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Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 568-580页

作者： Hao ZHANG Xinshu WANG Bo HU Peicheng LI Yierfan ABUDUAINI Hongmei ZHAO Ayinaer JIEENSIHAN Xishuang CHEN Shiyu WANG Nuojin GUO Jian YUAN Yunhui LI Lei LI Yuntong YANG Zhongmin LIU Zhaosheng TANG Hua WANG Department of Endocrinology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Research Center for Translational medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Biochemistry and Molecular Biology School of MedicineTongji UniversityShanghai 200331China Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai East HospitalShanghai 200120China Ji’an hospital Shanghai East HospitalJi’an 343000China

diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA *** umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)***-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains *** this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with *** glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were *** that interacted with IGF1R were determined through coimmunoprecipitation *** expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot ***-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of *** identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red *** rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and ***1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown *** cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin *** infusion ameliorated abnormalities and preserved kidney structure and function in DM *** expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased sign

关键词： Insulin-like growth factor 1 receptor(IGF1R) Checkpoint kinase 2(CHK2) Protein 53(p53) Diabetes mellitus Human umbilical cord mesenchymal stem cell(HUcMSC) DNA damage repair

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Organic Integration of Traditional Chinese and Western medicines—Future of Clinical Practice Guidelines of Integrated Traditional Chinese and Western medicines

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Chinese Journal of Integrative medicine 2024年第4期30卷 359-365页

作者： XIE Ying-lan HAN Fei JIN Ying-hui DING Yan-bing GUO Jing JI Dong-xiao ZHANG Teng CHENXiao-min SHANG Hong-cai Department of Traditional Chinese medicine Encephalopathy Hubei Provincial Hospital of Traditional Chinese MedicineWuhan(430074)China Department of Traditional Chinese medicine Encephalopathy Hubei Province Traditional Chinese Medicine Research InstituteWuhan(430074)China Xuanwu hospital of Traditional Chinese medicine Beijing(100000)China Center for Evidence-Based and Translational medicine Zhongnan Hospital of Wuhan UniversityWuhan(430074)China College of Acupuncture and Massage College of Health and RehabilitationNanjing University of Chinese MedicineNanjing(210023)China Department of Ophthalmology Huaihe Hospital of Henan UniversityKaifengHenan Province(475000)China Ministry of Education and Beijing Key Laboratory of Internal medicine of Traditional Chinese medicine Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine/Ministry of Education and Beijing Key Laboratory of Internal Medicine of Traditional Chinese MedicineBeijing(100700)China

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine(TCM)and Western medicine(WM)is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the ***,clinical practice guidelines(CPGs)of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives:(1)perspective of TCM and WM integration in guidelines,(2)diagnosis Using integrated TCM and WM,(3)integration of TCM and WM treatment,(4)promoting TCM and WM ***,the information and quality evaluation of CPGs for integrated Chinese and Western medicine in 2020–2022 were analyzed to explore the degree and methods of integration of Chinese and Western medicine *** last this study aimed to lay a foundation for the further establishment of Chinese characteristic,repeatable,and calculable clinical practice guidelines of TCM and WM integration.

关键词： clinical practice guidelines integrated traditional Chinese and Western medicine organic integration

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Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer

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Journal of Integrative medicine 2024年第3期22卷 295-302页

作者： Zhengting Deng Shufang Liang Guokai Huang Yuqian Wang Xiaoyu Tu Yani Zhang Shu Li Tao Liu Binbin Cheng Taizhou hospital of Traditional Chinese medicine Nanjing University of Chinese MedicineTaizhou 225300Jiangsu ProvinceChina Oncology Department of Traditional Chinese medicine The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China School of Traditional Chinese medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Gastroenterology Baoshan Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 201900China

Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer ***: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron ***: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax ***, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell *** starvation increased autophagy and amplified the effect of As2O3on cell ***: As2O3induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights

关键词： Apoptosis Arsenic trioxide Autophagy Primary liver cancer

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Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

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Military Medical Research 2024年第3期11卷 313-322页

作者： Ying-Hui Jin Yan-Ping Wang Ying-Lan Xie Gui-Hua Tian Xiao-Yu Zhang Nan-Nan Shi Ke-Hu Yang Xin Sun Yao-Long Chen Da-Rong Wu Xin-Feng Guo Long Ge Chen Zhao Cheng Lu Yin Jiang Jing Guo Si-Yu Yan Yong-Bo Wang Qiao Huang Xiang-Ying Ren Ying-Yue Rao Yun-Yun Wang Meng-Qian Yuan Xian-Tao Zeng Hong-Cai Shang Center for Evidence-Based and Translational medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Institute of Basic Research in Clinical medicine China Academy of Chinese Medical SciencesBeijing 100700China China Center for Evidence Based Traditional Chinese medicine Beijing 100029China Hubei Provincial hospital of Traditional Chinese medicine Wuhan 430074China Key Laboratory of Chinese Internal medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Evidence-Based medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China China Center for Evidence-Based medicine West China Hospital of Sichuan UniversityChengdu 610041China State Key Laboratory of Dampness Syndrome of Chinese medicine the Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Evidence-based medicine Team Guangdong Provincial Hospital of Traditional Chinese MedicineGuangzhou 510120China Nanjing University of Chinese medicine Nanjing 210023China Jiangsu Province hospital of Chinese medicine Nanjing 210029China

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in *** TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and ***,the methodological defects in currently published clinical practice guidelines(CPGs)limit its *** organic integration of TCM and WM is a deeper integration of TCM and *** realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is ***,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

关键词： Methodology Traditional Chinese medicine Western medicine Organic integration Clinical practice guidelines(CPGs)

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Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

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Neural Regeneration Research 2024年第8期19卷 1655-1657页

作者： Sarah Buchholz Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine Cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological *** Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

关键词： Alzheimer Zimmer tau

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Effect and Safety of Herbal medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy:A Multicenter Double-Blind Randomized Controlled Trial

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Chinese Journal of Integrative medicine 2024年第3期30卷 195-202页

作者： HUANG Hao-yue LIN Yu-ping WEI Hua FU Yu ZHOU Yue-hong FANG Zhao-hui QIU Xiao-tang WANG Mei LI Qing-bo LI Shan-shan WANG Shi-dong DAI Fang LIU Zhen-jie ZHAO Ling WEN Jian-xuan WU Li-yan ZENG Hui-yan ZHANG Jin-ming LU Qi-yun HE Liu SONG Wei SUN Lu LUO Lu-lu HE Jia-li XIE Wen-wen LIANG Qing-shun HUANG Yuan ZHU Sheng-ling LONG Jie-er GAO Zhi-juan WEN Ze-huai LI Chun-ji OUYANG Wen-wei LI Geng WU Ming-hui LI An-xiang HUANG Jin-zhu Sanjoy K Paul TANG Xian-yu FAN Guan-jie Department of Endocrinology Guangdong Provincial Hospital of Chinese MedicineGuangzhou510120China The Second Clinical College of Guangzhou University of Chinese medicine Guangzhou510120China Department of Endocrinology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou510120China Department of Endocrinology The First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Department of Endocrinology Liuyang Hospital of Chinese MedicineChangsha410000China Department of Endocrinology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230000China Department of Endocrinology Hainan Provincial Hospital of Traditional Chinese MedicineHaikou570100China Department of Endocrinology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang110000China Department of Geriatric Luoyang No.1 Hospital of Traditional Chinese MedicineLuoyangHenan Province471000China Department of Endocrinology The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Department of Endocrinology Beijing University of Chinese Medicine Affiliated Dongzhimen HospitalBeijing100000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550000China Melbourne EpiCentre The University of Melbourne and Melbourne HealthMelbourne3013Australia

Objective:To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction(TW)in treating patients with diabetic peripheral neuropathy(DPN).Methods:It is a multicenter double-blinded randomized controlled *** with DPN were recruited between November 18,2016 and May 30,2018 from 8 hospitals in *** patients received basic treatments for glycemic *** received foot baths with TW herbal granules either 66.9 g(intervention group)or 6.69 g(control group)for 30 min once a day for 2 weeks and followed by a 2-week rest,as a therapeutic *** the Toronto Clinical Scoring System total score(TCSS-TS)6 points,the patients received a total of 3 therapeutic courses(for 12 weeks)and were followed up for 12 *** primary outcome was change in TCSS-TS score at 12 and 24 *** outcomes included changes in bilateral motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the median and common peroneal *** was also ***:Totally 632 patients were enrolled,and 317 and 315 were randomized to the intervention and control groups,*** the 12-week intervention,patients in both groups showed significant declines in TCSSTS scores,and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment(P0.05),and no serious adverse event was related with ***:Treatment of TW foot baths was safe and significantly benefitted patients with DPN.A low dose of TW appeared to be more effective than a high dose.(Registry *** CTR-IOR-16009331)

关键词： diabetic peripheral neuropathy herbal medicine foot baths Chinese medicine randomized controlled trial Tangbi Waixi Decoction

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang Department of Thoracic Surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Thoracic Surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina Department of Thoracic Surgery Changhai HospitalNaval Medical UniversityShanghaiChina Department of Thoracic-Cardiovascular Surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Department of Thoracic Surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： Surgery chemotherapy treatment

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International standard of Traditional Chinese medicine Techniques: Traditional Chinese medicine guidelines for acute primary headache(2022)

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Journal of Traditional Chinese medicine 2024年第4期44卷 839-850页

作者： YAO Yuning CAO Kegang ZHANG Genming LIU Jianping CHEN Wei CAO Junling YANG Wenming YAN Yongmei GENG Chang JU Yi ZHAO Dexi QU Miao LI Xiaoli SUN Li HAN Zhenyun HE Liyun CUI Fangyuan FU Caihong ZHOU Bo LIAO Shuqin Department of Geriatrics Jilin Academy of Traditional Chinese Medicine Department of Neurology Shenzhen Hospital of Beijing University of Chinese Medicine Institute of Basic Research in Clinical medicine China Academy Of Chinese Medical Sciences Department of Rehabilitation Shunyi HospitalBeijing Traditional Chinese Medicine Hospital Department of Neurology Xiyuan Hospital of China Academy of Chinese Medical Sciences Department of Neurology Dongzhimen Hospital of Beijing University of Chinese Medicine Centre for Evidence-Based Chinese medicine Beijing University of Chinese Medicine Encephalopathy center First Affiliated Hospital of Anhui University of Chinese Medicine Department of Neurology Affiliated Hospital of Shaanxi University of Chinese Medicine Department of Neurology Beijing Changping District Hospital of Traditional Chinese Medicine Neurology center Beijing Tiantan HospitalCapital Medical University Department of Neurology Affiliated Hospital of Changchun University of Chinese Medicine Department of Neurology Xuanwu HospitalCapital Medical University Department of Neurology Beijing University of Chinese Medicine Third Affiliated Hospital

OBJECTIVE: To summarize the evidence from Traditional Chinese medicine(TCM) practice in the treatment of acute primary headache and provide clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization guideline development manual. After the establishment of steering committee, panel and the registration and protocol formulation, the evidence on TCM for acute primary headache from published guidelines, clinical evidence, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended three TCM herbal decoctions, six Chinese patent medicines, and two kinds of external application of Chinese herbal medicines. Diagnostic recommendations based on the expert experience and consensus were also included in the guidelines. CONCLUSION: TCM diagnosis and treatment of decoction, Chinese patent medicine and external application for treating acute primary headache were recommended. We hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.

关键词： acute primary headache medicine, Chinese traditional practice guideline

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Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review

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Journal of Traditional Chinese medicine 2024年第3期44卷 609-619页

作者： WANG Yuhuang ZHANG Le ZHANG Zhengshan YAO Zhi LI Xiyao SUN Luying LIAO Xing Department of Nephropathy and Endocrine Dongzhimen HospitalBeijing University of Chinese Medicine Centre for Evidence-Based Chinese medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical Sciences Department of Endocrine One Zone Fangshan HospitalBeijing University of Chinese Medicine

OBJECTIVE: To assess the quality of Clinical practice guidelines(CPGs) in the context of diabetic kidney disease(DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of ***. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1(lowest possible quality) to 7(highest possible quality). Moreover, an overall recommendation for use was also assigned(“recommended”, “recommended with modifications” or “not recommended”). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development(33%), followed by application(36%), and stakeholder involvement(51%). The highest average score was for scope and purpose(79%), followed by clarity of presentation(75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation

关键词： appraisal of guidelines for research and evaluation II diabetic nephropathies practice guideline quality assessment systematic review

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Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

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World Journal of Diabetes 2024年第1期15卷 105-125页

作者： Wei-Long Xu Pei-Pei Zhou Xu Yu Ting Tian Jin-Jing Bao Chang-Rong Ni Min Zha Xiao Wu Jiang-Yi Yu Department of Endocrinology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pharmacy Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Pneumology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal ***-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains *** To investigate the effects of myricetin on DN and explore its potential therapeutic *** Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 ***,blood and urine indexes were assessed,along with examination of renal tissue *** morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and ***,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 *** both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and *** In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and ***,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related ***,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 ***,myricetin modulated the M1-type polarization of the RAW 264.7 *** docking and bioinformatic analyses revealed Akt as the target of *** protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inh

关键词： Myricetin Diabetic nephropathy PI3K/Akt pathway Renal tubulointerstitial fibrosis Macrophage Polarization

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