1.The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs
Meng-xia XUE ; Yue GU ; Jian-guo SUN ; Guang-ji WANG ; Ying PENG
Acta Pharmaceutica Sinica 2021;56(1):21-28
Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.
2.Applications of magnetic resonance cholangiopancreatography after fat meal in the preoperative evaluation of the biliary system of the donors for living liver transplantation
Peng LI ; Wen SHEN ; Hongyan NI ; Jianzhong YIN ; Miaomiao LONG ; Shuang XIA ; Qian JI ; Minghui CUI ; Tie LIU ; Ji QI
Chinese Journal of Organ Transplantation 2011;32(1):43-46
Objective To evaluate the applications of magnetic resonance cholangiopancreatography (MRCP) after fat meal in the preoperative evaluation of biliary anatomy of living liver donors.Methods Fifty cases of the preoperative donors for living liver transplantation were included and all had the corresponding intraoperative cholangiography (IOC) information. The MRCP of the donors for living liver transplantation was performed before and after fat meal (two fried eggs). The visualization and diameter of the secondary bile duct were analyzed before and after the fat meal. The results of the biliary branching pattern by MRCP after fat meal were compared with the corresponding IOC results. The accuracy, sensitivity,specificity, positive predictive value and negative predictive value of MRCP after the fat meal in distinguishing normal and any type of variant biliary anatomy were calculated. Results In all cases,82% of the 50 cases in MRCP before the fat meal could meet the diagnosis needs of the preoperative evaluation,and 100% of the 50 cases in MRCP after the fat meal could meet the diagnosis needs. There was significant difference in the demonstration quality and diameter of the secondary bile duct in MRCP before and after the fat meal (P<0. 05). MRCP showed accurate anatomy of the biliary system, using IOC as the reference standard, in 49(98%) subjects. The sensitivity, specificity, positive predictive value and negative predictive value of MRC in distinguishing normal and any type of variant biliary anatomy were 98%,94. 7%, 100%, 10% and 96. 9%,respectively. Conclusion The MRCP after fat meal can clearly demonstrate the secondary bile duct and perfectly meet the needs of the preoperative evaluation of the living liver transplantation. The MRCP after fat meal and routine MRCP should be considered complementary to one another in order to avoid complications in living liver transplantation donors.
3.Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory.
Yang YANG ; Ji-lan ZHAO ; Tian-shu HOU ; Xiao-xia HAN ; Zheng-yu ZHAO ; Xiao-hua PENG ; Qiao-Feng WU
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(10):1207-1211
OBJECTIVETo study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM).
METHODSThe UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR).
RESULTSEA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P <0.05). 1HNMR analysis showed that in the model group, contents of glutamic acid, cholesterol, very low density lipoproein (VLDL) in the pallium obviously decreased, while alanine and low density lipoprotein (LDL) significantly increased. After EA, levels of lactic acid, glutamic acid, total cholesterol (TC), and VLDL all increased, and levels of alanine and LDL decreased. All indices were approximate to those of the blank control group.
CONCLUSIONEA at Foot Yangming channel was found to have some effect on metabolites in the brain tissue of UC model rats, which had specific metabonomic material basis and mechanism based on the Pi/Wei-brain related theory.
Acupuncture Points ; Animals ; Cerebral Cortex ; metabolism ; Colitis, Ulcerative ; Electroacupuncture ; Lipids ; Male ; Rats, Sprague-Dawley
4.Application of non-bioartificial liver combined with liver transplantation in treating mid-or end-stage chronic serious hepatitis
Jie XIA ; De-Dong XIANG ; Zhan-Yu YANG ; Nan ZHANG ; Peng GUO ; Ji-Jun ZHOU ; Yu-Ming WANG ;
Chinese Journal of Infectious Diseases 2007;0(07):-
Objective To evaluate the application of non-bioartificial liver support system (ALSS) combined with liver transplantation(LT) in treating mid-or end-stage chronic severe hepati- tis.Methods ALSS plus liver transplantation were employed in treating 28 patients with mid-or end- stage chronic severe hepatitis.Clinical data from the patients before and after treatment were collect- ed.The survive rate of ALSS plus LT group were compared with that of medication group 99 cases and medication plus ALSS group 30 cases.The data were analyzed with t test and X~2 test.Results After 57 times ALSS treatment,the serum total bilirubin(TBil),prothromin time(PT),bile acid, blood urea nitrogen(BUN),creatnine(Cr) and ammonia of all the 28 patients got improved(P 0.05).The clinical symptoms and signs of the patients were ameliorated at median 3 d(1~153 d). All patients were bridged to liver transplantation successfully after median 20 d(1~153 d).The 3 and 6 months post-operation survival rate of ALSS plus LT group(71.4%,71.4%) were significantly higher than those in medication group(18.2%,11.1%) and medication plus ALSS group(36.7%, 26.6%)(P
5.Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil.
Jin-Xia LI ; Man ZHANG ; Li-Bo SUN ; Ling ZHANG ; Wen-Quan ZHANG ; Hai-Fu ZHAO ; Peng-Ling LI ; Yong-Li HUA ; Peng JI ; Yan-Ming WEI
China Journal of Chinese Materia Medica 2014;39(7):1293-1299
Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.
Angelica sinensis
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chemistry
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metabolism
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Animals
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal
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analysis
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metabolism
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pharmacology
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Energy Metabolism
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drug effects
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Lipid Metabolism
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drug effects
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Male
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Metabolomics
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Oils, Volatile
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analysis
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metabolism
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pharmacology
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Plant Oils
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analysis
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metabolism
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pharmacology
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Rats
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Rats, Wistar
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Urine
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chemistry
6.NR6A1 promotes vascular smooth muscle cell apoptosis by up-regulating RIPK3 gene expression
hui Ya ZHANG ; Xiong WANG ; ying Sheng WU ; xia Ji PENG ; yun Fu WU ; Jing KE ; Peng ZHANG ; fang Qiu ZHANG ; xia Yan LV
Chinese Journal of Pathophysiology 2017;33(9):1581-1586
AIM:To determine the role of nuclear receptor subfamily 6,group A,member 1 (NR6A1) in vascular smooth muscle cell (VSMC) apoptosis.METHODS:NR6A1 protein was over-expressed in the VSMCs by infection of adenovirus.The effect of NR6A1 on the viability of VSMCs was measured by MTT assay.DAPI staining,TUNEL staining and caspase activity assay were conducted.DNA microarray was used to quickly screen the target genes of NR6A1.The effect of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) silencing on NR6A1-induced apoptosis of the VSMCs was further analyzed.RESULTS:Adenovirus-mediated over-expression of NR6A1 induced the apoptosis of VSMCs.The RIPK3 gene expression was up-regulated by NR6A1 over-expression in the VSMCs.NR6A1-induced VSMC apoptosis was inhibited by RIPK3 silencing.CONCLUSION:NR6A1 promotes VSMC apoptosis by up-regulating the RIPK3 gene expression.
7.Hybrid external fixator combined with limited internal fixation for the treatment of high-energy tibial plateau fractures.
De-fu YANG ; Gong-lin ZHANG ; Ming ZHANG ; Li-ping XIA ; Ji-hua HE ; Jun-yang PENG
China Journal of Orthopaedics and Traumatology 2009;22(3):219-220
Adult
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Aged
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External Fixators
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Female
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Fracture Fixation, Internal
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methods
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Humans
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Male
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Middle Aged
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Tibial Fractures
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surgery
8.Anti-inflammatory effect and mechanism of artemisinin and dihydroartemisinin.
Wan-ying YU ; Wei-juan KAN ; Peng-xia YU ; Min-min LI ; Ji-shuai SONG ; Feng ZHAO
China Journal of Chinese Materia Medica 2012;37(17):2618-2621
OBJECTIVETo study and compare the anti-inflammatory effect and molecular mechanism of artemisinin and dihydroartemisinin.
METHODMouse mononuclear macrophage RAW264.7 cells were stimulated to release inflammatory mediators such as TNF-alpha, IL-6 and NO, in order to assess the drugs' inhibitory effect on macrophage's release of above inflammatory mediators. The levels of TNF-alpha and IL-6 were determined by ELISA and the cytotoxicity was determined by MTT method. The protein expression of iNOS, COX-2 and beta-actin were tested by Western blot. The enzymatic activity of COX-2 was determined by colorimetric method.
RESULTDihydroartemisinin significantly inhibited LPS-induced release of TNF-alpha, IL-6 and NO from RAW264.7 in mice with the concentration range of 12.5 - 100 micromol x L(-1), and showed good dose dependence. Artemisinin only inhibited the IL-6 release to a certain extent.
CONCLUSIONDihydroartemisinin inhibits macrophages from releasing inflammatory factors TNF-alpha and IL-6 and inflammatory mediators NO by down-regulating iNOS protein. Artemisinin may help dihydroartemisinin to show its anti-inflammatory effect through metabolism.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Artemisinins ; pharmacology ; Cell Line ; Gene Expression ; drug effects ; Inflammation Mediators ; immunology ; Interleukin-6 ; genetics ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; Nitric Oxide ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology
9.A comparison of tissue formation and the content of polysaccharide between wild and cultured Dendrobium candidum.
Jun-an FAN ; Ji-sheng WANG ; Yan ZHANG ; Ling-yan REN ; Zong-ying QIU ; Yong-peng XIA
China Journal of Chinese Materia Medica 2005;30(21):1648-1659
OBJECTIVETo compare the tissue formation and the content of polysaccharide between the wild Dendrobium candidum and the cultured ones and to find any existed differences.
METHODBare-handed microtomy and photomicrography; The content of polysaccharide is determined by phenol-sulphuric acid method.
RESULT AND CONCLUSIONThere are no marked noticeable differences between the wild D. candidum and the cultured ones in terms of the tissure formation and the content of polysaccharide.
Dendrobium ; anatomy & histology ; chemistry ; growth & development ; Plant Stems ; anatomy & histology ; chemistry ; growth & development ; Plants, Medicinal ; anatomy & histology ; chemistry ; growth & development ; Polysaccharides ; analysis ; Tissue Culture Techniques
10.Dynamic analysis of major active ingredients of Cortex Moutan cultivated in Dianjiang county of Chongqing.
Jun-an FAN ; Yan ZHANG ; Yong-peng XIA ; Zong-yin QIU ; Chao YU ; Ji-sheng WANG ; Bin-hao WANG
China Journal of Chinese Materia Medica 2007;32(15):1501-1504
OBJECTIVETo study the change of paeonol and paeoniflorin, the two major active ingredients contained in Cortex Moutan cultivated in Dianjiang county of Chongqing, due to the change of some influence factors, and explore suitable plant conditions and quality cotrol methods of Cortex Moutan.
METHODPaeonol and paeoniflorin were determined by HPLC in samples from Dianjiang.
RESULT AND CONCLUSIONThe ratio of paeonol and paeoniflorin in Cortex Moutan was regularly influenced by altitude, the growth years and harvest time. Cortex could be cultivated at altitude of 400 m to 800 m but 600 m is the best aria because of the peak of the percentage composition of paeonol and paeoniflorin at 600 m. The first and middle third of October in the fifth year is the best picking time of Cortex Moutan because of the maximum of the percentage composition of paeonol and paeoniflorin.
Acetophenones ; analysis ; Altitude ; Benzoates ; analysis ; Bridged-Ring Compounds ; analysis ; China ; Drugs, Chinese Herbal ; chemistry ; Glucosides ; analysis ; Monoterpenes ; Paeonia ; chemistry ; Plant Bark ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Seasons ; Soil