Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes

Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me｜litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion.     

Protective effect of diosmin against diabetic neuropathy in experimental rats

OBJECTIVE： The present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats. METHODS： Type 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin （35 mg/kg） and high-fat diet. Four weeks after the confirmation of diabetes, diabetic rats were treated with diosmin （50 and 100 mg/kg, p.o.） for next 4 weeks. Rats were evaluated for biochemical, behavioral and oxidative stress parameters. Eddy＇s hot plate and tail immersion test were performed on 6th, 7th, 8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively. Further, the walking function test was performed for assessing the motor responses at the end of the treatment schedule. RESULTS： Rats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test. Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight, elevated blood sugar and lipid profiles. Further the dose-dependent improvement was observed in thermal hyperalgesia, cold allodynia and walking function in diabetic rats treated with diosmin. Elevated levels of malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment. CONCLUSION： Diosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.     

针刺透穴法对糖尿病周围神经病变神经传导速度的影响：随机对照试验

糖尿病周围神经病变（diabetic peripheral neuropathy,DPN）是糖尿病最常见的慢性并发症和主要的致残因素之一。患者常表现为肢体感觉异常,伴麻木、针刺、灼热或如踏棉垫感,有时伴有痛觉过敏,后期出现肌力减弱以至肌肉萎软和瘫痪,严重影响糖尿病（diabetes mellitus,DM）患者的身心健康和生活质量。国内一项流行病学调查显示DPN占DM所有并发症的16．44％。中医将其归属于消渴病合并“痹证”、“痛证”、“痿证”范畴。目前对于DPN尚无特异性治疗方法,针刺是临床采用的手段之一,本研究探讨了针刺透穴法对DPN神经传导速度的影响。     

Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats

Background Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients.Hyperglycemia markedly increases the risk of cardiovascular disease.Endothelial dysfunction is common in type 2 diabetes mellitus （DM） and is an early indicator of diabetic vascular disease.Therefore,it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium.The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.Methods Forty male Sprague-Dawley rats （age,8 weeks; weight,180-200 g） were included in this study and fed with a normal chow diet for 1 week.Rats （n=10） served as the normal control group （NC group） were fed with a normal chow for another 2 weeks and received an injection of saline.The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups （n=10 rats per group） as follow：type 2 DM group （DM group）,DM ＋ gliquidone group （GLI group） and DM ＋ metformin group （MET group）.Five weeks later,all rats were fasted overnight and taken tail blood samples for biochemical determinations.Then rats in the NC and DM groups were administrated with normal saline,while rats in the MET and GLI groups were administrated with metformin （100 mg/kg） or gliquidone （10 mg/kg）,respectively.All medicines were given via intragastric administration for 8 weeks.After 16 weeks,plasma triglyceride （TG）,total cholesterol （TC）,low density lipoprotein cholesterol （LDL-C）,high density lipoprotein cholesterol （HDL-C） were measured.The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H＆E staining.Results Metformin treatment prevented weight gain （（315.80±52.16） g vs.（318.70±68.48） g,P=0.773）,improved plasma TG,HDL-C and LDL-C levels （P=0.006,0.003,0.001,respectively,all P ＜0.05）.However,gliquidone showed no significant effects on plasma TG and TC levels （P=0.819,0.053,respectively）.LDL-C and HDL-C in the GLI group changed （（0.46±0.10） mmol/L vs.（0.36±0.14） mmol/L,P=0.007; （0.99±0.27） mmol/L vs.（1.11±0.18） mmol/L,P=0.049）.Both metformin and gliquidone treatment lowered blood glucose levels （P=0.001,0.004,respectively,P ＜0.05）.Under light microscopy,no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group.In the DM group,the aortic wall structure was unclear,the intima was thickened with irregular intima,and membrane elastic fibers collapsed.The aortic intima in the MET and GLI groups was smoother compared with the DM group,but the endothelial structure of the MET group was closer to that of the NC group.Conclusions Both metformin and gliquidone have anti-atherosclerotic effects.But the endothelial structure of the MET group was closer to that of the NC group.Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C,whereas gliquidone therapy did not lose weight and decrease serum level of TG.These data may have important implications for the treatment of patients with type 2 DM.     

Chromium-containing traditional Chinese medicine,Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTPIB and PCK2 in diabetic rats

OBJECTIVE： Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of-13anmai Xiaoke （TMXK） Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. METHODS： Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin （50 mg/kg, tail vein）. One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction （qPCR）. Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance （HOMA-IR） index were also measured. RESULTS： The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression （1 752 increased, 471 decreased）. Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were ＂insulin signaling pathway＂, ＂glycolysis/ gluconeogenesis＂ and ＂citrate cycle （-ICA）＂. qPCR showed that relative levels of forkhead box 03 （Fox03）, phosphoenolpyruvate carboxykinase 2 （Pck2）, and protein tyrosine phosphatase 1B （Ptplb） were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 （Aktl） and insulin receptor substrate 2 （Its2） were increased. CONCLUSION： Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.     

Role of polymorphisms of the IGF2 and IGFBP3 genes and risk of gastric carcinoma in China

Background The insulin-like growth factor signaling pathway plays an important role in the modulation of cell growth and proliferation.The aim of this study was to investigate the role of polymorphisms of the insulin-like growth factor 2 （IGF2） and IGF-binding protein 3 （IGFBP3） genes,which encode key proteins of this pathway,as risk factors for gastric carcinoma （GC）.Methods A case-control study including 404 histologically confirmed GC patients and 424 healthy controls of the same ethnicity was conducted to retrospectively investigate the genetic polymorphisms of two genes,IGF2＋820A＞G （rs680） and IGFBP3 A-202C （rs2854744）.Adjusted odds ratios （ORs） and 95％ confidence intervals （C/s） were calculated using Logistic regression.Results The IGF2 genetic variants examined contributed to GC risk individually （OR,1.26; 95％ CI,1.08-1.46）.The genotype frequencies of IGFBP3 A-202C were not significantly different between the cancer cases and controls （P ＞0.05）.Compared to the IGF2 AA genotype,carriers of one variant combined genotype were more pronounced among young subjects （＜60 years）,male subjects,never smokers,and those with a family history of cancer （OR=1.36,95％ CI=1.09-1.72,P ＜0.05; OR=1.61,95％ C/=1.28-2.08,P ＜0.05; OR=1.46,95％ C/=1.11-1.98,P ＜0.05; OR=1.53,95％ C/=0.91-2.6,P ＜0.05; respectively）.Moreover,when the combined effects of the risk genotypes were investigated,significant associations were detected between highrisk genotypes in IGF2 and IGFBP3 （OR,2.47; 95％ CI,1.75-3.49）.Conclusions Our results suggest that polymorphic variants of the IGF2 genes modulate gastric carcinogenesis.Moreover.when the IGF2 and IGFBP3 variants are evaluated toaether,a areater effect on GC risk is observed.     

Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family简

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin（1, 2 and 4 μmol/L） could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.     

Erbin interacts with Sema4C and inhibits Sema4C-induced epithelial-mesenchymal transition in HK2 cells

Erbin, a member of Leucine-rich repeat and PDZ-containing protein family, was found to inhibit TGF-β-induced epithelial-mesenchymal transition （EMT） in our previous study. However, the mechanism of Erbin in regulating EMT is unclear. Semaphorin protein Sema4C, with PDZ binding site at C-terminal has been recognized as a positive regulator of EMT. Here, we aimed to examine the inter- action between Erbin and Sema4C. HK2 cells were treated with TGF-β1, or transfected with Erbin and （or） Sema4C. Interaction of Erbin and Sema4C was identified by immunoprecipitation. RT-PCR was used to detect the expression of Erbin and Sema4C at mRNA level after transfection. The expression levels of Erbin, Sema4C, and markers of EMT were measured by using Western blotting or ELISA. Af- ter HK2 cells were stimulated with 10 ng/mL TGF-β1 for 72 h, the protein expression levels of Erbin and Sema4C were both up-regulated, and immunoprecipitation results showed Erbin interacted with Sema4C in HK2 cells both at endogenous and exogenous levels. Furthermore, overexpression of Sema4C suppressed E-cadherin, induced vimentin and promoted fibronectin secretion, indicating Sema4C promotes the process of EMT. However, HK2 cells overexpressing Erbin were resistant to Sema4C-induced EMT. In contrast, Erbin specific siRNA promoted EMT induced by Sema4C. Taken together, these results suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced EMT.     

Recent advances and findings of angiotensin type 2 receptor: a review

Angiotensinogen is a member of the serpin family. It is produced constitutively and released into the circulation mainly by the liver. Angiotensinogen forms angiotensin Ⅰ by action of the circulated renin released from the kidney. Angiotensin Ⅱ （Ang Ⅱ）, an octapeptide hormone with sequence Asp-Arg-Val-Tyr-Ile-His-Pro-Phe,is converted from angiotensin Ⅰ through removal of two terminal residues by the angiotensin-converting enzyme （ACE） mostly catalyzed in the lung.1 This peptide binds to two subtype receptors, angiotensin type 1 receptor （AT1R） and angiotensin type 2 receptor （AT2R）,members of the superfamily of heptahelical G protein coupled receptors, with different affinities.2 It is well known that AT1R and AT2R crosstalk and lead to counterregulatory functions in many systems, especially the cardiovascular system.3 Accumulating data established the roles of AT1R in the classic actions of Ang Ⅱ including vasoconstriction and cardiovascular hypertrophy, whereas AT2R is suggested to exert direct functions in vasodilation and antigrowth effects.4 Recent publications provide new insights into the roles of AT2R with increasing responsibilities. Recent progresses in AT2R research are reviewed in this article.     

Progress on the M-type phospholipase A2 receptor in idiopathic membranous nephropathy

Objective To highlight current knowledge about M-type phospholipase A2 receptor （PLA2R） which is the first human autoantigen discovered in adult idiopathic membranous nephropathy.Data sources Relevant articles published in English from 2000 to present were selected from PubMed.Searches were made using the terms ＂idiopathic membranous nephropathy,M-type PLA2R and podocyte.＂ Study selection Articles studying the role of M-type PLA2R in idiopathic membranous nephropathy were reviewed.Articles focusing on the discovery,detection and clinical observation of anti-PLA2R antibodies were selected.Results M-type PLA2R is a member of the mannose receptor family of proteins,locating on normal human glomeruli as a transmembrane receptor.The anti-PLA2R in serum samples from MN were primarily IgG4 subclass.Technologies applied to detect anti-PLA2R autoantibody are mainly WB,lIFT,ELISA and so on.Studies from domestic and overseas have identified a strongly relationship between circulating anti-PLA2R levels and disease activity.Conclusion Recent discoveries corresponding to PLA2R facilitate a better understanding on IMN pathogenesis and may provide a new tool to its diagnosis,differential diagnosis,risk evaluation,response monitoring and patient-specific treatment.     

HER2突变非小细胞肺癌患者的临床特征和疗效

1文献来源 Mazieres J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation ： Epidemiologic characteristics and therapeutic perspectives [ J ]. J Clin Oncol, 2013,31 （16） ： 1997- 2003.     

Cyclooxygenase-2 Blockade Inhibits Accumulation and Function of Myeloid-derived Suppressor Cells and Restores T Cell Response after Traumatic Stress

Myeloid-derived suppressor cells （MDSCs） play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 （Cox-2） contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD1 lb＋/Gr-l＋ cells, proliferation and apoptosis of CD4＋ T cells were determined. Ar- ginase activity and arginase-1 （Arg-1） protein expression of splenic CDllb＋/Gr-I＋ cells, and de- layed-type hypersensitivity （DTH） response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD1 lb＋/Gr-l＋ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD1 lb＋/Gr-l＋ ceils. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4＋ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.     

Correlation between magnetic resonance T2 image signal intensity ratio and cell apoptosis in a rabbit spinal cord cervical myelopathy model

Background Cervical spondylotic myelopathy （CSM） is a common cause of disability in elderly patients.Previous studies have shown that spinal cord cell apoptosis due to spinal cord compression plays an important role in the pathology of myelopathy.Although changes in magnetic resonance imaging （MRI） T2 signal intensity ratio （SIR） are considered to be an indicator of CSM,little information is published supporting the correlation between changes in MRI signal and pathological changes.This study aims to testify the correlation between MRI T2 SIR changes and cell apoptosis using a CSM animal model.Methods Forty-eight rabbits were randomly assigned to four groups：one control group and three experimental chronic compression groups,with each group containing 12 animals.Chronic compression of the cervical spinal cord was implemented in the experimental groups by implanting a screw in the C3 vertebra.The control group underwent sham surgery.Experimental groups were observed for 3,6,or 9 months after surgery.MRI T2-weighted SIR Tarlov motor scores and cortical somatosensory-evoked potentials （CSEPs） were periodically monitored.At each time point,rabbits from one group were sacrificed to determine the level of apoptosis by histology （n=6） and Western blotting （n=6）.Results Tarlov motor scores in the compression groups were lower at all time points than the control group scores,with the lowest score at 9 months （P ＜0.001）.Electrophysiological testing showed a significantly prolonged latency in CSEP in the compression groups compared with the control group.All rabbits in the compression groups showed higher MRI T2 SIR in the injury epicenter compared with controls,and higher SIR was also found at 9 months compared with 3 or 6 months.Histological analysis showed significant apoptosis in the spinal cord tissue in the compression groups,but not in the control group.There were significant differences in apoptosis degree over time （P ＜0.001）,with the 9-month group displaying the most severe spinal cord apoptosis.Spearman＇s rank correlation test showed that there was close relation between MRI SIR and degree of caspase-3 expression in Western blotting （r=0.824.P ＜0.001）.Conclusions Clear apoptosis of spinal cord tissue was observed during chronic focal spinal compression.Changes in MRI T2 SIR mav be related to the severity of the apoptosis in cervical spinal cord.     

Heme oxygenase-1 promotes Caco-2 cell proliferation and migration by targeting CTNND1

Background Heme oxygenase-1 （HO-1） can be induced by inflammatory cytokines,oxidation,ischemia,hypoxia,and endotoxins.As a ＂graft survival protective gene,＂ HO-1 is a hot spot in organ transplantation research.However,the role of HO-1 gene expression in the function of human colon adenocarcinoma cell line （Caco-2） cells has not been reported previously.Methods The role of HO-1 in the proliferation and migration of Caco-2 cells was analyzed using a stable HO-1 expression plasmid.We constructed a recombinant adeno-associated virus plasmid containing the HO-1 gene,heme oxygenase 1 （HMOX1）,which was transfected into Caco-2 intestinal cells.We identified a number of target genes by global microarray analysis combined with real-time polymerase chain reaction （PCR） and chromatin immunoprecipitation assay.Results Our results showed that significant HO-1 upregulation was demonstrated in the Caco-2 cells after HO-1 transfection.Restoration of HO-1 expression promoted proliferation and invasion in vitro.The CTNND1 gene,a member of the armadillo protein family,was identified as a direct HO-1 target gene.Conclusion Overexpression of HO-1 promotes Caco-2 cell proliferation and migration by targeting the CTNND1 gene.     

Predicting value of serum soluble ST2 and interleukin-33 for risk stratification and prognosis in patients with acute myocardial infarction

Background Acute myocardial infarction （AMI） is a common cardiac emergency with high mortality.Serum soluble ST2 （sST2） is a new emerging biomarker of cardiac diseases.The present study is to investigate the predictive value of sST2 and interleukin-33 （IL-33） for risk stratification and prognosis in patients with AMI.Methods Fifty-nine patients with AMI,whose chief complaint was chest pain or dyspnea,were selected for our study.Physical examination,chest radiograph,electrocardiograph （ECG）,biomarkers of myocardial infarction,NT-proBNP,echocardiography and other relevant examinations were performed to confirm the diagnosis of AMI.Thirty-six healthy people were chosen as the control group.Serum samples from these subjects （patients within 24 hours after acute attack） were collected and the levels of sST2 and IL-33 were assayed by enzyme-linked immuno-sorbent assay （ELISA） kit.The follow-up was performed on the 7th day,28th day,3rd month and 6th month after acute attack.According to the follow-up results we defined the end of observation as recurrence of AMI or any causes of death.Results Median sST2 level of the control group was 9.38ng/ml and that of AMI patients was 29.06ng/ml.Compared with the control group,sST2 expression in the AMI group was significantly different （P〈0.001）.In contrast,the IL-33 level showed no significant difference between the two groups.Serum sST2 was a predictive factor independent of other variables and may provide complementary information to NT-proBNP or GRACE risk score.IL-33 had no relationship to recurrence of AMI.Both sST2 and the IL-33/sST2 ratio were correlated with the 6-month prognosis; areas under the ROC curve were 0.938 and 0.920 respectively.Conclusions Early in the course （〈24 hours） of AMI,sST2 usually increases markedly.The increase of sST2 has an independent predictive value for the prognosis in AMI patients and provides complementary information to NT-proBNP or GRACE risk score.The IL-33/sST2 ratio correlates with the 6-month prognosis of AMI patients.However,there is no significant relationship between IL-33 and the prognosis of AMI patients.     

Effects of pre-pregnancy body mass index on pregnancy outcomes

Prevalence of overweight and obesity has continued to increase among women of child bearing age all over the world in recent decades. Its impact on short-term and long-term maternal and fetal outcomes continued to grow, such as increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, fetal macrosomia, perinatal mortality and chance for cesarean deliveries） What＇s more, underweight before pregnancy also has some hazardous effects on pregnant women and fetus, such as increased risk of delivering infants small for gestational age and preterm delivery.2 The present study determined the prevalence of each body mass index （BMI） group of an obstetric population of the mainland of China, and effects of the maternal pre-pregnancy BMI on multiple antepartum, intrapartum and neonatal outcomes.     

CHYLORRHEA COMPLICATING D2+a GASTRECTOMY: REVIEW OF THE LITERATURE AND CLARIFICATION OF TERMINOLOGY APROPOS ONE CASE

Lymphatic complications leading to retention,accumulation or drainage of peritoneal fluid are frequently encountered following extended or superextended lymphadenectomy for gastric cancer.1 The vast majority of these drainages usually subsides spontaneously, but in some instances they can persist for long period of time causing significant morbidity.However, the classification,