Glucagon-like peptide-1 protects against cardiac microvascular endothelial cells injured by high glucose

Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase.

Relationship between abnormal vagus nerve tension and basal ganglia cerebral infarction induced paroxysmal atrial fibrillation

Objective: To investigate the relationship between basal ganglia cerebral infarction and paroxysmal atrial fibrillation(PAF) caused by abnormal vagus nerve tension.Methods: A total of 1 483 cases of elder patients with cerebral infarction who received head CT or MRI examination during the period were enrolled, including 830 male and613 female, with the average age as 78 years. These cases were divided into basal infarction ganglia group(n = 1 045) and non-basal ganglia infarction group(n = 438)according to the anatomic site of cerebral infarction. The differences of the incidence of PAF, left atrial diameter and heart rate variability were compared between the two groups.Results: In basal ganglia infarction group, the incidence rate of PAF was significantly higher than that of non-basal ganglia infarction group(P < 0.05). The incidence trend of cerebral infarction in basal ganglia was age-related, in the >79 years basal ganglia cerebral infarction group, the incidence of PAF was significantly higher than that of nonbasal ganglia infarction group(P < 0.05). There was no significant difference in the left atrial diameter between the basal ganglia infarction group and non-basal ganglia infarction group. Basal ganglia cerebral infarction patients with high PAF had higher heart rate variability than non-basal ganglia infarction group.Conclusion: Elderly patients with basal ganglia infarction have high incidence of PAF.Sympathetic nerve damage in cerebral basal ganglia, increased vagal tension and cardiac vagal tension are the direct causes of PAF. The results indicates that the increased central vagal nerve tension mediated PAF probably is an indication of supplying sympathetic neurotransmitter or cardiac vagal denervation treatment.

Optimization of Hydrolysis Conditions for the Isolation of Angiotensin-I Converting Enzyme(ACE) Inhibitory Peptides from Rhopilema hispidum

To obtain the maximum angiotensin-I converting enzyme(ACE) inhibitory activity, the protein hydrolysis conditions of the jellyfish Rhopilema hispidum were optimized using response surface methodology(RSM). Trypsin was selected to produce R. hispidum protein hydrolysates(RPH) with ACE inhibitory activity. The optimal parameters for producing protein hydrolysates with the highest ACE inhibitory activity were as follows: hydrolysis time 5 h, hydrolysis temperature 50℃, and the enzyme-to-substrate ratio 6%. Under these conditions, the ACE inhibitory rate of RPH could reach 64.28% ± 5.72%. In addition, RPH contained high levels of Gly, Glu, Pro, Ala, Asp and Arg, with a molecular weight distribution range of 0.32–6.84 kDa. The following three novel ACE inhibitory peptides were isolated and identified: Ile-Gly-Glu-Thr-Gly-Pro, Gly-Ala-Thr-Gly-Pro-Ala-Gly-Tyr-Val and Gly-AlaPhe-Gly-Pro-Gly-Gly-Leu-Val-Gly-Arg-Pro. The IC_(50) values of the ACE inhibitory activity of these three purified peptides were 19.07, 27.42 and 31.26 μmol L^(-1), respectively. These results suggested that proteins and peptides isolated from R. hispidum could be utilized as antihypertensive functional food sources.

Biomechanical study of modular hemipelvic endoprosthesis for Type I-IV defect of pelvic tumor

Background： The modular hemipelvic prosthesis has been used in patient of Type I-IV pelvic tumor with good outcomes, but how to keep the stability between the prosthesis and the residual sacrum is a problem. An additional screw-rod system seems to solve it, but its biomechanical characters are still not well understood, which need experimental evaluation. Methods： Six pelvic specimens were prepared in three conditions （normal intact pelvis, ＂normal＂; the pelvis of left Type I-IV defect and implanted with prosthesis without/with additional screw-rod system, ＂rod-＂ and ＂rod＋＂）. Compressing biomechanical experiments （50-500N） were performed in these three conditions, respectively. Results： The loadings during the experiments are in accordance with the linear elastic control mode. Under the increasing loading, the implanted pelvises displaced asymmetrically, unlike normal intact pelvis. The vertical displacement of ＂rod＋＂ changed significantly, whereas ＂rod-＂ did not. For both implanted pelvis, right side displaced less than left side （P values 〈0.05）. Conclusions： The implanted pelvis showed asymmetric displacement under loading, where healthy side displaced more. The implanted pelvis plus screw-rod system showed less displacement at implanted side but more at contralateral side in comparison with those without screw-rod system.

Liver, biliary and pancreatic injuries in pancreaticobiliary maljunction model in cats

BACKGROUND： Pancreaticobiliary maljunction is a high risk factor of pancreatitis and biliary tract cancer. How this maljunction affects the liver remains obscure. This study aimed to examine the effects of pancreaticobiliary maljunction on the liver, pancreas and gallbladder in a cat model.METHODS： A model of choledocho-pancreatic side-to-side ductal anastomosis was created in ten cats. Before the procedure,a small piece of tissue from the liver, pancreas and gallbladder was collected as a control. The common channel formation was checked by cholecystography. The livers, pancreases and gallbladders of these cats were harvested for histological examination. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. RESULTS： Seven of the 10 cats survived for 6 months after surgery. The color of the liver was darker in the PBM model than the control specimen, with nodules on the surface. Histological examination showed ballooning changes and inflammatory infiltrations and the histopathological score increased significantly（P〈0.05）. Also, mitochondria swelling and lipid droplet in cytoplasm were observed under an electron microscope. The pancreas also appeared darker in the PBM model than the control specimen and dilated pancreatic ducts were found in three cats. Histopathological examination revealed vascular proliferation and inflammatory infiltration with numerous neutrophils. Gallbladder epithelial cells were featured by expanded endoplasmic reticulum, increased intercellular space and cellular nucleus deformation. The positive cells ofproliferating cell nuclear antigen were increased significantly（P〈0.05）. CONCLUSION： The present study demonstrated that pancreaticobiliary maljunction can lead to the injuries of the liver, pancreas and gallbladder.

Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their apoptosis.In in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis.

Regulation of microbiota–GLP1 axis by sennoside A in diet-induced obese mice

Sennoside A(SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet(HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR(homeostatic model assessment for insulin resistance) and glucose tolerance test(GTT). SA restored plasma level of glucagon-like peptide 1(GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids(SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota–GLP1 axis to improve glucose metabolism in the obese mice.

Subtrochanteric femur fracture treated by intramedullary fixation

Purpose： To discuss surgical technique, operative efficacy and clinical outcome of intramedullary fixation in the treatment of subtrochanteric femur fractures. Methods： From February 2011 to February 2013, 76 cases of subtrochanteric femur fractures were treated by intramedullary fixation in our hospital, including 53 males and 23 females, with the age range of 37 -72 years （mean 53.5 years）. According to Seinsheimer classification, there were 2 cases of type I, 7 type Ⅱ, 15 type Ⅲ, 23 type IV and 29 type V. Firstly, all patients underwent closed reduction with the guidance of C-arm fluoroscopy in a traction table. Two cases of type I and 3 cases of type Ill fractures had ideal closed reduction followed by internal fixation. The others needed additional limited open reduction. Radiographic examination was used to evaluate callus formation and fracture healing in postoperative 1, 3, 6 and 12 months follow-up. Functional recovery was evaluated by Harris Hip Scoring （HHS） system. Results： Patients were followed up for 6-12 months. All fractures were healed except one patient with delayed union. The average bone union time was 4.5 months. According to HHS system, 65 cases were considered as excellent in functional recovery, 8 good, 2 fair and 1 poor. The proportion of the patients with excellent and good recovery was 96.05%. Conclusion： Intramedullary fixation is feasible for the treatment of subtrochanteric femur fracture. The accuracy of intraoperative reduction and surgical skill are important for the clinical outcome and the patients＇ prognosis.

Neuropsychological features in post-stroke cognitive impairment with no dementia patients with different Traditional Chinese Medicine syndromes

OBJECTIVE: To investigate neuropsychological features of post-stroke cognitive impairment with no dementia(PSCIND) patients with different Traditional Chinese Medicine(TCM) syndromes.METHODS: We recruited 50 patients with PSCIND between April 2012 and March 2013. Patients were divided into different groups according to TCM classifications. Patients were assessed using neuropsychological tests, including cognitive screening(mini-mental state examination), memory testing (auditory verbal learning test), executive/attention[shape trails test, stroop color-word test(SCWT),reading the mind in the eyes test, the digit ordering test-A(DOT-A), and symbol digit modalities test], language(action naming test, Boston naming test, famous face test, similarity test, and verbal fluency test), and visuospatial functioning [complex figure test(CFT)].RESULTS: We found no significant differences between patients with and without a diagnosis of turbid phlegm blocking the upper orifices on neuropsychological test performance. Patients diagnosed with upper hyperactivity of liver Yang syndrome scored significantly lower on the SCWT-C executive test and the CFT-delayed recall memory test. Patients with excess syndrome scored significantly lower on the SCWT-C executive test, and significantly higher on the DOT-A executive test.CONCLUSION: Neuropsychological characteristics differ between PSCIND patients with different TCM classifications.

Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals

Propofol (2,6-diisopropylphenol) has been widely used in clinical surgery because of its fast induction and rapid recovery effects (Miller et al., 2014). Although the underlying mechanisms are still controversial, many studies have focused on the augmentation of GABA-induced inhibition and/or modulation of glycine receptor channel activity. However, inhibition of glutamatergic synaptic transmission may also contribute to general anesthesia. The effects of general anesthetics are significantly enhanced when glutamate receptor antagonists are co-administered (Ishizaki et al., 1996).

Biomarkers for diabetes prediction, diagnosis and personalized therapy

Diabetes mellitus （DM） is one of the most common ＇metabolic disorders in the world~ in which more than90% are grouped to type 2 DM （T2DM）.1 T2DM is characterized by decreased insulin sensitivity and impaired insulin secretion2 leading to hyperglycemia, and the serum glucose has been used as a golden standard for diabetes diagnosis. However, T2DM is a kind of disease involving defects of multiple organs, which cannot be distinguished through the measurement of the serum-glucose level. In addition, T2DM is a multiple-stage disease, which usually covers several decades from impaired plasma glucose to various complications. The serum-glucose level only reflects the consequence of multiole physiological disorders in the Riven stare.

Management of Lisfranc injury with anterolateral calcaneal compression fracture

To the Editor:The mechanism of Lisfranc injury is complex and may cause different patterns of fractures or dislocation of the midfoot complex.Abduction force injury is a special injury pattern,which may cause the fracture or(and)dislocation of the lateral column of the Lisfranc joint,especially the cuboid.[1,2,3]However,the anterolateral calcaneus is less commonly involved.Since the fragment of the calcaneocuboid(CC)joint facet is too uncon-spicuous to manifest on a plain X-ray,and surgeons always pay more attention to the Lisfranc joint,anterolateral calcaneal compression fracture and even Chopart joint injuries are often overlooked,which may lead to a delayed surgical management,chronic foot deformities,and functional disability.

Serum Levels of RBP4 Might Not Be Determined by Diabetes Mellitus but by Kidney Function and Renal Replacement Therapy

It has been reported that retinol-binding protein 4(RBP4) is associated to adiposity,insulin resistance,and type 2 diabetes.Meanwhile,circulating RBP4 levels are also affected by renal function.The aim of the present study is to investigate whether serum levels of RBP4 are primarily associated with different stages of chronic kidney disease(CKD) or type 2 diabetes,if there is more potential relevance between RBP4 and renal replacement therapy.The serum levels of RBP4 were assessed by commercial competitive enzyme-linked immunosorbent assay(ELISA)kit in 212 patients with the CKD stages 1—5 and in 24 healthy controls,while its correlation with clinical and metabolic parameters was analyzed.The serum level of RBP4 had a strong correlation with estimated glomerular filtration rate(e GFR)(P < 0.001).Stratified by e GFR and treatment,no more differences in RBP4 serum concentration were detected between type 2 diabetic and non-diabetic subjects [CKD stages 1—5,non-dialysis(ND),hemodialysis(HD) and peritoneal dialysis(PD);P > 0.05 for all].The elevation of RBP4 become higher in HD than in PD and ND in CKD5 patients(P = 0.008 and P = 0.04,respectively),while there was no significant difference between PD and ND groups.Multivariate linear regression analysis demonstrated three independent predictors of e GFR(β =-0.676,P < 0.001),C-reactive protein(CRP)(β =-0.573,P < 0.001) and creatine(β = 0.509,P = 0.024) in the study population.The study results demonstrated that the serum level of RBP4 was negatively related to the e GFR,whether diabetes mellitus(DM) affected the blood concentration of RBP4 or not.And the serum level of RBP4 exhibited significant difference in different renal replacement therapies.