To provide references for implementing drug patent strategy in China,we introduced the drug patent strategies of America,Japan and Germany,which rank the first three in the amount of patent in the world,and analyzed their successful experiences.

Objective To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) with scissors knife in difficult cases.Methods A total of 36 sessions of ESD in 34 patients were performed from May 2010 to May 2012 with application of new scissors knife.The complications and followup outcomes were recorded.Results All lesions were removed successfully with an en bloc resection rate at 91.7％.Delayed bleeding occurred in 2 patients (5.6％),and both of them were cured sucessfully with endoscopy.No perforation happened and the average hospitalization time was 5 days.Follow-up endoscopy performed 6 or 12 months after ESD in 6 patients revealed no recurrence or residual lesions.Other patients are under follow-up now.Conclusion The scissors knife is easy to manipulate,which can ensure the safety and efficiency of ESD.

Objective To analyze the impact of allograft category on the result of living related donor kidney transplantation (LRKT)and to evaluate the predominant donors. Methods A retrospective analysis of 104 recipients receiving LRKT from Apr. 2004 to Mar. 2008 was performed. Based on donor resource, all the recipient-donor pairs were divided into four groups: spousal donation group,parental donation group, sibling donation group and cousinly donation group. The observational parameters were selected for analysis, such as average post-transplant hospitalization dates, time for serum creatinine (Scr) back to normal level, Scr levels of every observational time point, incidence of major complications (infection, rejection, DGF) and recipient/graft survival rate. Results Recipient/graft survival rate of sibling donation group seemed higher. Recipients of sibling donation group seemed to have fewer post-transplant hospitalization dates, but higher rates of infection, while those of parental donation group seemed to have higher rates of rejection. Rates of rejection and infection of spousal donation group were lower than supposed. There was no statistically significant difference in time for Scr back to normal level and Set levels of every observational time point among these four groups. Conclusions The result of sibling donor renal transplantation is better, while short-term outcome of spouse donor renal transplantation is ideal, which is similar with parent or cousin donor renal transplantation. Except for human leukocyte antigen, aspects such as quality of donor kidney, predominance during operation and self-administration post-transplant are also the guarantee for the success.

Objective The purpose of this study is to assess the value of multi-slice spiral CT(MSCT)in the preoperative evaluation of living renal donor as a all in one modality.Methods Thirty-six potential living renal donors underwent the examination using a GE light VCT scanner.Informed consent was obtained from all participants.The plain scan,early arterial phase,late arterial phase and excretory phase scans are performed in the former 25 donors(injection rate 5 ml/s,total volume 100 ml,tube tension 120 kV).While in the later 11 donors(2 ml/s 40 ml+4 ml/s 60 ml),the scanning protocol included the plain scan(100 kV),vascular phase and excretory phase scans(100 kV).The excretory phase data were used in the reconstruction of CT urography in both groups.All images were reviewed by one radiologist and one urologist,and the findings of MSCT were compared with intraoperative findings for 33 donors,to investigate the utilities of MSCT in assessing renal vascularity,urinary tract and lesions of renal parenchyma.When discrepancies are found between the two reviewers,consensus was obtained via discussion.Au data was statiscally processed with SPSS for Windows.Results MSCT angiography is in accordance with intraoperative findings in demonstrating the anatomy of renal arteries and renal vein trunk,accesary arteries,early branching of renal artery.The findings from CTA are highly in accordance with the intraoperative findings,which facilitate intraoperative ligation and reduce relevant complications.CTU demonstrates the anatomy of urinary tract in good agreement with the intraoperative findings.The image quality of 3D vascularity and CTU between the two groups.scored 4.4±1.2 vs 4.2±1.3 and 4.6±0.8 vs 4.4±0.9 respectively,no statistical between-groups difference was found(Z=-0.89,-0.47,P＞0.05).Conclusion MSCT multiphase scanning combined with CTA and CTU play a important role in the evaluation of living renal donor,which preoperatively provide detailed information of renal vascularity,urinary tract and renal parenchyma as a all-in-one modality.

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.

Objective To analyze the relationship between the genetic polymorphisms of organic anion transporting polypeptide (SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA)pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations (SLCO1B3T334G, SLCO1B1 A338G) were detected in 68 recipients by PCR-LDR. The plasma samples were collected and blood concentration of MPA was measured on the 28 th day after transplantation. The area under the curve (AUC)0-12 of MPA in different genotype recipients was compared to analyze the correlation between single nucleotide polymorphisms (SNPs) and MPA pharmacokinetics. Results MPA AUC0-12 was higher in SLCO1B3 T334G GG carriers group than in TT carriers [(54. 54 ±14.40)vs(37.30±12.88)mg·h·L-1,(P=0.052)].However,there was no difference in MPA AUC0-12 among each genotype of SLCO1B1 A338G (P>0. 05). Conclusion Genetic polymorphisms of SLCO1B3 affect interindividual variety in plasma MPA concentration in Chinese kidney transplantation recipients.

Objective To investigate the change and implication of plasma osteopontin (OPN) levels in renal allograft rejection.Methods The clinical data and biological samples of 46 renal transplant recipients were analyzed rerrospecnvely,including 16 patiens with stable allograft function and no evidence of biopsy-proved rejection (Non-R),22 patients with biopsy-proved acute cellular rejection (ACR),and 8 paients with biopsy-proved chronic allograft nephropathy (CAN).Six living related donors served as healthy controls (HC).Plasma OPN level was determined by using the human OPN ELISA kit.Type and grade of ACR were diagnosed based on Banff 03 classification criteria of renal allograft pathology.The plasma OPN levels were compared among different groups.The assistant diagnostic value of plasma OPN levels in differentiating rejection patients were also evaloated.Results The plasma OPN level in HC,Non-R,CAN and ACR groups was ( 12.23 ±5.95),(19.38±8.23),(27.77± 12.27) and (41.84± 18.51) μg/L,respectively.There was no significant difference in plasma OPN levels among HC,Non-R and CAN groups (P＞0.05),but the OPN levels in ACR group were decreased significantly as compared with Non-R and CAN groups (P＜0.05 ).OPN levels were positively correlated with Banff grading of ACR (P＜0.05).OPN levels were significantly different between grade Ia and grade IIb (P＜0.05).Conclusion The change in plasma OPN level has a relationship with acute rejection.Besides,the plasma OPN levels were also positively correlated with the severity of ACR.Monitoring plasma OPN levels should be useful in predicting and evaluating the severity of ACR in renal transplant recipients.

Objective To compare the perioperative outcomes of robot-assisted partial nephrectomy (RAPN) with transperitoneal laparoscopic partial nephrectomy (LPN).Methods From July 2009 to March 2013,114 patients were treated in our hospital due to renal carcinoma,including RAPN in 45 patients and LPN in 69 patients.Their data were retrospectively reviewed.Clinical and pathological variables,R.E.N.A.L nephrometry score,operation time (OT),warm ischemia time (WIT),estimated blood loss (EBL),drainage volume,the length of hospitalization,estimated glomerular filtration rate (eGFR) outcomes,and complications were analyzed.Results There were no significant differences between the RAPN and LPN group with respect to patient age,sex,tumor laterality,size,R.E.N.A.L nephrometry score,the rate of hilar tumor and preoperative eGFR (P＞0.05).The median OT was shorter in the RAPN group than that in LPN group (165 min vs.196 min,P＜0.05).The median WIT was shorter in the RAPN than that in LPN group (21 min vs.25 min,P＜0.05).However,there were no significant differences in the postoperative eGFR and changing of eGFR within the 2 groups (P＞0.05).The rate of transfusion was similar between the RAPN (2/45) and LPN (4/69) group (P=0.72).There was also no significant difference in EBL (P=0.16).The drainage volume was also similar within two groups (167 ml vs.163 ml,P=0.81).The length of hospitalization was more favorable in the RAPN group (6.5 d vs.8.0 d,P=0.01).In RAPN group,27 cases were clear-cell carcinoma,5 cases were papillary cell carcinoma,2 cases were chromophobe cell carcinoma and 1 1 cases were angioleiomyolipoma.In LPN group,45 cases were clear-cell carcinoma,9 cases were papillary cell carcinoma,3 cases were chromophobe cell carcinoma and 12 cases were angioleiomyolipoma.There was no difference of pathological types between LPN and RAPN groups (P＞0.05).The rate of positive surgical margins was 0％ (0/45) in RAPN group and 1.4％ (1/69) in LPN group (P=0.69).The rates of complication requiring intervention (Clavien grade Ⅲ) were 2.2％ (1/45) and 2.9％ (2/69) in the RAPN and LPN group,respectively (P＞0.05).Median follow up was 12 (4-36) months in the RAPN and 13 (5-34) months in the LPN group.No local recurrence or metastasis occurred in two groups.Conclusions Early comparative outcomes suggest that RAPN has a significant benefit over the LPN in terms of OT,WIT and hospital stay.Meanwhile,it offers equivalent prognosis and postoperative renal function preservation compared with LPN.

Objective To investigate the clinical and pathologic features of patients with gastric neuroendocrine neoplasms (g-NENs).Methods A total of 50 cases of g-NENs diagnosed by pathology in the First Hospital of Jilin University from May 2012 to January 2016 were retrospective analyzed to summarize the clinical manifestations and pathological features.The location of lesion,gross morphology,maximum diameter,lymph node metastasis rate,distant metastasis rate,and survival time between patients with neuroendocrine tumors and neuroendocrine carcinomas were compared.Results Among the 50 patients,34 were males and 16 were females with a male to female ratio of 2.125 ∶ 1.Their age ranged from 33 to 77 years with an mean age of 60± 11 years.There were 13 cases (26％) of neuroendocrine tumors,31 (62％) neuroendocrine carcinomas,and 6 (12％) mixed adenoneuroendocrine carcinomas.The maximum diameter of lesion was less than 2 cm in 8 cases (16％),and equal or greater than 2 cm in 42 cases (84％).There was single lesion in 48 cases (96％) and multiple lesions in 2 cases (4％).There were 19 cases (38％) located in gastric antrum,16 (32％) in gastric body,11 (22％) in gastric fundus or cardia,3 (6％) in gastric angle,and 1 (2％) in the junction of gastric antrum and body.Thirty-two patients (64％) had metastasis,including 20 cases of lymph node metastasis and 12 cases of distant metastasis.The clinical symptoms of the patients were different,mainly were digestive system symptoms and tumor occupying symptoms,and no carcinoid syndrome was reported.The gross morphology (x2 =24.446.P =0.000).maximum diameter (t =-4.044,P =0.001),lymph node metastasis rate (x2=4.435,P =0.035),and survival time (t =2.925,P =0.000) were significantly differences between 13 cases of neuroendocrine tumors and 37 cases of neuroendocrine carcinoma.But the location of lesion (x2 =6.921,P=0.082) and distant metastasis rate (x2 =0.715,P =0.389) were no statistically different between the two groups.Conclusion Gastric neuroendocrine neoplasms can occur in any part of stomach,majority of tumor is single lesion and lack of specific clinical manifestations.The mostly gross morphology of gastric neuroendocrine carcinoma and mixed adenoneuro-endocrine carcinoma are ulcer type with a large diameter and poor prognosis.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. 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 FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.