2.DPP-4 Inhibitor for the Treatment of Type 2 Diabetes and Intellectual Property Analysis
Xu YONG ; Huang LU ; Yang JING ; Liu QUAN ; He WEN
China Pharmacist 2015;(2):301-306
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.
3. Metabolic Disorder and Changes of Islet Morphology and Function in Thyl-aSYN Transgenic Mice
Ge GAO ; Yong-Quan LU ; Wei-Jin LIU ; Ru-Ning YANG ; Qi-Di ZHANG ; Hui YANG
Chinese Journal of Biochemistry and Molecular Biology 2021;37(2):222-228
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.
5.Silence Effect of Short Hairpin RNA on Expression of PIM-1 in Prostate Cancer Cell Lines
Xiaoguang ZHANG ; Yong XU ; Zhihong ZHANG ; Kuo YANG ; Baomin QIAO ; Changyi QUAN
Tianjin Medical Journal 2009;37(7):529-531,后插1
Objective: To investigate the interference effect of lipofectamine-mediated short hairpin RNA (shRNA) on the expression of PIM-1 gene in prostate cancer cell lines. Methods: Three kinds of recombinant plasmid expression vectors (pP[M]- hRNA-1,-2,-3) were constructed, which can produce shRNA targeting different sequence of PIM-1 mRNA. The recombinant plasmid vectors were transfected into PC-3 cell lines, respectively. RT-PCR and Western blot assay were used to detect the expression of PIM-1 mRNA and protein after transfection. Results: The expression of mRNA and protein of PIM-1 in PC-3 were inhibited significantly at 48h post-transfection. Furthermore, pPLM1- hRNA-2 and pPIM1- hRNA-3 resulted in a stronger silencing effect than that of pPIM- hRNA-1. Conclusion: The recombinant plasmid expression vector which carrying PIM-1 shRNA may remarkably inhibit the expression of PIM-1 mRNA and protein in PC-3 cell lines. The experiment provided the basis for further investigation of the role of PIM-1.
6.Determination of plasma concentration of mycophenolic acid and mycophenolic acid glucuronide by HPLC
Chunlan YANG ; Qin WANG ; Yong SU ; Quan XIA ; Guiyi LIAO ; Dujuan XU
Chinese Journal of Biochemical Pharmaceutics 2016;36(11):13-16
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.
7.Correlative study between MRI signal intensity of the lumbar intervertebral disc and collagen content in the nucleus pulposus
Wen-Chang YU ; Jian-Yong YANG ; Wen-Quan ZHUANG ; Yun-Bin CHEN ; Shi-Fang ZHENG ;
Chinese Journal of Radiology 1999;0(10):-
Objective To study correlation between MRI signal intensity of the lumbar intervertebral disc and collagen content in the nucleus pulposus.Methods Thirty-one cases with lumbar intervertebral disc herniation(male 21,female 10)received percutaneous lumbar disketetomy.Thirty-one specimens of nucleous pulposus were obtained from percutaneous lumbar disketctomy procedure and collagen content in them was measured with reformed hydroxyproline measurement method.The signal intensity(SI) of lumbar intervertebral disc and cerebrospinal fluid was measured in T_2 WI sagittal image and then ratio of disc SI to cerebrospinal fluid SI was calculated.The Pearson analysis was used to analyze the correlation between the collagen content and SI ratio and disc SI on T_2 WI.Results Collagen content and SI ratio were (231.0?63.5)mg/g and 0.19?0.07,respectively.There was negative correlation between them (r=-0.61,P
8.Preservation of continence important structures during Studer neobladder
Yong XU ; Zhihong ZHANG ; Baomin QIAO ; Changyi QUAN ; Baojie MA ; Ranlu LIU ; Kuo YANG
Chinese Journal of Urology 2010;31(5):322-324
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.
9.Value of different staging systems for gallbladder cancer
Jiandong WANG ; Xuefeng WANG ; Yong YANG ; Jun SHEN ; Weibin SHI ; Xueping ZHOU ; Zhiwei QUAN
Chinese Journal of Digestive Surgery 2010;9(2):133-135
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.
10.Impact of puboprostatic ligament-sparing during anatomic radical retropubic prostatectomy on urinary continence
Yong XU ; Zhihong ZHANG ; Baomin QIAO ; Ranlu LIU ; Kuo YANG ; Changyi QUAN ; Baojie MA
Chinese Journal of Urology 2009;30(5):340-343
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.