DPP-4 inhibitors are new oral hypoglycemic drugs and hot spots developed and launched in recent years, and they pro-vide new choices for the clinical treatment of type 2 diabetes. In China, DPP-4 inhibitors that are approved to use in the treatment of type 2 diabetes are all imported products currently. In the paper, the current intellectual property situation of DPP-4 inhibitors that are developed and approved at home and abroad is researched and analyzed. Reasonable use of the patent information of DPP-4 inhibitors that is about to expire or have failed can provide good guidance for the subsequent development of DPP-4 inhibitors in domestic with promising curative effect and good market prospects, and can generate new patents in order to enhance the market competitiveness.

Child ; Community-Acquired Infections ; epidemiology ; Humans ; Pneumonia ; epidemiology

Parkinson's disease (PD) is the second major neurodegenerative disease.The pathogenesis of PI) is still unclear.It is generally believed that neural damage, mitochondrial dysfunction, inflammation, oxidative stress and autophagy dysfunction caused by the transmission and aggregation of a- synuclein play an important role in the occurrence and development of PD.More and more research show- that metabolic disorder is one of the pathogenesis of PD.We examined whether overexpression of a- synuclein could induce metabolic disorder in mice and the possible mechanisms.Mice were divided into two groups: Thyl-aSYN transgenic mice (TG) and the control wild-type (WT) group.The rotarod test was used to analyze motor function in mice.We detected the body weight, plasma insulin content, glucose tolerance and insulin tolerance in the two group mice.The morphology of islets in the two groups were observed by hematoxylin eosin (HE) staining, and the islets were isolated to detect the glucose- stimulated insulin secretion (GSIS).The results showed that compared with the WT group, exercise tolerance of 12-month-old TG group decreased by 23.1% (P < 0.05) , body weight increased by 7% (P < 0.01), glucose tolerance decreased (P < 0.05), insulin tolerance decreased (P < 0.05), and insulin contents in the peripheral blood decreased by 20% (P < 0.05).Compared with the WT group, the levels of ce -syn proteins in the pancreas of the TG group increased by 1.32 times (P < 0.05) , the area of islets in the TG group decreased (P < 0.05 ) , the number of islets decreased (P < 0.01) , and the insulin secretion function decreased (P< 0.01).This study showed that the role of a-synuclein in PD is not limited to the damage of dopaminergic neurons, it also can affect metabolism and the morphology and function of peripheral organs, which provides a new theoretical basis for the pathogenesis of PD.

Objective To develop an HPLC method for the determination of mycophenolic acid(MPA), mycophenolic acid glucuronide(MPAG) in plasma.Methods The samples were precipitated with zinc sulphate-methanol solution before injection.Carbamazepine was selected as internal standard,ZORBAX XDB C18 (4.6 mm ×250 mm,5 μm) column was used and the flow rate was 1 mL/min.The mobile phase consisted of methanol-acetonitrile-potassium dihydrogen phosphate buffer solution(gradient elution) .The column temperature was 30℃ and the detective wave length was 254 nm.And then the MPA,MPAG concentration of 32 patients in 7-14 days after renal transplantion were determined.Results The assay was linear within 0.2-50μg/mL for MPA, 2.5-500 μg/mL for MPAG(r>0.999).Absolute recovery rates of MPA,MPAG were more than 80%, the recoveries were between 90%-110%.The intra-day and inter-day RSDs were both lower than 10%.Totally 32 cases of renal transplantion patiens were with mycophenolate mofetil at the dose of 1-1.5 g/d,and MPA in plasma was within the range of 0.32-6.19μg/mL,MPAG in plasma was within the range of 9.52-149.25μg/mL.Conclusion The method is accurate, convenient and rapid, which could be used in the quantitative determination of plasma concentration of MPA,MPAG in renal transplantion patients.

OBJECTIVE:To explore the clinical related factors of leucopenia induced by azathioprine in the treatment of inflam-matory bowel disease (IBD). METHODS:Clinical information of 114 IBD patients were collected from our hospital during Jan. 2013-Mar. 2015. Steady concentration of AZA metabolite 6-thioguanine(6-TGNs)in red blood cell was determined by HPLC. The correlation of patient’s gender,age,diseases,AZA daily dose and blood concentration of 6-TGNs with leucopenia induced by AZA were investigated. The optimal critical value of leucopenia could be predicted with ROC curves. RESULTS:Among 114 IBD patients,40 patients suffered from leucopenia(35.1%). There was no statistical significance in the proportion of leucopenia among patients with different age,gender,diseases and AZA daily dose(P>0.05). There was statistical significance in the proportion of leucopenia among patients with different concentrations of 6-TGNs(P<0.05). Mean blood concentration of 6-TGNs in leukopenia patients [(407.82±262.88)pmol/(8×108)RBC] was higher than patients with normal leukocyte level [(275.85±118.37)pmol/(8× 108)RBC],with statistical significance(P<0.05). ROC curve predicted that the optimal critical value of leucopenia was blood con-centration of 6-TGNs>291.04 pmol/(8 × 108)RBC. CONCLUSIONS:AZA induced leucopenia may be related to the concentration of 6-TGNs in red blood cell of IBD patients,and high concentration of 6-TGNs is risk factors of leucopenia. Clinicians can provide AZA individual treatment for IBD patient to reduce the occurrence of leucopenia according to routine blood test and the concentra-tion of 6-TGNs.

Objective To detect the mutation of CARD15 gene in a patient with sarcoidosis and tuberculosis.Methods Clinical data were collected from a 32-year-old male patient with early-onset sarcoidosis and tuberculosis.Peripheral blood was obtained from the patient,both of his parents,and 102 healthy controls.All the 12 exons of the coding regions as well as flanking intronic sequences of the CARD15 gene were amplified by PCR followed by direct sequencing.The resulted sequences were blasted against the reference sequences of CARD15 gene.Results Both clinical features and histopathological findings of the patient were consistent with sarcoidosis.Furthermore,the patient presented with flexion contractures of fingers and toes,as well as iridocyclitis.A heterozygous missense recurrent mutation c.1000C ＞ T (p.R334W) was detected in exon 4 of the CARD15 gene in the patient,but not in either of his parents or any of the 102 healthy controls.Conclusions A p.R334W mutation in the CARD15 is identified in the patient,which may be responsible for the clinical phenotype of earlyonset sarcoidosis.Gene analysis may be a useful method to clarify the etiology of early-onset sarcoidosis.

Objective To investigate the efficacy of regional lymphadenectomy for patients with T2 gallbladder cancer. Methods From January 1990 to December 2009, 48 patients with T2 gallbladder cancer received regional lymphadenectomy following radical surgery at the Xinhua Hospital of Shanghai Jiaotong University, and their clinical data were retrospectively analyzed. Patients were divided into two groups according to the range of lymphadenectomy. Standard group (23 patients): lymph nodes in the regions of bile duct, common bile duct and hepatoduodenal ligament were dissected; extended group (25 patients): lymph nodes in the regions of hepatoduodenal ligament, head of pancreas, duodenum, portal vein, common hepatic artery and celiac axis were dissected).The condition of patients in the two groups were compared after the treatment. The morbidity and survival rate were analyzed by using Fisher exact test and Kaplan-Meier method, respectively, and the survival rates between the two groups were compared by using Log-rank test. Results No perioperative death was found in the two groups. The morbidities was 17% (4/23) in the standard group and 24% (6/25) in the extended group, with no significant difference between the two groups ( P ＞ 0.05 ). The 5-year cumulative survival rate and median survival time were 40% and 29.8 months in the standard group, and 66% and 53.2 months in the extended group, with significant differences between the two groups ( x2 = 4. 687, P ＜ 0.05 ). Conclusion Extended regional lymphadenectomy should be performed on patients with T2 gallbladder cancer if the primary lesions can be dissected radically.

Objective To investigate the effects of preserving continence important structures during Studer pouch surgery. Methods Radical cystectomy and Studer orthotopic neobladder surgeries were performed on 68 male patients with muscle invasive bladder cancer.The anatomic configuration of the rhabdosphincter complex,pudendal nerve supply,and musculofascial support system to the proximal urethra were carefully preserved.The neobladder functions were then evaluated. Results The pathological classification of the 68 patients was as follows:T3a N0M0 in 20 cases and T2N0M0 in 48 cases.The patients were followed up for 6 to 36mon(mean 12 mon).Complete urinary continence was achieved in 67 patients 24 hours a day and the remained one had nocturnal incontinence.Of these patients,59 patients could urinate well without residual urine and the other 9 patients had residual urine of 20 to 30 ml. Conclusions A well-performed Studer pouch should pay specific attention to the anatomic configuration of the rhabdosphincter complex,pudendal nerve supply,and musculofascial support system to the proximal urethra to achieve the goal of maximizing continence preservation.

Objective To discuss the value of different staging systems for gallbladder cancer.Methods The clinical data of 132 patients with gallbladder cancer who had been admitted to Xinhua Hospital from October 1992 to December 2006 were retrospectively analyzed.The clinical stage and postoperative survival of patients in each stage were analyzed by Nevin staging system,staging systems of AJCC 5th and 6th edition.The survivals of patients were analyzed by Kaplan-Meier method and the comparison between groups was analyzed by Log-rank test.Results According to the Nevin staging system,the accumulative survivals of patients with stages Ⅰ,Ⅱ,Ⅲ,Ⅳ or Ⅴ were 80.3%,75.6%,43.2%,16.2% and 6.5%,respectively.The accumulative survivals of patients with stages Ⅰ,Ⅱ or Ⅲ were significantly higherthan those with stages Ⅳ or Ⅴ(χ~2=7.239,6.152,3.992,12.354,13.171,15.084,P＜0.05).According to the AJCC 5th edition staging system,the accumulative survivals of patients with stagesⅠ,Ⅱ,Ⅲ or Ⅳ were 71.4%,40.9%,10.2% and 5.8%,respectively.The accumulative survivals of patients with stages Ⅰ or Ⅱ were significantly higher than those with stages Ⅲ or Ⅳ (χ~2=18.286,23.729,5.541,13.607,P＜0.05),and the survivals of patients with stage Ⅲ were significantly higher than those with stage Ⅳ (χ~2=7.758,P＜0.05).According to the AJCC 6th edition staging system,the accumulative survivals of patients with stages Ⅰ,Ⅱ,Ⅲ or Ⅳ were 51.1%,11.7%,8.2% and 6.5%,respectively.Patients with stages Ⅰ or Ⅱ had a comparatively low survival,while the survivals of patients with stage Ⅰ were significantly higher than those with stages Ⅱ,Ⅲ or Ⅳ(χ~2=15.300,21.956,31.397,P＜0.05).Patients with stage Ⅱ had a higher survival than those with stage Ⅳ(χ~2=8.789,P＜0.05).There was no significant difference in survival between patients with stage Ⅱ and Ⅲ,and between patients with stage Ⅲ and Ⅳ.Conclusions The AJCC 5th edition staging system is still the perfect staging system of gallbladder cancer.The Nevin staging system is not integrating enough,while AJCC 6th edition staging system is too strict.

Objective To evaluate the contribution of puboprostatic ligament-sparing technique in urinary continence after radical retropubic prostatectomy (RRP). Methods A total of 74 men with clinically localized prostate cancer underwent RRP. Of whom, 50 patients were performed pubo-prostatic ligament-sparing technique(group A), while 24 patients were not(group B). Patients were evaluated by independent observer questionnaire to determine their urinary continence status. Results Mean patient age [(61.3±2.4) vs (60.8±2.1)years], serum prostate-specific antigen (PSA) values [14.3±1.2)ng/ml vs (14.7±1.3) ng/ml], operative time [(110.5±10.4)min vs (109.7±10.6) mini, estimated blood loss [(250.5±23.4) ml vs (253.4±22.3) ml], and positive surgical margin rate (6% vs 8%) were not significantly different between group A and B(P>0.05). The urinary con-tinence rate with the puboprostatic ligament-sparing technique at 1-year follow-up was significantly higher than that of the control group (P<0.05). Concision The puboprostatic ligament-sparing technique significantly enhances post-operative urinary continence after RRP.