2.Targeting DNA damage response pathway: recent progress of PARP inhibitors in cancer therapy
Yu-Jing ZHENG ; Tong-Tong ZUO ; Yu-Fei FENG
Chinese Pharmacological Bulletin 2018;34(2):157-161
Genomic instability is one of the most pervasive characteristics of cancer cells,and DNA damage response (DDR) pathway plays a crucial role in genomic stability.The DDR pathway is a complex signaling network,which involves cell DNA repair,apoptosis and cell cycle regulation.Deficiencies in these repair pathways can result in several different genetic disorders,including cancer.Targeted therapy based on inhibiting the DDR pathway in cancers offers a novel therapy strategy for patients with tumors lacking specific DDR functions.Many small-mole-cule compounds targeting DDR pathway are typically developed for solid cancer therapy.The poly (ADP-ribose) polymerase (PARP) inhibitor is a kind of DDR inhibitors which exploits the principle of synthetic lethality to selectively kill cancer cells.This review highlights the molecular mechanisms of PARP inhibitor action,the progress of PARP inhibitors in cancer therapy,drug resistance and the challenge of PARP inhibitor in the future.
3.Study on regulatory effect of Danshensu on lipid metabolism of hyperlipidemia rats.
Juan CHEN ; Jun DENG ; Yu-yan ZHANG ; Jian-guo LI ; Fei-yu WU ; Hai-tong WAN
China Journal of Chinese Materia Medica 2015;40(2):313-317
OBJECTIVETo explore the effect of Danshensu on the lipid metabolism of hyperlipidemic rats.
METHODSixty clean male SD rats were selected. Twelve of them were selected in the basic control group and fed with common foods, and the remaining rats were fed with the high-fat feeds. After the successful modeling, they were randomly divided into the high-fat control group and low dose (10 mg x kg(-1) x d(-1)), medium dose (20 mg x kg(-1) x d(-1)) and high dose (40 mg x kg(-1) x d(-1)) Danshensu (dissolved in saline) groups. Both of the two groups were abdominally injected with the same volume of normal saline once a day for consecutively 30 days. The serum TG, TC, HDL-C and liver ACC1, FAS, HMGR, CPT-I mRNA expressions were detected.
RESULT AND CONCLUSIONDanshensu could inhibit the LDL-C level, timely clear redundant cholesterol and effectively regulate the lipid metablism of hyperlipidemic rats by reducing the TC content, decrease the fatty acid by reducing the FAS mRNA expression, and reduce the synthesis levels of endogenous cholesterol by inhibit the HMGR mRNA expression.
Animals ; Hyperlipidemias ; drug therapy ; metabolism ; Lactates ; pharmacology ; Lipid Metabolism ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley
4.Mechanisms of the role of fibroblast growth factor 21 in attenuating insulin resistance.
Tong-yu XU ; Wen-fei WANG ; Peng-fei XU ; Qing-yan YUAN ; Shuang-qing LIU ; Tong ZHNAG ; Gui-ping REN ; De-shan LI
Acta Pharmaceutica Sinica 2015;50(9):1101-1106
This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 μmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.
Animals
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Blood Glucose
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Diabetes Mellitus, Experimental
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drug therapy
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Diabetes Mellitus, Type 2
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drug therapy
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Diet, High-Fat
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Fatty Acids, Nonesterified
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blood
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Fibroblast Growth Factors
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pharmacology
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Insulin
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blood
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Insulin Resistance
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Mice
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Streptozocin
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Triglycerides
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blood
5.The volume of residual urine correlates with bladder outlet obstruction and detrusor contractility in patients with benign prostatic hyperplasia.
Wei-li WU ; Hua SHEN ; Kai LIAO ; Hong-bo YU ; He-tong ZHOU ; Hong-fei WU
National Journal of Andrology 2015;21(8):729-732
OBJECTIVETo identify the correlation of the volume of residual urine (VRU) with the severity of bladder outlet obstruction (BOO) and detrusor contractility in patients with benign prostatic hyperplasia (BPH).
METHODSA total of 152 patients with clinically diagnosed BPH underwent ultrasonography for measurement of the prostate volume and RVU, free uroflowmetry, and urodynamic examination for the severity of BOO and detrusor contractility. Using the software SPSS20. 0, we analyzed the correlation between the ultrasonographic results and urodynamic parameters and compared the two sample means by the t-test.
RESULTSThe prostate volume was correlated positively with BOO severity (r = 0.432, P < 0.01) and detrusor contractility (r = 0.343 , P < 0.01) while Qmax negatively with BOO severity (r = 0.327, P < 0.01) but not significantly with detrusor contractility (r = 0.123, P > 0.05). VRU showed a significantly negative correlation with detrusor contractility when > 150 ml (r = -0.490, P < 0.01), even more significantly when > 300 ml (r = -0.717, P < 0.01), but exhibited no significant correlation with it when ≤ 150 ml (r = 0.041, P > 0.05).
CONCLUSIONVRU can somehow predict the detrusor function. For patients with VRU > 150 ml, especially for those with VRU > 300 ml, the detrusor function should be evaluated and urodynamic examination is recommended for exact assessment of BOO severity and detrusor contractility.
Aged ; Humans ; Male ; Muscle Contraction ; Muscle Hypertonia ; diagnostic imaging ; physiopathology ; Organ Size ; Prostate ; diagnostic imaging ; Prostatic Hyperplasia ; diagnostic imaging ; physiopathology ; Severity of Illness Index ; Ultrasonography ; Urinary Bladder Neck Obstruction ; diagnostic imaging ; physiopathology ; Urine ; Urodynamics
6.Application of qualitative research method in clinical study on acupuncture and moxibustion.
Chinese Journal of Integrated Traditional and Western Medicine 2008;28(2):171-173
Clinical qualitative research on acupuncture has turned into one of the overseas attentive points in medical research, and up to now nearly one hundred papers have been published, covering various pivotal aspects of clinical acupuncture itself, such as therapeutic effect evaluation, experience and expectation of patients as well as understanding and experience of acupuncturists on the treatment. Currently, the qualitative research on the holistic therapeutic mode and efficacy evaluation of acupuncture has become the focus of research in foreign countries. Compared with the condition abroad, there is almost no relavent paper published in China. In this paper, the development status, focal field and main direction of overseas qualitative research on acupuncture are introduced, the characteristics of the research proposed in China is analyzed, and its future application in China is looked forward to.
Acupuncture Therapy
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Humans
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Medicine, Chinese Traditional
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methods
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Moxibustion
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Qualitative Research
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Research Design
8.Infrastructure and contents of clinical data management plan.
Tong SHEN ; Lie-dong XU ; Hai-jun FU ; Yan LIU ; Jia HE ; Ping-yan CHEN ; Yu-fei SONG
Acta Pharmaceutica Sinica 2015;50(11):1388-1392
Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.
Clinical Trials as Topic
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Data Collection
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standards
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Database Management Systems
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standards
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Information Storage and Retrieval
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standards
9.The expression and significance of glucose-6-phosphate isomerase mRNA in peripheral blood mononuclear cells of patients with rheumatoid arthritis
Guan-Fei ZHAO ; Yong-Zhe LI ; Yu-Guo SONG ; Chao-Jun HU ; Da-Wei TONG ; Shu-Lan ZHANG ;
Chinese Journal of Rheumatology 2001;0(04):-
Objective To investigate the mRNA level of glucose-6-phosphate isomerase(GPI)ex- pression in patients with rheumatoid arthritis(RA).Method Reverse transcription-polymerase chain reaction (RT-PCR)was applied to semiquantitatively analyze GPI mRNA expression in the peripheral blood mononu- clear cells(PBMCs)of 30 active RA patients,30 stable RA patients,30 patients with other rheumatic disease and 30 healthy subjects.Results There was statistically significant differences between patients with RA and other rheumatic diseases(P
10.Value of 3D-OCT in the diagnosis of macular disease before cataract surgery
Lin, LIU ; Hua, ZHENG ; Ni, LI ; Ping, TONG ; Yong-Gang, SHUI ; Lan, YU ; Shan, LIU ; Fei, SU ; Xuan-Chu, DUAN
International Eye Science 2017;17(9):1765-1767
AIM:To investigate the value of 3D-optical coherence tomography (OCT) in the diagnosis of macular disease before phacoemulsification.METHODS:Clinical records of 423 cataract patients (512 eyes) who underwent phacoemulsification combined with intraocular lens implantation in our hospital from June to December in 2015 were retrospectively analyzed.In addition to preoperative routine examination of fundus, Topcon 3D-OCT 2000 was used to examine the macula, the detection rate of macular disease was compared, risk factors of cataract combined with macular disease were analyzed.RESULTS:The OCT image results of 305 cases (384 eyes, 72.1%) were successfully obtained, 133 cases showed macular disease (146 eyes), the detection rate was 28.5% (95%CI:27.64%-29.40%);the macular disease of 35 cases (37 eyes) were detected by routine examination of fundus before operation, the detection rate was 7.2% (95%CI:6.72%-7.74%);the detection rate of 3D-OCT was significantly higher than routine examination of fundus for macular disease (χ2=79.05, P<0.01).Female, over 65 years old, surgical history of diseased eye, and high myopia were risk factors of cataract combined with macular disease, the relative risk was 1.705 (95%CI:1.091,2.664), 1.893 (95%CI:1.219,2.939), 6.593 (95%CI:2.027,21.447) and 95%CI:5.130 (2.841,9.263) respectively, the risk of cataract combined with macular disease showed an increasing trend with rising age.CONCLUSION:In preoperative examination of cataract patients, 3D-OCT has higher sensitivity in the detection of macular disease, especially for women, over 65 years old, high myopia and surgical history of diseased eye, 3D-OCT can be used as a routine preoperative examination.