1.Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells.
Yi WANG ; Xiao-Yu SUN ; Fang-Qi MA ; Ming-Ming REN ; Ruo-Han ZHAO ; Meng-Meng QIN ; Xiao-Hong ZHU ; Yan XU ; Ni-da CAO ; Yuan-Yuan CHEN ; Tian-Geng DONG ; Yong-Fu PAN ; Ai-Guang ZHAO
Journal of Integrative Medicine 2025;23(3):320-332
OBJECTIVE:
Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC.
METHODS:
For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC.
RESULTS:
Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway.
CONCLUSION
Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans
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Flavonoids/therapeutic use*
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Stomach Neoplasms/pathology*
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Animals
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Proto-Oncogene Proteins c-bcl-2/metabolism*
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Cell Line, Tumor
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Apoptosis/drug effects*
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Cell Proliferation/drug effects*
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Ubiquitination/drug effects*
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Mice
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Drug Synergism
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Mice, Inbred BALB C
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Mice, Nude
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Xenograft Model Antitumor Assays
;
Flavones
2.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
3.Expert consensus on the prevention and treatment of adverse reactions in subcutaneous immunotherapy(2023, Chongqing).
Yu Cheng YANG ; Yang SHEN ; Xiang Dong WANG ; Yan JIANG ; Qian Hui QIU ; Jian LI ; Shao Qing YU ; Xia KE ; Feng LIU ; Yuan Teng XU ; Hong Fei LOU ; Hong Tian WANG ; Guo Dong YU ; Rui XU ; Juan MENG ; Cui Da MENG ; Na SUN ; Jian Jun CHEN ; Ming ZENG ; Zhi Hai XIE ; Yue Qi SUN ; Jun TANG ; Ke Qing ZHAO ; Wei Tian ZHANG ; Zhao Hui SHI ; Cheng Li XU ; Yan Li YANG ; Mei Ping LU ; Hui Ping YE ; Xin WEI ; Bin SUN ; Yun Fang AN ; Ya Nan SUN ; Yu Rong GU ; Tian Hong ZHANG ; Luo BA ; Qin Tai YANG ; Jing YE ; Yu XU ; Hua Bin LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(7):643-656
4.Analysis on prevalence and epidemic risk of animal plague in different ecological plague foci in Inner Mongolia Autonomous Region.
Bo Xi LIU ; Ran DUAN ; Hao Hui WANG ; Da Yu ZHANG ; Shuai QIN ; Hong Yan LUO ; Jun LIU ; Jun Rong LIANG ; De Ming TANG ; Huai Qi JING ; Jian WANG ; Xin WANG
Chinese Journal of Preventive Medicine 2022;56(1):9-14
The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.
Animals
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China/epidemiology*
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Epidemics
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Humans
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Plague/prevention & control*
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Prevalence
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Sciuridae
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Yersinia pestis
5.Clinical efficacy of different rehabilitation modes for lumbar degenerative diseases after operation.
Xiu-Xiu SHI ; Wang-Li XU ; Jiang QIN ; Hai-Yan SUN ; Yuan HU ; Jin-Shu TANG ; Jin-Ling WU ; Jia-Liang ZHU ; Shu-Xun HOU ; Xin-Bao WU ; Wang ZHOUMOU ; Ning-Hua WANG ; Yu-Xiao XIE ; Hui ZHAO ; Xin GU ; Ming LU ; Da-Wei LI
China Journal of Orthopaedics and Traumatology 2021;34(5):406-416
OBJECTIVE:
To compare clinical effects of different postoperative rehabilitation modes on lumbar degenerative diseases, and explore influence of rehabilitation mode and other factors on postoperative effect.
METHODS:
From June 2013 to July 2016, totally 900 patients were admitted from nine tertiary hospitals in Beijing to perform single segment bone grafting and internal fixation due to lumbar degenerative diseases were prospectively analyzed. There were 428 males and 472 females, the age of patient over 18 years old, with an average of (51.42±12.41) years old;according to patients' subjective wishes and actual residence conditions, all patients were divided into three groups, named as observation group 1 (performed integrated rehabilitation approach and orthopedic treatment model intervention), observation group 2 (performed integrated rehabilitation approach and orthopedic treatment, classified rehabilitation model intervention), and control group(performed routine rehabilitation model intervention). Visual analogue scale(VAS), Oswestry Disability Index(ODI) and Japanese Orthopaedic Association (JOA) were used to evaluate postoperative efficacy among three groups at 24 weeks. Possible factors affecting the postoperative efficacy including age, age grouping, gender, body mass index (BMI), BMI grouping, education level, visiting hospital, payment method of medical expenses, preoperative complications, preoperative JOA score, clinical diagnosis, surgery section, operative method, intraoperative bleeding volume, postoperative complications and rehabilitation mode were listed as independent variables, and postoperative ODI score at 24 weeks as dependent variables. Univariate analysis was used to analyze relationship between influencing factors and postoperative efficacy. Multiple linear regression was used to analyze relationship between influencing factors, rehabilitation mode and postoperative ODI score at 24 weeks, in further to find out the main reasons which affect postoperative efficacy, and to analyze impact of rehabilitation mode on postoperative efficacy.
RESULTS:
All patients were followed up for 24 weeks after operation. All incisions healed at stage I with stable internal fixation. (1)Evaluation of postoperative efficacy:① There were no statistical differences in preoperative VAS and ODI among three groups(
CONCLUSION
Preoperative JOA score, gender, age could predict postoperative clinical effects of lumbar degenerative diseases in varying degrees treated with single level bone graft fusion and internal fixation. Different rehabilitation modes could improve clinical effects. Intergrated rehabilitation orthopedic treatment model and integrated rehabilitation approach and orthopedic treatment with classifiedrehabilitation model are superior to conventional rehabilitation model in improving patients' postoperative function and relieving pain, which is worthy of promoting in clinical.
Adolescent
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Adult
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Aged
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Female
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Humans
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Infant
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Lumbar Vertebrae/surgery*
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Lumbosacral Region
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Male
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Middle Aged
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Retrospective Studies
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Spinal Fusion
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Treatment Outcome
6.New tirucallane-type triterpenoids from the resin of Boswellia carteriiand their NO inhibitory activities.
Fang-Shen LIU ; Ting-Ting ZHANG ; Jun XU ; Qin-Xue JING ; Chi GONG ; Bang-Jian DONG ; Da-Hong LI ; Xiao-Qiu LIU ; Zhan-Lin LI ; Zhong YUAN ; Hui-Ming HUA
Chinese Journal of Natural Medicines (English Ed.) 2021;19(9):686-692
Six new tirucallane-type triterpenoids (1-6), along with ten known triterpenoids, were isolated from methylene chloride extract of the resin of Boswellia carterii Birdw. By the application of the comprehensive spectroscopic data, the structures of the compounds were clarified. The experimental electronic circular dichroism spectra were compared with those calculated, which allowed to assign the absolute configurations. Compounds 5 and 6 possesed a 2, 3-seco tirucallane-type triterpenoid skeleton, which were first reported. Their inhibitory activity against NO formation in LPS-activated BV-2 cells were evaluated. Compound 9 showed appreciable inhibitory effect, with an IC
7. Somatotype characteristics of Dong nationality adults in Hu'nan Province
Hui-Juan ZHANG ; Yi-Ming WANG ; Wei-Cheng LIAO ; Xi-Wen CHEN ; Da-Bao QIN ; Da-Yuan HUANG
Acta Anatomica Sinica 2021;52(3):465-472
Objective To investigate the somatotype characteristics of Dong adults in rural areas of Hu'nan province. Methods The Heath-Carter somatotyping method was used to study the somatotype of 749 adults (304 males and 445 females) of Dong in the rural areas of Hu'nan. Results The mean somatotype in males of Dong was endomorph- mesomorph category (4.83-4.95-1.80) and was mesomorphic endomorph category (6.09-4.68-1.37) in females. With their age increasing, the values of endomorphy decreases gradually in males, the values of endomorphy of females and mesomorphy of males and females increased at first and then decreased gradually, the values of ectomorphy of males and females decreased at first and then increased. The values of endomorphy of males were significantly lower than those of females with the same age groups, and the values of mesomorphy and the values of ectomorphy of males were significantly higher than those of females in some age groups. Compared with other ethnic groups, the values of endomorphy of Dong were larger, the values of mesomorphy were smaller, and the values of ectomorphy were in a middle level. Conclusion Adults of Dong in Hu'nan have thick subcutaneous fat, underdeveloped skeletal and muscular systems, and medium linearity. The somatotype of Dong adults in Hu'nan is close to that of Jiangsu Han, Fujian Han and Liaoning Han.
8.Research Progress of Shengjiangsan in Treating Systemic Inflammatory Response Syndrome
Yun-pu QIN ; Ming-da BI ; Shan-shan ZHANG ; Yu HAN ; Ji-hong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(23):187-192
Shengjiangsan was recorded in a medical book
9.Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.
Xiao-Ke LI ; Ming-Xiang ZHANG ; Feng-Zhen SHAO ; Da-Qiao ZHOU ; Jing-Dong XUE ; Tie-Jun LIU ; Xiao-Ling CHI ; Bing-Jiu LU ; Xian-Bo WANG ; Qin LI ; Jun LI ; De-Wen MAO ; Hua-Sheng YANG ; Hong-Zhi YANG ; Wen-Xia ZHAO ; Yong LI ; Guo-Liang ZHANG ; Yi-Ming ZHAO ; Jian-Dong ZOU ; Meng-Yang LIU ; Ke-Ke ZHANG ; Xian-Zhao YANG ; Da-Nan GAN ; Ying LI ; Peng ZHANG ; Zhi-Guo LI ; Shuo LI ; Yong-An YE
Chinese journal of integrative medicine 2020;26(5):330-338
OBJECTIVE:
To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.
METHODS:
A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.
RESULTS:
The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.
CONCLUSION
Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine
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analogs & derivatives
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therapeutic use
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Adult
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Antiviral Agents
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therapeutic use
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Double-Blind Method
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Drug Therapy, Combination
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Drugs, Chinese Herbal
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therapeutic use
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Female
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Hepatitis B e Antigens
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immunology
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Hepatitis B, Chronic
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drug therapy
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immunology
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Humans
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Male
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Medicine, Chinese Traditional
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Organophosphonates
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therapeutic use
;
Young Adult
10.Advances in the molecular mechanism of salvianolic acid and tanshinone for intervention of diabetic kidney disease
Qin-wen WANG ; Xin-xin DAI ; Xiang XIANG ; Shu-lan SU ; Jian-ming GUO ; Yue ZHU ; Da-wei QIAN ; Jin-ao DUAN
Acta Pharmaceutica Sinica 2019;54(8):1356-1363
Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetic patients, and is the leading cause of end-stage renal disease. The interaction between metabolic and hemodynamic factors leads to activation of the common pathways of diabetic kidney injury. Studies have shown that salvianolic acid can alleviate renal fibrosis and renal injury caused by diabetes by regulating renal tubular interstitial activator A, transforming growth factor-

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