2008年 · 第121卷第21期

2008 is destined to be memorable for all:commences with unexpected early release of blood glucose-lowering,arm of ACCORD study on Chinese New Year's Eve,1 and then successful failure of intensive glycemic control of ADVANCE,2 disappointed results of VADT and HEART2D trials in succession,ends with reports of 20-year follow-up of UKPDS study,3 the climax of 2008 chapter。

Abstract：Background Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions.However,the evaluation of beta cell functions is either expensive or inconvenient for clinical practice.We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.Methods A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis.The early insulinogenic index (△I30/△G30),the area under the curve of insulin (AUC-I),and homeostasis model assessment were applied to evaluate the early phase secretion,total insulin secretion,and insulin resistance respectively.Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.Results The △I30/△G30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG.At the FPG of 110 mg/dl (a pre-diabetic stage),the △I30/△G30 lost 50% of its maximum while the AUC-I was still at a compensated normal level.The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes),while the △I30/△G30 almost remained at 25% of its maximum value.When hyperglycemia continuously existed at >180 mg/dl,beth the △I30/△G30 and AUC-I were totally lost.Conclusion The increased fasting plasma glucose reflects progressive decompensation of beta cell functions,and could be used to guide the strategy of clinical treatments。

Abstract：Background Retinol binding protein 4 (RBP4),as an adipocyte secreted cytokine,was recently found to be inversely correlated with expression of glucose transporter 4 (GLUT4) in insulin resistance (IR) state and to have an intimate relationship with IR and type 2 diabetes mellitus (T2DM).The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde (tin),berberine (Bet),and metformin (Met) as well as their impacts on the RBP4-GLUT4 system.Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction.Rats were divided into five groups:the control group,the diabetes group,the diabetes+Ber group,the diabetes+Cin group,and the diabetes+Met group.Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels.Results After treatment for four weeks,both Cin and Ber displayed significant hypolipidemic,hypoglycemic,and insulin sensitizing functions (P<0.01) compared with the control group.Their effects on lowering fasting plasma glucose (FPG),low density lipoprotein-cholesterol (LDL-C) and homeostasis model assessment of insulin resistance (HOMA-IR) seem even better than that of Met.Cin and Bet markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein,and Cin seemed more notable in affecting these two proteins.Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes.Their mechanisms involve the RBP4-GLUT4 system,during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated。

Abstract：Background Currently,there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects.Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors (ACEIs) on the reduction of blood pressure and the protection of target organs,the clinical application of this kind of drugs is very widespread.However,it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs'postischemic revascularization.It is of major therapeutic importance to resolve these questions.This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia,the role and related molecular mechanisms of ACEI in postischemic revascularization.Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision.Diabetic rats were randomly allocated to one of the following treatments for 4 weeks:ACEI by perindopril;perindopril in combination with a nitric oxide synthase (NOS) inhibitor;perindopril in combination with bradykinin (BK)-B1 receptor (B1R) antagonist or saline.The differences of angiogenesis,the mRNA and protein expression of endothelial nitric oxide synthase (eNOS),vascular endothelial growth factor (VEGF) and basic fibroblast (bFGF),constitutive nitric oxide synthase (cNOS) activity and nitric oxide (NO) content were observed after treatment.Results In non-ischemic hind limbs,no significant changes in capillary density,or the mRNA and protein expression of eNOS,VEGF and bFGF,or the NO content and the cNOS activity were observed among all groups.On the contrary,in ischemic hind limbs,the capillary density in diabetic rats decreased by 27% when compared with the control rats,so did the mRNA and protein expression of eNOS,VEGF and bFGF,or the NO content and the cNOS activity (P<0.05).The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to untreared diabetic rats.Moreover,administration of perindopril enhanced the mRNA expression of eNOS,VEGF,and bFGF by 1.45-,1.44-,and 1.33-fold,increased the protein content of the above indices by 1.55-,1.30-and 1.50-fold compared with the untreated diabetic rats respectively.Perindopril also increased NO content and cNOS activity to 1.33-and 1.38-fold of that in untreated diabetic rats.The combination of BK-B1R antagonist significantly decreased the above indices (P<0.05).In contrast,the combination of NOS inhibitor decreased the expression of eNOS and bFGF,the NO content and the cNOS activity,while the expression of VEGF did not change.Conclusions Diabetes mellitus reduces the neovascularization,related growth factors expression and activity in the diabetic rat ischemic legs model.Treatment of perindopril improves postischemic revascularization.This effect is mediated,at least in part,by the BK-B1R-related pathway,and the activation of VEGF/eNOS/bFGF signals may be involved in the pro-angiogenic effect。

Abstract：Background Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated,its role in cardioprotection remains largely unknown.This study aimed to determine the effects of GLP-1 on injury of rats cardiac myocytes induced by hypoxia-reoxygenation (H/R) and the possible mechanisms.Methods The cultured neonatal rats cardiac myocytes were randomly divided into seven groups:the normal control group,the H/R group,the GLP-1+H/R group,the GLP-1+H/R+UO126 (the p42/44 mitogen-activated protein kinase (MAPK) inhibitor) group,the GLP-1+H/R+LY294002 (phosphatidylinositol 3-kinase (P13K) inhibitor) group,the H/R+UO126 group,and the H/R+LY294002 group.The lactate dehydrogenase (LDH) activity,apoptosis rate of cardiac myocytes,and caspase-3 activity were detected after the injury of H/R.Results Compared with the normal control group,the activity of LDH,cardiac myocyte apoptosis rate,and caspase-3 activity all increased significantly in the H/R group (P<0.01).Compared with the H/R group,these three indices all decreased in the H/R+GLP-1 group (P<0.01).However,the changes of LDH activity,apoptosis rate,and caspase-3 activity were inhibited by LY294002 and UO126 respectively.Conclusions GLP-1 can directly act on cardiac myocytes and protect them from H/R injury mainly by inhibiting their apoptosis.Its mechanism may be through the P13K-Akt pathway and the MAPK signaling pathway。

Abstract：Background The value of intravascular ultrasound (IVUS) imaging in patients with replacement of the ascending aorta for acute type A aortic dissection (AD) is unknown.The purpose of this study was to assess the potential use of IVUS imaging in this setting.Methods From September 2002 to July 2005,IVUS imaging with a 9 MHz probe was performed in a series of 16 consecutive patients with suspected or established AD.This study focused on 5 of them with replacement of the ascending aorta for acute type A AD.Among these 5 patients,other imaging modalities including aortography,spiral computed tomography,magnetic resonance imaging and transesophageal echocardiography were performed in 5,3,3 and 1 patients,respectively.Results There were no complications related to IVUS imaging.For the replaced graft,as other imaging modalities,IVUS could identify all 5 grafts,the proximal and the distal anastomoses,and the ostia of the reimplanted coronary arteries.In 2 cases,IVUS detected 2 peri-graft pseudo-aneurysms (1 per case),which were also detected by magnetic resonance imaging but omitted by aortography.For the residual dissection,IVUS had similar findings as other imaging modalities in detecting the patency (5/5),the longitudinal and the circumferential extent,the thrombus (4/5),the recurrent dissection (1/5) and an aneurysm distal to the graft (5 in 4 patients).However,it detected more intimal tears and side branch involvements than other imaging modalities (15 vs 10 and 3 vs 1,respectively).Conclusions In following-up patients with replacement of the ascending aorta for acute type A AD,IVUS imaging can provide complete information of the replaced graft and the residual dissection.So,IVUS imaging may be considered when the four current frequently used imaging modalities can not supply sufficient information or there are some discrepancies between them。

Abstract：Background Randomized clinical trials have demonstrated equivalent safety to bare-metal stents after drug-eluting stents (DES) implantation.However,the DES thrombosis in randomized trials could not be comparable to those observed in clinical practice,frequently including off-label indications.This study sought to assess the incidence of DES thrombosis after implantation of DES in patients with real world coronary artery disease (CAD) in China.Methods From December 2001 to April 2007,8190 consecutive patients received the treatment with DES,5412 patients completed one year follow-up:2210 with sirolimus-eluting stent Cypher,1238 with paclitaxel-eluting stent Taxus and 1964 with Chinese sirolimus-eluting stent Firebird.After two years of follow-up,there were 2176 patients (1245 Cypher,558 Taxus and 373 Firebird).All patients were treated with aspirin and clopidogrel over at least 9 months.Results Among 8190 patients,17 patients had acute stent thrombosis (0.24%):7 in the Cypher group,4 Taxus and 6 Firebird;23 patients had subacute stent thrombosis:8 Cypher,6 Taxus and 9 Firebird.The incidence of acute and subacute thrombosis was 0.49%:0.50% Cypher,0.63% Taxus and 0.41% Firebird.The incidence of late thrombosis at one year followup was 0.63%:0.63% Cypher,0.88% Taxus and 0.46% Firebird;at two year follow-up the incidence was 0.74%:0.72% Cypher,0.90% Taxus and 0.54% Firebird.There was no significant difference among three groups at 1 year and 2 years follow-up.Conclusion The first generation DES in the treatment of complex lesions are safe and effective if patients are aggressively treated with dual antiplatelet agents。

Abstract：Background Microendoscopic discectomy (MED) is a minimally invasive operation that allows rapid recovery from surgery for lumbar disc herniation,but has replaced traditional open surgery in few hospitals because most surgeons avoid its long learning curve.We evaluated the effectiveness and safety of lumbar MED at stages of spinal surgeons'learning curve.Methods Fifty patients receiving MED from June 2002 to February 2003 were divided into chronological groups of ten each:A-E.The control group F was ten MED patients treated later by the same medical team (September-October 2006).All operations were performed by the same team of spinal surgeons with no MED experience before June 2002.We compared groups by operation time,blood loss,complications and need for open surgery after MED failure.Results Operation times by group were:A,(107±14) minutes;B,(85±13) minutes;C,(55±19) minutes;D,(52±12) minutes;E,(51±13) minutes;and F,(49±15) minutes.Blood loss were:A,(131±73) ml;B,(75±20) ml;C,(48±16) ml;D,(44±17) ml;E,(45±18) ml;and F,(45±16) ml.Both operation time and blood loss in groups C,D,E and F were smaller and more stable compared with groups A and B.Japanese Orthopedic Association assessment (JOA) score of each group in improvement rate immediately and one year after operation were as follows (in percentage):A,(79.8±8.8)/(89.8±7.7);B,(78.6±8.5)/(88.5±7.8);C,(80.8±11.3)/(90.8±6.7);D,(77.7±11.4)/(88.9±9.3);E,(84.0±8.7)/(89.6±9.0);and F,(77.8±11.6)/(86.9±8.4).Groups showed no statistical difference in improvement rates.Complications developed in three patients in group A,two in group B,and none in the other groups.Conclusions Spinal surgeons performing MED become proficient after 10-20 operations,when their skill becomes fairly sophisticated.Patients' improvement rate is the same regardless of surgeons' phase of learning curve。

Abstract：Background Ciliary body tumors are usually difficult to diagnose and treat in early stages.However,treatment of such tumors has trended toward ocular conservation instead of enucleation.Local excision of ciliary body tumors has become effective with the development of the modern vitrectomy,but long-term outcomes are still not clear.Therefore,we reported the outcome of locally excised ciliary body tumors after long-term follow-up.Methods Twenty-two patients (22 eyes),who had been diagnosed with ciliary body tumors in Beijing Tongren Hospital from January 1996 to June 2001,were enrolled in this prospective cohort study.Localized lamellar sclera-ciliary excisions were performed.In some cases,vitrectomies,scleral graft transplantations,and further excisions of the anterior choroid were performed.Diagnoses were confirmed by histopathologic examination.Patients were followed from five to eleven years after surgery.Their visual acuity,intraocular pressure and local recurrence were recorded with descriptive percentages.Results After surgery,all patients maintained normal eyeball appearances.Six patients maintained circular pupils.The final best corrected visual acuities (BCVA) varied from 0.02-1.00,including 18 patients (81.82%) who had BCVA equal to or better than that before surgery.Fifteen patients (68.18%) had BCVA better than 0.3.Only two patients had intraocular pressure (IOP) of less than 10 mmHg and the other patients maintained normal IOP.Nine cases (40.91%) were given confirmed diagnosis of malignant melanoma,four (18.18%) of melanocytoma,six (27.27%) of nonpigmented ciliary epithelial adenoma,two (9.09%) of neurofibroma,and one (4.55%) of neurinoma.Twenty patients (90.91%) had no recurrence during the follow-up period.In one case melanocytoma recurred seven years after surgery and enucleation was performed.One patient,whose operation removed a malignant melanoma with a diameter of 16 mm,died of hepatic metastasis five years after the operation.Conclusion For some ciliary body tumors,especially in the early stages,local excision is an effective and safe method to save the vision and the eyeball。

Abstract：Background Vascular access (VA) dysfunction is a major clinical complication in the hemodialysis population and has a direct effect on dialysis outcome.This study was conducted to explore the role of microinflammation in the VA dysfunction in maintenance hemodialysis patients.Methods Forty-seven patients (male 35 and female 12) receiving maintenance hemodialysis were included for this study.They were divided into three groups:group 1 (n=15),patients with initial hemodialysis and new arteriovenous fistula (AVF);group 2 (n=18),patients treated with hemodialysis for long term with well-functional VA;group 3 (n=14),maintenance hemodialysis patients with VA dysfunction.Biochemical parameters and serum tumor necrosis factor-a (TNF-a),interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were determined.High-sensitivity C-reactive protein (hs-CRP) was determined by latex-enhanced immuno-nephelometric method.Tissues of radial artery were taken from group 1 and group 3 for the histological study.Expression of CD68 and MCP-1 in the radial artery was determined by immunohistochemistry.Results Serum hs-CRP in group 3 was significantly higher than those in group 1 and group 2 ((7.40±2.42) mg/L vs (4.21±1.62) mg/L and (5.04±3.65) mg/L,P<0.01 and P<0.05,respectively).Serum TNF-a in group 3 was significantly higher than those in group 1 and group 2 ((64.03±9.29) pg/ml vs (54.69±12.39) pg/ml and (54.05±7.68) pg/ml,P<0.05 and P<0.01,respectively).Serum IL-6 in group 3 was also significantly higher than those in group 1 and group 2 ((70.09±14.53) pg/ml vs (56.43±10.11) pg/ml and (60.77±9.70) pg/ml,P<0.01 and P<0.05,respectively).Patients in group 3 had a thicker internal layer of vessels than in group 1 ((0.356±0.056) mm vs (0.111±0.021) mm,P<0.01).Expression of CD68 and MCP-1 in the fistula vessel walls in group 3 were much higher than those in group 1 (P<0.01).Moreover,serum hs-CRP level was positively correlated with the neointimal hyperplasia,the expression of CD68 andMCP-1 in fistula vessel (P<0.01,respectively).Conclusion Microinflammaton might be involved in the dysfunction of AVF in patients with maintenance hemodialysis。

Abstract：Background The human metapneumovirus (hMPV) is a newly discovered respiratory viral pathogen that was first isolated in 2001 in the Netherlands.Its global distribution and long history of infection in humans have been well documented.In this study,we assessed the seropositivity of hMPV IgG antibodies in children in Chongqing,China.Methods The specificity of the enzyme linked immunosorbent assay (ELISA) was first validated by using respiratory syncytial virus (RSV) infected,antigen subtracted reference serum and by performing western blotting using anti-hMPV animal serum.This assay was used to determine the presence of the IgG antibody against hMPV and RSV in 325 serum samples obtained from children aged 0-6 years.Results No crossreaction was detected by ELISA between the antibodies to hMPV and RSV.The seropositivity of the anti-hMPV IgG antibody was 74.5% in children aged 0 to 5 months,64.0% in 6 to 11 months,72.7% in 12 to 23 months,87.1% in 24 to 35 months and 90.3% in 3 to 6 years.Conclusions hMPV is a common and significant respiratory pathogen in Chinese children.Almost all individuals are exposed to hMPV by age 6 years。

Abstract：Background Survivin is a rather specific gene in tumor tissue.We transfected dendritic cells (DCs) with recombinant adenovirus (Ad) containing survivin gene and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene and tested the inducing effect of the transfected DCs on cytotoxic T lymphocytes (CTL) to kill leukemic cells.Methods After derived from the peripheral,DCs was assayed by mixed leukocyte reaction (MLR) tests.Lactate dehydrogenase (LDH) release test was used to evaluate cytotoxicity of CTL.Results Expression of survivin in transfected DCs was confirmed by Western blotting analysis.GM-CSF expression was confirmed by enzyme-linked immunosorbent assay (ELISA).In MLR assay,DCs coinfected with Ad-survivin and Ad-GM-CSF induced higher allogeneic lymphocyte reaction than control DCs at ratios of 1:5,1:10,1:50 and 1:100.DCs coinfected with Ad-survivin and Ad-GM-CSF had much higher activity of CTL to HL-60 cells than DCs infected with Ad-survivin only,Ad-GM-CSF only,or control DCs.Levels of interleukin-12 (IL-12) and interferon gamma (IFN-y) in lymphocyte supernatants containing DCs coinfected with Ad-survivin and Ad-GM-CSF were significantly higher than those in the control group.Conclusion DCs coinfected with Ad-survivin and Ad-GM-CSF induce much higher anti-leukemic response in vitro than those infected with either factor.Therefore,adenovirus vectors containing survivin and GM-CSF genes may be promising vaccine candidates for leukemia therapy。

Abstract：Background A liver support therapy,named molecular adsorbents recirculating system (MARS),has been used for more than 700 liver failure patients in China.We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure.Methods This report analyzed data of 252 patients (mean age (44.9±12.7) years) in three groups:acute severe hepatitis (ASH),subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH).The largest group was CSH (156 patients,61.9%),and 188 patients (74.6%,188/252) were infected with HBV.Results MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins.Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP).There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale.Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%.Survival within the ASH and SSH groups were 81.2% and 75.0%,respectively.In the CSH group,end stage patients were predominant (65/151,43%),whereas the early and middle stage patients had a better prognosis:early stage survival,including orthotopic liver transplantation (OLT) survival of 91.7%,middle stage survival of 75%,end stage survival of 33.8%.Conclusions MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions,including the majority of hepatitis B related liver failure conditions.The appropriate application of MARS for the right indications and stage of hepatic failure,as well as the fulfillment of prescribed treatments,will lead to the optimal therapeutic result。

The study of ancient Greece is essential for the proper understanding of the evolution of modem Western medicine.An important innovation of classical Greek medicine was the development of a body of medical theory associated with natural philosophy,i.e.a strong secular tradition of free enquiry,or what would now be called "science" (Επιστημη).Medical education rests upon the ancient Greek foundations and its history remains a fascinating topic for modem physicians and medical teachers。

Tumor at the site of total hip arthroplasty (THA) is a rare event.There have been 46 cases of malignant tumors at the site of total hip prosthesis since 1974.Among them,there were 41 sarcomas,4 lymphomas and 1 epidermoid.Malignant fibrous histiocytoma was the most common (20 cases) followed by osteosarcoma (9 cases).Here we report a case of a giant cell tumor combined with an aneurysmal bone cyst 3 years after an aluminum oxide ceramic THA。