Objective To investigate the correlation of CYP2D6 gene polymorphism and serum tamoxifen (TAM) and its active metabolites (4-hydroxy tamoxifen,4-OH-TAM) in terms of prognosis of breast cancer patients.Methods The oral mucosas and serum were obtained from 200 breast cancer patients receiving oral TAM from Jan 2008 to Oct 2010.Real-time RT-PCR was used to determine CYP2D6* 10 gene polymorphism.The relationship between CYP2D6* 10 gene polymorphism and clinicopathological features and prognosis was assessed by Chi-square test and Cox proportional model.Serum TAM and 4-OH-TAM concentration were determined by liquid chromatography-trap mass spectrometry (LC-MS).Results Of 200 breast cancer patients,CYP2D6 * 10/* 10 homozygotes were found in 94 cases (47％),CYP2D6 wt/wt wild type in 48 cases (24％) and CYP2D6 wt/* 10 heterozygote in 58 cases (29％).The concentration of serum 4-OH-TAM in patients with CYP2D6 wt/wt wild type and wt/* 10 heterozygote was significantly higher than that in patients with CYP2D6 * 10/ * 10 homozygote (F =4.31,P =0.01).CYP2D6 gene polymorphism was not related to clinicopathological features (P ＞ 0.05).Logrank test showed that patient's disease-free survival with mutational CYP2D6 (mean,47.2 months) was significantly shorter than that in patients without mutational CYP2D6 (mean,51.2 months) (P =0.018).Cox proportional model showed that CYP2D6 genotype was related to disease-free survival (HR =2.755,95％CI:1.230 ～6.173,P =0.014).Conclusions CYP2D6 *10/* 10 genotype is related to curative effect of TAM on breast cancer patients,detection of CYP2D6 * 10/* 10 genotype helps improve the choice of TAM therapy.

Adult ; Aged ; Carcinoma, Hepatocellular ; surgery ; virology ; Female ; Follow-Up Studies ; Glutathione ; therapeutic use ; Hepatectomy ; methods ; Hepatitis B ; blood ; drug therapy ; Hepatitis B Surface Antigens ; blood ; Hepatitis C ; drug therapy ; Humans ; Liver Neoplasms ; surgery ; virology ; Male ; Middle Aged ; Prognosis

AIM: To observe the effect of Baoxin capsules on hemodynamics of ischemic myocardium of dogs. METHODS: Fed Baoxin capsule for continuous three days, left anterior descending branch of the coronary artery of the dogs were ligated to observe the change of cardiac output, blood pressure and ?dp/dt max in different time of myocardial ischemia. RESULTS: Baoxin capsules increased the blood flow obviously, and increased left ventricular function simultaneously, the difference with ischemic group is significant (P

The human immunodeficiency virus type 1(HIV-1)can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK)signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK)pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK)pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

One hundred and twenty four patients with type 2 diabetes mellitus (T2DM) admitted to the Department of Endocrinology of Chuzhou First People's Hospital from April to October 2019 whose blood glucose levels were not controlled after treatment with metformin (2.0 g/d) for more than 3 months were enrolled in the study. The patients were randomly divided into oral drug group and liraglutide group with 62 cases in each group. On the basis of metformin, the oral drug group was treated with acarbose (300 mg/d); the liraglutide group was treated with liraglutide (1.2 mg/d). The course of treatment was 3 months. The body weight, fasting blood glucose (FPG), 2-h postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA1c), cholesterol (TC) and triglyceride (TG) levels were compared between the two groups before and after treatment, and the gastrointestinal symptoms and the incidence of hypoglycemia were analyzed. After 3-month treatment the body weight, FPG, 2 hPG, HbA1c of the two groups were lower than the baseline levels ( P<0.05). Compared with the oral group, the body weight, FPG, 2 hPG, HbA1c and TG in liraglutide group were more markedly decreased ( P<0.05). The gastrointestinal reaction of liraglutide group was significantly higher than that of the oral drug group, and there was no hypoglycemia in both groups. The data indicate that liraglutide combined with metformin can significantly improve the blood glucose, blood lipid and body weight of T2DM patients and no hypoglycemia occurs during the treatment.

OBJECTIVETo investigate the relationship between hormone sensitive lipase (HSL) gene polymorphism and aerobic endurance.

METHODSThe (CA)n repeats polymorphism genotypes in HSL intro 6 of 123 outstanding long distance runners and 127 controls of Han nationality in northern China were analyzed by PCR and Fluorescence labeled STR-genescan. Repeat polymorphisms were grouped according to segmentation point and alleles were divided into long or short chains. Chi-square test was used to analyze the frequency difference of allelic and genotypic between athlete and control groups.

RESULTS(CA) n repeats polymorphism in HSL gene was total of 9 different repeat number of alleles, which composed of 25 different genotypes. The chi-square test result showed that when compared short and long chain alleles split by 4, there was a significant difference (P <0.05) of genotype distribution in 5/10 km group compared with control. Compared the rest groups with control, there was no significant difference.

CONCLUSIONCompared short and long chain alleles split by 4, the LL genotype of (CA)n of HSL was associated with aerobic endurance and it might be a molecular marker of elite 5/10 km long distance runners.

Alleles ; China ; Ethnic Groups ; Genotype ; Humans ; Physical Endurance ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sterol Esterase ; genetics

Objective To investigate the diagnosis and the microsurgical treatment of intramedullary hemangioblastoma in cervical spinal cord.Methods The signs of MRI,and the results of operations were analysed in 26 patients with the tumors.Rusults The tumors can be classified into two types:Solid type (14 cases)and cystic type(12 eases).All the tumors underwent total removal and were all hemangioblastoma confirmed by histopathologic examinations.Postoperatively,neurological status were improved in 17 patients, remained in 7 cases and worse in 2 cases.Conclusion For intrameduUary hemangioblastoma of cervical spinal cord MRI is of significant importance in the diagnosis of localization and the nature of the tumors which is conductive to selecting appropriate operative methods.There is high risk in operating at cervical section,but microsurgical total resection is the optimal method to stop the development of the clinical presentation.Opera- tive methods varied with the different typer of the tumor.It is the most important principal that dissection is performed along the correct interface and the tumor should be removed en bloc after it is devascularized.

OBJECTIVETo investigate the effects of simvastatin (SIM)on cardiac hypertrophy and association with calcium channel modulation in rats with myocardial hypertrophy.

METHODSMyocardial hypertrophy was induced by abdominal aortic constriction (AAC) in adult SD rats. Following groups were studied (n=8 each): sham group, AAC group, AAC+ verapamil group (10 mg x kg(-1) x d(-1) per gavage for 4 weeks), AAC +SIM group (10 mg x kg(-1) x d(-1) per gavage for 4 weeks) AAC + SIM + mevalonic acid (50 mg x kg(-1) x d(-1) per gavage for 4 weeks) group. Systolic blood pressure (SBP), echocardiography, heart weight/body weight (HW/BW) and left ventricle weight/body weight (LVW/BW) ratios were measured. The protein and mRNA expressions of L-type calcium channel subunit alpha1 C and T-type calcium channel subunit alpha1 G and alpha1 H were detected by Western blot and RT-PCR respectively.

RESULTSSBP, HW/BW, LVW/BW, IVS and LVPW thickness, left ventricular weights were significantly increased in AAC rats and these effects could be significantly reduced by verapamil and SIM. The protein and mRNA expressions of alpha1 G and alpha1 H were significantly increased in AAC rats which could also be significantly inhibited by SIM or verapamil. The effects of SIM could be blocked by cotreatment with mevalonic acid. Protein and mRNA expressions of L-type calcium channel alpha1 C were similar among groups.

CONCLUSIONSimilar as verapamil, SIM could prevent AAC induced cardiac hypertrophy, possibly via inhibiting T-type calcium channel subunit alpha1 G and alpha1 H re-expression.

Animals ; Calcium Channels, L-Type ; metabolism ; Calcium Channels, T-Type ; metabolism ; Cardiomegaly ; metabolism ; prevention & control ; Male ; Myocardium ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology ; therapeutic use

BACKGROUND:Ultrasonic therapy is one of several physical therapy modalities suggested for the management of pain and loss of function due to osteoarthritis. However, its effectiveness stil remains controversial in the previous studies.
OBJECTIVE:To analyze the effect of ultrasonic therapy for the treatment of relieving knee osteoarthritis pain.
METHODS:A retrieval of Pubmed, Ovid/Medline, Ovid/EMBASE, and Cochranee database was performed. The relevant literatures were manual y retrieved. The retrieval deadline was set on March 31, 2014. Randomized control ed trials on ultrasonic therapy of knee osteoarthritis were col ected.
RESULTS AND CONCLUSION:A total of eight studies of meta-analysis were accumulated. Among them, six studies adopted visual analog scale and Western Ontario and McMaster Universities Arthritis Index, one study adopted visual analog scale only, and one study adopted Western Ontario and McMaster Universities Arthritis Index. Then the Western Ontario and McMaster Universities Arthritis Index scores were transformed into visual analog scale scores for data analysis. There was a statistical difference between the groups in the visual analog scale pain score (standardized standard deviation:-0.51;95%confidence interval:-0.68,-0.33;P=0.05). Ultrasonic therapy is an effective method for knee osteoarthritis pain.

Nitric oxide (NO), which is involved in the regulation of the cardiovascular system, nervous system, immune system, reproductive system, digestive system and other physiological activities, is an important biological substance with activity. Under normal physiological conditions, neuronal nitric oxide synthase (nNOS) can precisely regulate the nervous system NO production, release, diffusion and inactivation processes. But an excess of NO associates with the development of cerebral ischemia, Alzheimer's and Parkinson's psychosis nervous system diseases, while inhibition of nNOS activity can regulate the content of NO in vivo, and produce a therapeutic effect on some of the nervous system diseases. This review mainly describes the structure and regulation of nNOS and recent developments of small molecule inhibitors of nNOS.
Alzheimer Disease ; physiopathology ; Brain Ischemia ; physiopathology ; Humans ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; antagonists & inhibitors ; metabolism ; Parkinson Disease ; physiopathology