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.

Objective: Extracting ephedrine and berberine from the water extract of Ephedra Herba and Rhizoma Coptidis. Methods: Modified PVA was used as separating membrane and separated alkaloids. Results: A colorless ephedrine aqueous solution was obtained when extraction time was less than 8 hours; while a three constitution solution was obtained when time of extraction is over 8 hours. So is Rhizoma Coptidis. The membrane is hardly fouled. Conclusion: Purity of alkaloids from Herba Ephedra and Rhizoma Coptidis by membrane separation is Superior to that by alcoholic sediment but amount of alkaloids is reverse.

Objective To analyze the MRI imaging feature and the clinical feature of pituicytoma. Methods The clinical data and imaging feature of 10 patients with pituicytoma who were proved histologically were retrospectively studied. Visual disturbances disorder and headache were the main complaints of all patients. One patient had sexual function decline. All patients were given the examination of MRI and showed saddle area were occupied. Results Most of pituicytoma was circular or oval morphologically. Pituicytoma located at suprasellar region in 4 patients, in the sellar in 2 patients and over the sellar region in 4 patients.In them, cystic change occured in 1 patient. In most of the cases, the tumor showed isointensity on T1WI, isointensity or slightly hyperintensity on T2WI. After injection of contrast medium, the tumor showed homogeneous enhancement in early stage. Pathological markers:S-100, and vimenlin indicated 100%positive;glial fibrillary acidic protein(GFAP), synaptophysin (SYN) and epithelial membrane antigen(EMA) indicated 50% positive. Six patients′serum endocrine function test:the levels of serum total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (FSH), luteinizing hormone (LH) had different degrees of reduction in 4 patients, and these index were normal in 2 patients. Conclusions On MRI, pituicytoma has certain characteristics which might help clinical diagnosis combined with the clinical manifestation and endocrine function tests.

Objective To evaluate the feasibility of monitoring the gene expression of VEGF165 via the diglycylcysteine (GGC) reporter gene system by reporter probe of 99Tcm-GH. Methods DNA fragments encoding GGC binding motifs were prepared by PCR and positioned at the C end of VEGF165 gene after the linearization of pcDNA3-VEGF165 plasmid. A replication-defective adenovirus vector Ad5-VEGF165GGC motif-internal ribosomal entry site(IRES) -enhanced green fluorescent protein (EGFP) (Ad5-VIE)was constructed, with a cytomegalovirus (CMV) early promoter driving the expression of VEGF165 gene,GGC motif and EGFP, under the aid of an IRFS. A replication-defective adenovirus carrying the Ad5-EGFP was used as the control. Mensenchymal stem cells (MSC) were infected with the recombinant adenovirus at a multiplicity of infection (MOI) from 0 to 100 infectious units (0,10,25,50,100). The cellular uptake of 99Tcm-GH in infected MSC were then studied at 30, 60, 90 and 120 min. VEGF165 was detected by quantitative reverse transcriptase real-time PCR (RT-PCR), Western-blot, and immunohistochemisty. EGFP was observed by RT-PCR and fluorescence microscopy. The correlation analysis was studied between the cellular uptake of 99Tcm-GH and the expression of VEGF165. SPSS 13.0 was applied for statistical analysis. Independent samples t-test, q-test and Pearson correlation coefficient were used. Results After infected with different viral titer of Ad-VIE, the cellular uptake of 99Tcm-GH increased with the increasing virus titer(r2 =0.86, P ＜0.05), with the peak rate (7.94 ±0.75) % at MOI = 100. In time-dependent uptake study, the cellular uptake rates increased rapidly with the time extension, and the highest uptake occurred at 120 min with the peak uptake rate (7.72 ±0.22)%. The uptake rates of 99Tcm-GH in Ad5-VIE-infected cells were significantly higher than those of Ad5 -EGFP-transfected cells at all time points (t = 15.10- 54.92, all P ＜0.05). The VEGF165 and EGFP mRNA levels increased with increasing virus titer, and the VEGF165 mRNA correlated well with the EGFP mRNA(r2 = 0. 99, P ＜ 0.05). After infected with different MOI of Ad5-VIE, good relationship was found between the cellular uptake of 99Tcm-GH and the expression of VEGF165protein in MSC(r2 =0.90, P ＜0.05). Inmunohistochemisty showed VEGF165 protein expressed obviously at Ad5-VIE-infected MSC, and the EGFP was observed by fluorescence microscopy. Conclusions The cellular uptake of 99Tcm-GH in Ad5-VIE-infected MSC are well correlated with the expression of VEGF165 in vitro. The expression of therapeutic gene VEGF165 can be monitored by the GGC peptide expression.

The autophagy is a process of cell survival by lysosomal degradation of damaged organelles and macromo-leular materials. It plays an important role in stable environment. The autophagy of cells is persisted in the patho-physiology of angiogenesis. However,To explore the development of the angiogenesis based on autophagy,is the clinical treatment ideas of the vascular disease.

The autophagy is a process of cell survival by lysosomal degradation of damaged organelles and macromo-leular materials. It plays an important role in stable environment. The autophagy of cells is persisted in the patho-physiology of angiogenesis. However,To explore the development of the angiogenesis based on autophagy,is the clinical treatment ideas of the vascular disease.

OBJECTIVETo study the correlation between lumber disc degeneration and sacroiliac joint disorder, in order to provides a new understanding concepts and therapeutic approach for the prevention and treatment of chronic intractable low back pain.

METHODSFrom August 2009 to October 2010,129 cases with lumbar disc herniation were studied with epidemiological methods. Among them, 61 patients with L4, disc herniation included 37 males and 24 females, ranging in aged from 20 to 75 years old, duration of the disease ranged from 1 to 144 months; The other 68 patients with L5S1 disc herniation included 32 males and 36 females,ranging in aged froml8 to 76 years old,duration of the disease ranged from 0.5 to 240 months. The clinical data, symptoms and signs,X-ray characteristics of lumbar spine and pelvis of the patients were investigated by epidemiological. The risk of lumbar disc herniation was calculated with case-control study; independent variables were screened with single factor analysis; the risk factors for lumbar disc herniation were determined with logistic regression analysis, and biomechanics analyses were taken.

RESULTSAmong 129 patients with lumbar disc herniation, 88 cases associated with sacroiliac joint disorders, sacroiliac joint disorder was a risk factor of lumbar disc herniation (OR = 4.61, P = 0.00); 47 cases associated with sacroiliac joint disorders in 61 patients with L4,5 disc herniation, iliac crest uneven caused by iliac rotational displacement was a high risk factor of L4,5 disc herniation (OR = 11.27, P = 0.00); 41 cases associated with sacroiliac joint disorders in 68 patients with L5S1 disc herniation, lumbar sacral angle abnormalities caused by sacral tilt shift was a high risk factor L5S1 disc herniation (OR = 2.31, P = 0.03).

CONCLUSIONLumbar disc herniation and sacroiliac joint disorder are two of fallot, the two factors affect each other and there is a causal relationship. They are common exists in low back pain.

Adult ; Aged ; Biomechanical Phenomena ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; Joint Diseases ; physiopathology ; Lumbar Vertebrae ; physiopathology ; Male ; Middle Aged ; Sacroiliac Joint ; physiopathology

AIMTo elevate the encapsulation efficiency, decrease the burst release and improve the release of protein entrapped in poly (lactic-co-glycolic acid) (PLGA) microspheres. The bovine serum albumin (BSA) composite microspheres of alginate-chitosan-PLGA were prepared and the release characteristics of BSA from this composite microspheres were studied.

METHODSThe much smaller calcium alginate microcapsules were first prepared by a modified emulsification method in an isopropyl alcohol-washed way and coated with chitosan, then the alginate-chitosan microcapsules were further entrapped in PLGA to form the composite microspheres. The protein concentration was determined using a BCA protein assay kit. The release profiles were changed with various formulation factors.

RESULTSThe average diameter of the composite microcapsules was about 30 microm. Comparing with 60% to 70% of the conventional PLGA microspheres, the average encapsulation efficiency was more than 80%, and the burst releases in phosphate buffer solution of the composite microspheres decreased from 40% and 50% to 25% and further to 5% in saline solution.

CONCLUSIONThe novel composite microspheres were prepared, the drug encapsulation efficiency increased and the burst release decreased. The desired release profiles could be obtained by regulating the ratios of PLG and PLA in the composite microspheres.

Alginates ; chemistry ; Chitosan ; chemistry ; Drug Delivery Systems ; methods ; Lactic Acid ; chemistry ; Microspheres ; Particle Size ; Polyglycolic Acid ; chemistry ; Polymers ; chemistry ; Serum Albumin, Bovine ; chemistry

OBJECTIVETo study the biomechanical relationship between iliac rotation displacement and L(4,5) disc degeneration, and to provide clinical evidences for the prevention and treatment of L(4,5) disc degeneration and herniation.

METHODSFrom March 2012 to February 2014,68 patients with lumbar disc herniation combined with sacroiliac joint disorders were selected. Among them, 42 patients with L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78 +/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc herniation combined with sacroiliac joint disorders included 11 males and 15 females, ranging in age from18 to 65 years old with an average of (45.53 +/- 27.23) years old, and the duration of the disease ranged from 0.5 to 103 months with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken. The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc thickness were studied by using linear and regression methods. The hiomechanical analysis was performed.

RESULTSThere was a positive correlation between pelvic tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49, P=0.00). There was a causal relationship and good linear proportional relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative correlation between lumbar scoliosis and intervertebral space in male patients with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship and good linear proportional relationship in the two variables (Y=13.09-0.27X, P=0.02). But there was a positive correlation between lumbar scoliosis and intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04).

CONCLUSIONIliac rotational displacement are closely related with L(4,5) disc degeneration and herniation in biomechanics. A new concepts and therapeutic approach is provided for clinical treatment of chronic and refractory herniation of L(4,5) disc in patients

Adult ; Biomechanical Phenomena ; Female ; Humans ; Intervertebral Disc Degeneration ; physiopathology ; Intervertebral Disc Displacement ; physiopathology ; Lumbar Vertebrae ; physiopathology ; Male ; Rotation ; Sacroiliac Joint ; chemistry ; physiopathology ; Young Adult

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Hemorrhagic Fevers, Viral ; epidemiology ; Hospitalization ; Humans ; Male ; Middle Aged