Tumor growth is dependent on angiogenesis.At present,antiangiogenic treatment has been one of the most studied and exploited targets for molecular cancer therapy.Up to date,anti-angiogenesis drugs,which has already been applicated in clinic widely,include bevacizumab,endostar,multi-target tyrosine kinase inhibitor such as sorafenib and sunitinib.The main adverse effects associated with antiangiogenic therapy include hypertension,cardiotoxicity,thrombosis,bleeding,proteinuria,impaired wound healing,gastrointestinal perforation,lassitude,diarrhoea,hand foot shin response,etc,the later three is common in sorafenib and sunitinib.The majority of adverse effects are generally mild to moderate in severity and tolerated by patients.although there are specific,uncommon events that are severe and can be lifethreatening.

Objective:To introduce a programmed death-1 (PD-1) inhibitor nivolumab used as a new antitumor agent. Methods:According to the literatures, the action mechanism of nivolumab and the clinical trial results on the main indications approved or being investigated in phase III trials were reviewed and evaluated. Results:Nivolumab could restore the antitumor activity of T cells through binding with PD-1 and consequently blocking its interaction with the key ligands of PD-L1 and PD-L2. Several completed and ongoing clinical trials showed that nivolumab used alone or combined with chemotherapy or CTLA-4 inhibitor ipilimumab exhibited better effica-cy when compared with current clinical used chemotherapy drugs in the treatment of melanoma, non-small cell lung cancer and renal cell carcinoma. Nivolumab was well tolerated during the treatment with such main grade 3-4 adverse events as immune-mediated pneu-monia, abnormal liver functions and fatigue. Conclusion:Through its anti-tumor immune response, nivolumab can improve the clinical efficacy in the treatment of various tumors including melanoma, non-small cell lung cancer and renal cell carcinoma.

Objective:To observe the effect of Yulin mixture on ovarian function in rats with kidney-yang deficiency ovulatory dysfunction.Methods:The hydrocortisone-induced ovulation disorder rat models were established,and the rats were divided into the model control group,Yulin mixture group and positive control group (clomiphene citrate group),and the normal control group was set up,and 10 rats were in each group.The general situation of the rats was observed.The wet weight indices of uterus and ovary were measured by an electronic analytical balance.Serum estradiol (E2),progesterone (P),follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay.Ovarian morphology was observed after HE staining.Results:Yulin mixture could improve the general status of ovulation disorder rats,increase the wet weight indices of uterus and ovary (P<0.05) and the levels of serum E2,P,LH and FSH (P<0.01),and improve the pathological state of ovarian morphology.Conclusion:Yulin mixture can improve the levels of serum E2,P,LH and FSH resulting in promoting ovarian development.

Objective To study the relationship between ghrelin gene polymorphisms and type 2 diabetes.MethodsAll subjects were genotyped for these two single nucleotide polymorphisms(C408A,G346A)of ghrelin by PCR-RFLP assay.Anthropometric variables,blood glucose,insulin,lipid,uric acid and other clinic parameters were measured.Results In control group,the genotype frequencies are as follows:CC 75.4%(n=251),CA 24.0%(n=80),and AA 0.6%(n=2).In type 2 diabetes group,the genotype frequencies are as follows:CC 70.8%(n=143),CA 28.2%(n=57),and AA 1.0%(n=2).There was no significant differences of the genotype frequencies in two groups.In control group,serum total cholesterol in subjects carrying CC genotype was higher than that of subjects without CC genotype(P

In coloreetal cancer,there are multiple abnormally expressed microRNA (miRNA),suggesting that the miRNA may be involved in tumor development process.Recently,more and more evidence shows that miRNA are more stable in the blood,compared with mRNA,which makes circulating miRNA are helpful to become the non-invasive tumor marker for the diagnosis,treatment and prognosis evaluation in coloreetal cancer.

OBJECTIVE:To evaluate drug utilization of inpatients in neurology department of our hospital.METHODS:Category of drugs,consumption amount,consumption sum and administration time for each person of 853 cases in neurology department of our hospital in 2008 were analyzed retrospectively.RESULTS:Of total 853 inpatients,patients with stroke accounted for 82.8%.The first 3 drugs in the list of consumption amount were Nao'an capsule,folium ginkgo tablet and Shuxuetong injection.The first 3 drugs in the list of consumption sum were Shuxuetong injection,Monosialoganglioside injection and Cobamamide for injection.Aspirin tablet,Nao'an capsule and Cobamamide for injection took up the first 3 places in the list of DDDs.CONCLUSION:Inpatients in neurology department mainly suffer from cerebrovascular disease and are treated with TCM for activating blood and eliminating stasis and nervous system agents,They are also treated various complications such as infection,constipation,hypertension,diabetes and so on.Drug use in the clinic is rational.

OBJECTIVE: To analyze the current situation and developing trend of drugs used in 10 hospitals of Hunan Province from 1996 to 2000, and to serve as reference for drug production, marketing and clinical application .METHODS:The sum of money and percentages of different kinds of drugs used each year were added up separately.RESULTS: The sum of money of drugs consumed was increasing at a rate of 18% each year.About 40% of the money was spent on anti - infective drugs and 20% on imported drugs.CONCLUSION: The sum of money of drugs consumed will grow year by year .The clinical use of drugs will be more rational and of more choices,but the sum of money spent on imported drugs will decrease.

Objective To evaluate the effect of puerarin on melanogenesis in melanocytes,and to explore its possible mechanisms.Methods Third-to fifth-passage melanocytes isolated from human foreskin were treated with different concentrations (1,5,10,20,40,80 and 160 μmol/L) of puerarin for 24 hours,with those receiving no treatment as the normal control group.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate the proliferative activity of melanocytes,a sodium hydroxide solubilization method was used to measure melanin content,and reverse transcription PCR (RT-PCR) and Western blot analysis were performed to quantify the mRNA and protein expressions of microphthalmia-associated transcription factor (MITF),tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) respectively.Results There were no significant differences in the proliferative activity of melanocytes between the puerarin (1-40 μmol/L) groups and normal control group (P ＞ 0.05),and 40 μmol/L was chosen as the concentration of puerarin for subsequent experiments.Compared with the normal control group,the 40-μmol/L puerarin group showed increased melanin content as well as mRNA and protein expressions of MITF,TYR and TRP-1 (all P ＜ 0.05).Concretely speaking,the protein expressions of MITF,TYR and TRP-1 in the 40-μmol/L puerarin group were increased by 8.69％,10.28％ and 10.58％ compared with the normal control group respectively (all P ＜ 0.05),and their mRNA expressions were 2.48,1.91 and 1.63 times higher in the 40-μmol/L puerarin group than in the normal control group respectively (all P ＜ 0.05).Conclusion Puerarin can increase the mRNA and protein expressions of MITF,TYR and TRP-1,and promote melanogenesis in melanocytes.

Objective To evaluate the relationship between proportion of PR1 specific cytotoxic T lymphocytes (CTLs) in the peripheral blood and prognosis and curative effect in patients with HLA-A0201 positive chronic myelogenous leukemia (CML),and to discuss whether PR1 peptide could be used as the following immune therapeutic method for patients who had achieved the standard of stop treatment.Methods The soluble HLA-A0201/PR1 tetramer and flow cytometry were applied to determine the proportion and the frequency of PR1 specific CTLs in peripheral blood from 28 HLA-A0201 positive CML patients.The proportions were compared among different phases of patients.The correlations between the proportion of PR1 specific CTLs and clinical parameters were analyzed.Results There was a negative correlation between PR1 specific CTLs and PCR (bcr-abl/abl)Is (r =-0.658,P ＜ 0.001).The frequencies of PR1 specific CTLs at 3-month,6-month,9-month,12-month,2-year,3-year,4-year,5-year,6-year were (0.06±0.02) ％,(0.10± 0.02) ％,(0.14±0.02) ％,(0.16±0.02) ％,(0.20±0.03) ％,(0.18±0.03) ％,(0.18±0.01) ％,(0.17±0.05) ％ and (0.18±0.03) ％,respectively.The frequency of PR1 specific CTLs at 3-month,6-month or 9-month was statistically different compared with that of the other time spots (P ＜ 0.05),and there were no statistical differencies among the frequencies at 1-year,2-year,3-year,4-year,5-year,6-year (P ＞ 0.05).For patients treated with IM 400 mg qd,the frequency of PR1 specific CTLs in high-risk group was lower than that in low-risk or intermediate-risk groups.Conclusion PR1 specific CTLs can be detected in patients who achieved good curative effect,and is correlated with tumor burden,which indicates that PR1 specific CTLs may be related to the action of resisting leukemia and provide the evidence for PR1 peptide as a potential immune therapeutic schedule in patients who have achieved stable MR45 and MR50.

Objective To investigate the effect of batroxobin on the blood-retinal barrier (BRB) and vascular endothelial growth factors (VEGF) in diabetic rats. Methods Sixty Sprague-Dawley rats were used to establish diabetic models by intraperitoneal injecting with streptozotocin (60 mg/kg), and were divided into 3 groups: diabetic group (n=20), batroxobin (40 mg/kg) group (n=20) and batroxobin (20 mg/kg) group (n=20). Twenty-five else rats were in control group. All of the rats were executed 7 days later. The function of BRB was observed by Evans blue method. Results concentration of VEGF protein was detected by enzyme-linked immunoabsorbert assay (ELISA). The results of each group were compared. Results The content of BRB leaked into retina was obvious lower in the control group than which in the other 3 diabetic groups(P0.05). The content of Evans blue was lower in the 2 diabetic groups with different dosage of batroxobin than which in the control group (P