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver,kidney,and hematology.A mouse heart transplantation model was constructed,and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan-Meier analysis,immunostaining,and bulk RNA sequencing *** HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells(Tregs)***:HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex *** of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days(P<0.001)without non-immune *** allografts had long-term survival after continuous HHT treatment for 28 *** significantly reduced lymphocyte infiltration in the graft,and interferon-γ-secreting CD4^(+)and CD8^(+)T cells in the spleen(P<0.01).HHT significantly increased the number of peripheral Tregs(about 20%,P<0.001)and serum interleukin(IL)-10 *** downregulated the expression of T cell receptor(TCR)signaling pathway-related genes(CD4,H2-Eb1,TRAT1,and CD74)and upregulated the expression of IL-10 and transforming growth factor(TGF)-βpathway-related genes and Treg signature genes(CTLA4,Foxp3,CD74,and ICOS).HHT increased CD4^(+)Foxp3^(+)cells and Foxp3 expression ex vivo,and it enhanced the inhibitory function of inducible ***:HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels,thereby promoting mouse heart allograft *** findings may have therapeutic implications for organ tr

关键词： Heart transplantation Homoharringtonine Immunosuppressive agents T-lymphocytes,Regulatory Graft acceptance

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Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

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Journal of Pharmaceutical Analysis 2024年第6期14卷 889-901页

作者： Shaowei Huang Xueqian Xie Bo Xu Zengfeng Pan Junjie Liang Meiling Zhang Simin Pan Xiaojing Wang Meng Zhao Qing Wang Jinyan Chen Yanyang Li Lian Zhou Xia Luo School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine510006China School of Basic medicine Guangzhou University of Chinese Medicine510006China First clinical Medical college Guangzhou University of Chinese Medicine510000China

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains *** this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG *** detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,***,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for *** results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal ***,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune *** additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via *** conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

关键词： Paeoniflorin Ulcerative colitis Intestinal mucosal barrier DR3 signaling pathway Group 3 innate lymphoid cells

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Pathological mechanisms of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第5期19卷 1036-1044页

作者： Yushu Hu Wenzhi Chen Caihui Wei Shishi Jiang Shu Li Xinxin Wang Renshi Xu Department of clinical medicine Nanchang UniversityNanchangJiangxi ProvinceChina Department of Neurology Jiangxi Provincial People’s HospitalNanchangJiangxi ProvinceChina Department of Neurology The First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of ***,the journey to understanding or treating amyotrophic lateral sclerosis is still a long *** to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic *** progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral ***,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral *** addition,we discuss current emerging strategies for the treatment of amyotrophic lateral *** the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

关键词： amyotrophic lateral sclerosis cellular pathways disease mechanisms motor neuron neurodegenerative disease

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A prognostic model of patients with pancreatic cancer based on four N^(6)-methyladenosine-related IncRNAs and analysis of related immune infiltration

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Genes & Diseases 2024年第4期11卷 109-112页

作者： Kaili Liao Yuhan Xu Bingying Lin Yuxuan Xie Qijun Yang Wenyige Zhang Beining Zhang Jiarong Wen Jingyi Wang Zimeng Li Yunqi Cheng Xiaozhong Wang Jiangxi Province Key Laboratory of Laboratory medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Queen Mary college of Nanchang University NanchangJiangxi 330001China School of Public Health Nanchang UniversityNanchangJiangxi 330006China The Second clinical Medical college Nanchang UniversityNanchangJiangxi 330006China The First clinical Medical college of Nanchang University NanchangJiangxi 330006China

Pancreatic cancer is one of the most lethal malignant tumors in the *** advances in diagnosis and treatment,the five-year survival rate for pancreatic cancer patients remains only 9%.1 Pancreatic adenocarcinoma(PAAD)belongs to pancreatic cancer,which occupies 85%of the whole pancreatic cancer.2 Reversible modification of Ne-methyladenosine(m^(6)A)has been shown to be involved in cancer progression,resulting in up-regulation of oncogene expression or down-regulation of tumor-suppressing genes and may affect the prognosis of patients with pancreatic cancer.

关键词： patients cancer diagnosis

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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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