Objective To investigate changes of serum silent information regulator 1 (Sirt1) and inflammatory cytokines in type 2 diabetes patients with different stages of diabetic nephropathy.To explore the relationship between serum Sirt1 level and inflammatory cytokines in type 2 diabetic patients with different urinary albumin excretion rates.Methods A total of 436 cases with type 2 diabetes were divided into three groups:normoalbuminuric [D1,n =168],microalbuminuric [D2;n =152],and macroalbuminuric [D3,n =116].Serum Sirt1,hypoxia-inducible factor-1α (HIF-1α),early growth response protein 1 (EGR1),insulin-like growth factors-Ⅰ (IGF-Ⅰ),and monocyte chemotactic protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA).Results The levels of serum Sirt1 in type 2 diabetes patients were significantly lower than that in control group,and with the increase of urinary protein excretion rate,the levels of serum Sirt1 in group D1,D2 and D3 were decreased gradually (P ＜ 0.01).Compared to control,serum inflammatory cytokines (HIF-1α,EGR1,IGF-Ⅰ,and MCP-1) levels were significantly increased in type 2 diabetic patients and gradually increased in the patients of D1,D2 and D3 groups (P ＜0.01).Furthermore,Serum Sirt1 was negatively correlated with the levels of inflammatory cytokines.Age,duration,fasting blood glucose (FBG),fasting insulin (FINS),homeostasis model assessment insulin resistance index (HOMA-IR),glycosylated hemoglobin (HbA1c),low density lipoprotein (LDL),total cholesterol (TC),triglyceride (TG),serum creatinine (Scr),blood urea nitrogen (BUN),uric acid (UA),HIF-1α,EGR1,IGF-Ⅰ,and MCP-1 were positively correlated with Ln Koc of urinary albumin to creatinine ratio [Ln(ACR)] (P ＜ 0.05);and Sirt1 were negatively correlated with Ln(ACR)(P ＜ 0.01).HIF-1α,MCP-1,IGF-Ⅰ,duration,BUN,Sirt1,UA,LDL,and EGR1 were independent factors that significantly influenced Ln (ACR) (P ＜ 0.05).Conclusions Serum Sirt1 might be a new target for the treatment of diabetic nephropathy.Enhancing serum Sirt1 levels might have a role in delaying the progression of diabetic nephropathy.

Seven-year-program medical education is an important model to train high-level medical person.Through the change of the teaching concept in medicine cytobiology experiment,re-form of the teaching content,and the use of a variety of effective teaching methods,students’com-prehensive quality,innovative thinking and practical ability is improved,which can meet the needs of modern medical education.

By participating in the research practice of basic medicine,the innovative consciousness,the scientific thinking and researching ability of seven-year program medical students can be improved. Meanwhile,the generalization of Open Experimental Teaching and further development of self-design experiment also improve the innovation and research ability of medical students,which can serve as a new approach to the quality education of higher medical talents.

Objective To explore the roles of biomarkers of the ratios of microRNA (miRNA)in osteosarcoma.Methods The blood samples from 20 patients with osteosarcoma and 30 healthy people with similar age were choosed.The miRNA expression profiles were filtered by gene chips of high flux.The results were verified by qRT-PCR.The miRNA expression ratio was analysed by receiver operating characteristic (ROC)curve aiming to find the most predictive potential combination-type markers.Results Two hundred and fifty-eight miRNAs were found to be significantly deregulated in blood samples from 30 patients with osteo-sarcoma as compared with their matching normal blood samples (F=5.564,P<0.05).Four miRNAs were choosed from blood samples of22 patients with osteosarcoma and normal blood samples.MiR-181b,miR-199b-5p and miR-451 were significantly higher than that in normal blood sample (F=6.283,P<0.05),while miR-124 showed low expression (F=7.201,P<0.05).Furthermore,the ratio of miR-199b-5p/miR-124 showed a high sensitivity (96%)and specificity (97%).Conclusion The abnormal expression of miRNA in osteosar-coma makes it have a predictive effect.The ratio of miR-199b-5p/miR-124 could be served as combination-type biomarkers in the diagnosis of osteosarcoma.

Bonetumorisonekindofmalignanttumorwhichthreatslifeamongchildrenandadoles-cent.Osteosarcoma (OS ) and Ewing sarcoma (ES ) have been paid much attention by medical community because of their complex occurrence,development,metastasis mechanism and poor prognosis.The research showed that activation of protooncogene and mutation of suppressor gene,absence of apoptosis signal and hypox-ia-inducible factor (HIF)all participated in the occurrence,development and metastasis of OS and ES.It is suggested that clarified pathomechanism of bone tumors could provide more effective therapeutic strategies and lower the mortality of patients.

Objective To observe the availability and safety of ventricular septal defect (VSD) occluder in infants and young children with large patent ductus arteriosus (PDA) associated with severe pulmonary hypertension.Methods Five patients (1 male and 4 fomale) of large PDA aged 5 months to 3 years,weighted from 5.1 to 15 kg,body surface area (BSA) 0.37-0.58 m2 underwent transcathter intervention with concentric VSD occluders from June 2008 to May 2009.Arterial ducta were tube-like and their diameters were 5.7 to 8.5 mm,with ulmonary vascular resistance from 4.8 to 5.7 Wood Unit,Qp/Qs 3.4-4.6.Three patients were given Bosentan after intervention.Results The large PDAs were successfully closed with VSD occluders,including 1 concentric perimembranous VSD occluder and 4 muscular VSD occluders.They all discharged 4 to 5 days with hidrosis and weight improved.Echocardiogram indicated VSD occluder was stable,no residue shunt and no stricture of left pulmonary artery and descending aorta were found.According to tricuspid and pulmonary regurgitation,pulmonary arterial pressure decreased differently and returned to normal after 6 months follow-up.Conclusion VSD occluder is available and effective to close large PDA associated with severe pulmonary hypertension in inrants and young children,but more cases and long-term follow-up are necessary.

Objective To explore the associations of serum Mir-217 with silent information regulator 1 (Sirt1)and hypoxia-inducible factor-1α(HIF-1α)in type 2 diabetic patients with different urinary albumin excretion rates. Methods A total of 479 patients with type 2 diabetes were divided into normoalbuminuric(D1, n=181), microalbuminuric(D2, n=165), and macroalbuminuric(D3, n=133)subgroups. 192 normal subjects served as control group. Serum level of Mir-217 was detected by realtime PCR. Serum Sirt1, HIF-1α, and vascular endothelial growth factor ( VEGF ) levels were determined by enzyme-linked immunosorbent assay. Results Compared with control subjects, serum Mir-217 level was significantly increased in type 2 diabetic patients and gradually increased in D1, D2, and D3 groups(P<0. 01). The parameters of age, diabetes duration, body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistant index(HOMA-IR), HbA1C, low density lipoprotein-cholesterol( LDL-C) , total cholesterol ( TC ) , triglyceride ( TG ) , serum uric acid ( SUA ) , blood urea nitrogen(BUN), HIF-1α, VEGF, and Mir-217 all were positively correlated with ACR(all P<0. 05). High density lipoprotein-cholesterol(HDL-C)and Sirt1 were negatively correlated with ACR(both P<0. 05). VEGF, HIF-1α, Mir-217, BUN, diabetes duration, LDL-C, Sirt1, and SUA were independent factors that influenced ACR(all P<0. 01). Additionally, diabetes duration, HOMA-IR, HbA1C, ACR, LDL-C, TC, TG, SUA, BUN, HIF-1α, and VEGF were positively correlated with Mir-217(all P<0. 05), while Sirt1 was negatively correlated with Mir-217(P<0. 01). Conclusion Serum Mir-217, as a possible biomarker for early diagnosis of diabetic nephropathy, may be involved in the development of diabetic nephropathy by promoting chronic inflammatory reaction, renal fibrosis, and angiogenesis.

267 newly-diagnosed patients with type 2 diabetes were divided into normoalbuminuria group [group N-UAlb, urinary albumin to creatinine ratio (UACR)<30 mg/g, n=103], microalbuminuria group(group M-UAlb, UACR 30~300 mg/g, n=88 ) , and macroalbuminuria group ( group L-UAlb, UACR>300 mg/g, n=76). The control group(group NC) consisted of 114 healthy individuals. Serum betatrophin, adiponectin(APN), and interleukin-1β( IL-1β) levels were determined with ELISA methods and the parameters of body mass index (BMI), estimated glomerular filtration rate(eGFR), HbA1C, fasting plasma glucose(FPG), OGTT 2h plasma glucose(2hPG), fasting insulin(FINS), OGTT 2h postprandial insulin(2hPINS), fasting C-peptide(FCP), homeostasis model assessment insulin resistant index(HOMA-IR), and blood lipid were collected. Compared with group NC, the serum betatrophin levels in patients with type 2 diabetes were obviously increased. In patients with type 2 diabetes, betatrophin levels increased along with the increase of UACR and there were significant differences in betatrophin among the three groups(P<0. 01). Betatrophin positively correlated with UACR, HbA1C, FPG, 2hPG, FINS, 2hPINS, HOMA-IR, TC, LDL-C, and TG( r were 0. 785, 0. 225, 0. 136, 0. 241, 0. 386, 0. 223, 0. 411, 0.216,0.193,and0.298,allP<0.05),and betatrophin were also positively correlated with APN and IL-1β(rwere 0. 643 and 0. 710, both P<0. 01). Stepwise multiple regression analysis showed that UACR, HbA1C, FINS, and TG were independent relevant factors affecting betatrophin levels.

Objective To investigate the expression levels of serum vasohibin-1(VASH-1)in type 2 diabetes mellitus(T2DM)patients at different stages of urinary albumin to creatinineratio(UACR)and to attempt to investigate the relationship between VASH-1 and inflammation and fibrosis in the pathogenesis of diabetic nephropathy(DN), one of the microvascular complications of T2DM. Methods 486 patients with T2DMwere divided into four groups:normal albuminuria [ UACR<30 mg/ g, n = 134], microalbuminuria [ UACR at 30-300 mg/ g, n = 122], clinical albuminuria [UACR > 300 mg/ g, n = 106 ], and clinical albuminuria hypertensive [ UACR > 300 mg/ g, with hypertension, n=124] groups. Age, course, serum levels ofVASH1, inflammation markers(CRP, ESR)and fibrosis marker( TGF-β1) with other biochemical indicators were measured, and 130 normal control subjects were also included. Results Compared with normal control group, the levels of UACR, HbA1C ,ESR, CRP, TGF-β1 and VASH-1 in groups ofnormal albuminuria, microalbuminuria, clinical albuminuria, and clinical albuminuria hypertensive were significantly higher(P<0. 05). Pearson correlation analysis showed that levels of VASH-1 were positively correlated with UACR, HbA1C ,ESR, CRPand TGF-β1( r = 0. 521, 0. 261, 0. 519, 0. 523, 0. 479, P<0. 001), while multivariate regression analysis showed that levels of UACR, HbA1C ,ESR, CRP and TGF-β1 were important factors affecting serum VASH-1 levels. Conclusion Serum levels of VASH-1 may become new biomarkers of early diagnosis of DN. Consequently, VASH-1 level may provide a new pattern and direction of inflammation and fibrosis for consideration in diabetic kidney damage.

Objective To investigate the association of adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)with urinary albumin excretion rate in patients with type 2 diabetes mellitus (T2DM),and to explore the role of APPL1 in the development of diabetic kidney disease(DKD). Methods According to the urinary albumin/creatinine ratio(UACR),288 newly-diagnozed patients with T2DM were divided into normal albuminuria group(UACR<30 mg/g,n=116),microalbuminuria group(UACR 30 ~300 mg/g,n=95),and macroalbuminuria group(UACR>300 mg/g,n=77). 130 healthy subjects with matched sex and age were used as control group. Serum APPL1,tumor necrosis factor α(TNF-α),and adiponectin levels were measured by ELISA method. Results Serum APPL1 level in T2DM patients was significantly higher than that in control subjects (P<0.01), and increased with the rising of UACR. In patients with T2DM, serum APPL1 level was negatively correlated with estimated glomerular filtration rate(r=-0.246, P<0.01) while it was positively correlated with HbA1C, low density lipoprotein cholesterol, total cholesterol, triglycerides, insulin resistance index, serum creatinine,blood urea nitrogen, systolic blood pressure, TNF-α, and adiponectin(r=0. 119, 0. 167, 0. 209, 0.194,0.273,0.242,0.131,0.144,0.365, and 0.952, respectively, P<0.05 or P<0.01). Conclusion Serum APPL1 level in patients with T2DM was increased with the rising of UACR, suggesting that APPL1 may be involved in the development of DKD.