Exendin-4,a peptide analogue of glucagon-like peptide-1(GLP-1),is presently in clinical trials as a therapy for type 2 diabetes mellitus.Exendin-4 selectively acts on GLP-1 receptors,which are coupled to the cAMP nucleotide second messenger pathway to enhance the survival and plasticity of neurons in the brain.Exendin-4 has potent effects on homeostasis of Ca2+,on multiple targets to block apoptotic signaling pathways,and on neuronal proliferation and differentiation.It has also been demonstrated to possess properties against oxidative stress and excitotoxicity.In this review the functions of exendin-4 on central nerve system and the potentia therapeutic effects on neurodegenerative diseases will be involved.

BACKGROUND:The assessment for long-term efficacy of chronic ischemic disease is more important than the short-term efficacy assessment, which associates with patient’s long-term quality of life and long-term survival rate. OBJECTIVE:To observe the 5-year folow-up outcomes of autologous bone marrow stem cel transplantation for the treatment of thromboangitis obliterans. METHODS:This study enroled 43 patients of thromboangitis obliterans who underwent autologous bone marrow stem cel transplantation from August 2007 to January 2010 in the Department of Thyroid Vascular Surgery, the First Affiliated Hospital of Xinjiang Medical University. At 1, 2, 3, 4 and 5 years after transplantation, pain, cold sensation, and intermittent claudication distance were folowed up by telephone; changes in limb ulcers were observed. At 1 year after transplantation, venous oxygen partial pressure and oxygen saturation of limbs were reviewed. RESULTS AND CONCLUSION:A total of 38 thromboangitis obliterans patients with complete folow-up data were included in the final analysis. Compared to the preoperation, pain, cold sensation, and intermittent claudication significantly improved. The difference was statisticaly significant (Z values:-4.277,-5.086,-3.574, P < 0.001). Compared with 1-5 years after operation, pain and cold sensation had no statisticaly difference (P >0.05). Intermittent claudication distance had increased. Differences in terms of intermittent claudication distance was statisticaly significant (Z=43.898,P < 0.001). Significant differences in venous oxygen partial pressure and oxygen saturation were detected between preoperation and 1-year posttransplantation (tvalues: 36.790, 43.964,P values: 0.040, 0.037). Above results suggest that autologous bone marrow stem cel transplantation for thromboangitis obliterans obtained stable long-term outcomes.

Objective To study the therapeutical effect of glutathione(GL),a powerful antioxidant on the symptoms and ECG in patients with coronary heart disease and its mechanisms.Methods Eighty-five subjects with coronary heart disease were recruited(45 male and 40 female).The patients were randomized to receive GL (240 mg,ivgtt,qd,for 14 days,n=44)on the top of conventional treatment(aspirin+?-blocks+ACEI)or conven- tional treatement alone(control,n=41).The serum MDA,SOD,NO levels were determined.Electrocardio- graphy(ST stage,T wave)was examined.Results GL significantly improved clinical symptoms scores(2.0+0.5 vs control:1.5+0.5,P

Objective To identify the isolated rat bone marrow derived mesenchymal stem cells(MSCs),and evaluate the efficiency of adenoviral vector expressing human urokinase type plasminogen activator(uPA) in transfection of rat MSCs and its effect on proliferation of MSCs. Methods MSCs were isolated and purified by pasted wall purification,and were identified by immunicytochemistry.The transfection efficiency of uPA was detected by fluorescent microscopy,the expression of uPA in MSCs was detected by Western blotting,and the proliferation of MSCs was evaluated by MTT. Results The harvested MSCs exhibited the typical appearance of MSCs,and it was revealed by immunohistochemistry that the expression of MSCs markers CD29 and CD90 was positive,while that of CD34 and CD45 was negative.A tendency of increase in expression of green fluorescent protein(GFP) was observed with increase of multiplicity of infection(MOI).After transfection with AduPA for 72 h,the transfection efficiency reached(94.0?1.5)% at MOI of 80,and positive GFP cells could still be observed even after 7 d.The transfected uPA had no effect on the proliferation of MSCs. Conclusion MSCs are favourable genetic vectors to express uPA,and can be used for treatment of liver fibrosis.

OBJECTIVETo observe the effect of Zhibai Dihuang Decoction (ZDD) on mRNA and protein expressions of transient receptor potential family vanilloid subtype 1 (TRPV1) and transient receptor potential family vanilloid subtype 5 (TRPV5) in Ureaplasma urealyticum (UU)-infected rat semens and spermatogenic cells, and to explore the pathomechanism of UU-infected infertility and the intervention of ZDD.

METHODSTotally 45 were randomly selected from 60 4-5 months old SD rats. UU testicular infected animal models were set up after bladder inoculation of UU suspension. The remaining 15 rats were simultaneously injected with normal saline as a normal control group. After a successful modeling, UU infected model rats were randomly divided into the model group, the azithromycin group, and the ZDD group, 15 in each group. Rats in the ZDD group were administered with ZDD at the daily dose of 1 g/kg by gastrogavage. Rats in the azithromycin group were administered with azithromycin suspension at the daily dose of 0. 105 mg/kg by gastrogavage. Equal volume of normal saline was administered to rats in the normal control group and the model group. All medication was performed once daily for 21 successive days. Testes and epididymis were extracted after rats were killed and UU positive rates were compared among all groups. Sperm cells were separated using a mechanical separation technique. Sperm motility parameters were detected using color sperm motion detection system. mRNA and protein expressions of TRPV1 and TRPV5 in spermatogenic cells were determined by real-time quantitative PCR and Western blot.

RESULTSThe UU positive rate was obviously higher in the model group than in the normal control group [(86.7% (13/15 cases) vs. 0] P < 0.05). It was lower in the ZDD group [33.3% (5/15 cases)] and the azithromycin group [26.7% (4/15 cases)] than in the model group (P < 0.05). Compared with the normal control group, class A and B sperms were reduced, the linear velocity and the average velocity were significantly lowered, mRNA and protein expressions of TRPV1 and TRPV5 in spermated genic cells significantly decreased in the model group (P < 0.05). Compared with the model group, class A and B sperms were increased, linear and curve velocities and the average velocity were significantly elevated, mRNA and protein expressions of TRPV1 and TRPV5 significantly increased in the ZDD group and the azithromycin group (P < 0.05, P < 0.01). Compared with azithromycin group, class A and B sperms were increased, the linear velocity and the average velocity were significantly elevated, mRNA and protein expressions of TRPV1 and TRPV5 significantly increased in the ZDD group (P < 0.05, P < 0.01).

CONCLUSIONZDD could fight against UU infection and elevate semen quality, which might be associated with up-regulating mRNA and protein expressions of TRPV1 and TRPV5 in spermatogenic cells.

Animals ; Calcium Channels ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Infertility ; Male ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Semen Analysis ; Sperm Motility ; Spermatozoa ; TRPV Cation Channels ; metabolism ; Testis ; Ureaplasma Infections ; Ureaplasma urealyticum

Objective To study the changes and significance of the frequencies of circulating follicular helper T cells (cTfh) and circulating regulatory follicular T cells (cTfr) as well as the cTfh/cTfr ratio in neuromyelitis optica spectrum disorder (NMOSD).Methods The frequencies of cTfh,cTfr and B cells in patients with NMOSD and health controls(HCs) were measured by flow cytometry.Enzyme-linked immunosorbent assay was used to detect the level of IL-21 and AQP4-Ab in patients and HCs.Results The frequencies of cTfh and B cells,the cTfh/cTfr ratio and the plasma level of IL-21 werc significantly higher in the relapsing patients than those in the remitting patients and HCs(P ＜ 0.05),and the cTfr level in the relapsing patients was lower than that in the remitting patients and healthy population (P ＜ 0.05).But no statistical differences were observed in the above indexes between the remitting paticnts and HCs.There was also no significant difference in AQP4-Ab level between the patients with relapse and remission (P ＞ 0.05).The frequency of cTfh in the patients wasc positively correlated with the level of B cells and IL-21(P ＜ 0.05),and the frequency of cTfr was negatively correlated with B cells and IL-21 (P ＜ 0.05).The ratio of cTfh/cTfr was positively correlated with B cell frequency and IL-21 level (P ＜ 0.05).AQP4-Ab level had no correlation with the frequencies of cTfh cells and B cells,cTfh/cTfr ratio and IL-21 concentration (P ＞ 0.05).Conclusion The changes in the frequencies of cTfh and cTfr as well as the imbalanced cTfh/cTfr ratio may promote the activation of humoral immunein NMOSD and participate in the pathogenesis of this disease.

OBJECTIVETo evaluate the effectiveness of manual therapy and traction for lumbar disc herniation and analyze the current status of this kind of randomized clinical trial (RCT).

METHODSDatabase of CNKI, VIP, WANFANG, PubMed and OVID were searched. Some relevant journals were manually retrieved. A total of 2 874 literatures on manual therapy and traction for lumbar disc herniation were collected, of which 17 articles met the inclusion criteria. The Jadad score scale was used to evaluate the quality,and RevMan5.0 was used for meta-analysis of literatures.

RESULTSThe results of the meta-analysis of all trials involved were as followed:the combined effect of the effective rate was RR = 1.10, 95% CI [1.06, 1.14], the combined effect of the cure rate was RR = 1.36, 95% CI [1.21,1.52], the combined effect of the VAS was RR = 1.37, 95% CI [1.28, 1.45], the combined effect of the JOA was RR = 4.75, 95% CI [4.40, 5.09].

CONCLUSIONThe overall quality of the current RCT researches about manual therapy for lumbar disc herniation was lower,and did not support the conclusion that manual therapy was more effective than traction for lumbar disc herniation.

Humans ; Intervertebral Disc Displacement ; surgery ; therapy ; Lumbar Vertebrae ; surgery ; Musculoskeletal Manipulations ; methods ; Randomized Controlled Trials as Topic ; Traction ; methods

OBJECTIVETo compare the clinical curative effect of thoracolumbar burst fracture treated by the posterior unilateral approach corpectomy fusion screw-rod fixation and anterior corpectomy bone fusion screw plate fixation.

METHODSFrom January 2008 to May 2014,36 cases of thoracolumbar burst fracture underwent operation of decompression, fusion, and internal fixation was retrospective analyzed. Among them, 16 patients were treated through posterior approach as posterior group, including 13 males and 3 females aged from 37 to 62 years old; 9 cases caused by falling injury, 3 cases by traffic accident injury,4 cases by heavy aboved;the injury segment was on T₁₂ in 2 cases, L₁ in 5 cases, L₂ in 7 cases, L₃ in 2 cases; according ASIA grade, 3 cases were grade A, 2 cases were grade B, 2 cases were grade C, 5 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 5 to 15 days. Other 20 patients were treated through anterior-lateral approach as anterior-lateral group, including 15 males and 5 females with age from 27 to 62 years old; 12 cases caused by falling injury, 4 cases by traffic accident injury, 4 cases by heavy aboved; the injury segment was on T₁₂ in 2 cases, L₁, in 7 cases, L₂ in 9 cases, L₃ in 2 cases; for ASIA grade: 4 cases were grade A, 2 cases were grade B, 4 cases were grade C, 6 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 4 to 12 days. The operation time, bleeding during operation and postoperative drainage volume were observed in two groups,and the changes of nerve function of ASIA grade, clinical efficacy,improved degree of thoracic and lumbar lordosis,and bony fusion were compared between two groups.

RESULTSAll patients were followed up from 12 to 24 months with an average of (15.8 ± 3.3) months. The operation time, bleeding during operation, and postoperative drainage volume had no significant different between two groups (P > 0.05). As compared with preoperative, ASIA grade of two groups at last follow-up had statistically significantly different (P < 0.01), the neural function of two groups after operation was recovered for different extent. The JOA score of two groups was compared between last follow-up and preoperative, the difference had statistically significant (P < 0.01), the two groups showed good clinical effect. The clinical results of ASIA grade, JOA score and RIS had no significant differences between two groups. All patients of two groups were obtained fusion. Thoracic and lumbar lordosis angle improvement degree had no significant difference between two groups ,it bad significant difference had statistical significance compared with preoperative, the two approaches could effectively restore the spinal sequence.

CONCLUSIONFor patients with thoracolumbar burst fracture just treated by anterior decompression and reconstruction of anterior column, according to the degree of operation performer' skill proficiency and the patient' condition to choose, but for patients must performed the spinal canal decompression anterior and posterior, the three column-reconstruction to required anterior-posterior approach, the posterior unilateral approach corpectomy fusion screw-rod fixation obviously shorten operation time, reduce the operation wound, it is worth the clinical promotion.

Adult ; Decompression, Surgical ; methods ; Female ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Reconstructive Surgical Procedures ; Retrospective Studies ; Spinal Fractures ; surgery ; Spinal Fusion ; methods ; Thoracic Vertebrae ; injuries ; surgery

Objective To analyze the characteristics of auditory verbal memory impairment in mild Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI).Methods Auditory verbal memory test was performed in 72 patients with MCI,45 patients with mild AD,and 62 normal controls.Results Significant intergroup differences were found in total former five free recall and learning scores,The MCI subjects( 16.4?5.5,2.6?1.7)performed significantly more poorly than the normal control subjects(NC) (30.2?5.6,3.4?1.9),and mild AD categories (9.8?4.1,2.0?1.2) showed lower results than the MCI subjects(t=2.26,P

Objective To determine the frequency of polymorphism at exon 26 (C3435T) of muhidrug resistance 1 gene (MDR1) in epileptic patients in the southern Chinese and to study the association of this polymorphism with pharmacoresistance.Methods DNA samples were obtained from 134 patients,of whom 72 were resistant to antiepileptic drug treatment and 62 were responsive to the treatment. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction (PCR) followed by restriction digestion and gel electrophoresis.Genotype and allele frequencies in the drug resistant group were compared to those in the response group by Chi-square analysis.Results Of all 134 patients,33 (24.6%) had CC genotype,72 (53.7%) had CT genotype,and 29 (21.6%) had TT genotype.The frequency of CC genotype was significantly higher in the pharmaeoresistance group (33.3%) than that in the responsive group (14.5%,P=0.012).The frequency of the C allele was also significantly higher in the pharmacoresistance group (57.6%) than that in the responsive group (44.4%,P=0.03).When patients were divided by types of seizure into three groups:generalized seizure group,partial seizure group,and undefined seizure group,the CC genotype and C allele were associated with pharmacoresistance in the partial seizure group.Conclusions In the southern Chinese,the CC genotype and C allele are associated with resistance to the antiepileptic treatment.This finding needs to be verified in studies with larger sample size.