Volume 121  ·   Issue 09  ·  2008

Abstract：Background Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's disease (AD).Mitochondrial dysfunction has been implicated in this process of neuronal cell death. One promising approach for preventing AD is based upon anti-apoptosis to decrease death of nerve cells. In this study, we observed the memory improving properties of curcumin in mice and investigated the neuroprotective effect of curcumin in vitro and in vivo.Methods The mice were given AlCl3 orally and injections of D-galactose intraperitoneally for 90 days to establish the AD animal model. From day 45, the curcumin group was treated with curcumin for 45 days. Subsequently, the step-through test, neuropathological changes in the hippocampus and the expression of Bax and Bcl-2 were carried out to evaluate the effect of curcumin on the AD model mice. In cultured PC12 cells, AlCl3 exposure induced apoptosis. The MTT assay was used to measure cell viabilities; flow cytometric analysis to survey the rate of cell apoptosis; DNA-binding fluorochrome Hoechst 33258 to observe nuclei changes in apoptotic cells and Western blot analysis of Bax, Bcl-2 to investigate the mechanisms by which curcumin protects cells from toxicity.Results Curcumin significantly improved the memory ability of AD mice in the step-through test, as indicated by the reduced number of step-through errors (P <0.05) and prolonged step-through latency (P <0.05). Curcumin also attenuated the neuropathological changes in the hippocampus and inhibited apoptosis accompanied by an increase in Bcl-2 level (P <0.05), but the activity of Bax did not change (P >0.05). AlCl3 significantly reduced the viability of PC12 cells (P <0.01). Curcumin increased cell viability in the presence of AlCl3 (P <0.01). The rate of apoptosis decreased significantly in the curcumin group (P <0.05) when measured by flow cytometric analysis. Curcumin protected cells by increasing Bcl-2 level (P<0.05), but the level of Bax did not change (P >0.05).Conclusions This study demonstrates that curcumin improves the memory ability of AD mice and inhibits apoptosis in cultured PC12 cells induced by AlCl3. Its mechanism may involve enhancing the level of Bcl-2。

Abstract：Background A model of simulated Alzheimer's disease (AD) induced by aggregated amyloid protein (Aβ1-40) was built in Wister rats to observe the behavioral and pathological changes of Aβ1-40 and the effect of hypodermic insulin injected on the function of study and memory and the expression of Aβ1-40 from the CA1 area of the hippocampus.Methods Experimental groups were as follows: contrast, simulated AD model, contrast of Nacl, and insulin treated. The simulated AD modet was built by microinjection of aggregated Aβ1-40 at the CA1 area of the hippocampus, and was hypodermically injected with 0.9% NaCI (1 ml/kg) and insulin (0.1 U/kg) separately the next day. Two weeks after the modeling, the four groups were tested with water maze about the study and memory function of rats. Three weeks after the injection, the expression of Aβ1-40 at the CA1 area of the hippocampus was examined by pathological tests (HE,Congo red) and immunohistochemical methods.Results The study and memory abilities of rats were ameliorated significantly by the place navigation test and the spatial probe test after the application of insulin. Insulin could decrease the expression of Aβ1-40 at the CA1 area of the hippocampus to reduce the pathological damage of Aβ1-40 to the hippocampal area of rats.Conclusions The injection of aggregated Aβ1-40 to the hippocampal area could simulate the behavioral and pathological features of AD such as the difficulty of study and memory and the damage to neurons. Insulin is effective to improve the function of study and memory and amend the pathological damage of simulated AD model rats. The results give a experimental proof of insulin in the clinical treatment of AD。

Abstract：Background Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.Methods Purified human thioredoxin was injected into adult Wister rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondia by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling ('rUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.Results Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P<0.01), notable reduction of myocyte apoptosis (P <0.01), lower systemic oxidative stress level (P <0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P<0.05),and inhibited the activity of caspase-9 (P <0.05) and caspase-3 (P <0.01 in mRNA and P <0.05 at protein level).Meanwhile, human thioredoxin markedly increased bcl-2 expression (P <0.05).Conclusions These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway。

Abstract：Background Pancreatic islet cell transplantation is an effective approach to treat type 1 diabetes. However, this therapy is not widely used because of the severe shortage of transplantable donor islets. This study investigated whether mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) could be transdifferentiated into insulin producing cells in vitro and the role of extracellular matrix (ECM) gel in this procedure.Methods Human UCB samples were collected and MSCs were isolated. MSCs specific marker proteins were analyzed by a flow cytometer. The capacities of osteoblast and adipocyte to differentiate were tested. Differentiation into islet like cell was induced by a 15-day protocol with or without ECM gel. Pancreatic characteristics were evaluated with immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Insulin content and release in response to glucose stimulation were detected with chemiluminescent immunoassay system.Results Sixteen MSCs were isolated from 42 term human UCB units (38%). Human UCB-MSCs expressed MSCs specific markers and could be induced in vitro into osteoblast and adipocyte. Islet like cell clusters appeared about 9 days after pancreatic differentiation in the inducing system with ECM gel. The insulin positive cells accounted for (25.2±3.4)% of the induced cells. The induced cells expressed islet related genes and hormones, but were not very responsive to glucose challenge. When MSCs were induced without ECM gel, clusters formation and secretion of functional islet proteins could not be observed.Conclusions Human UCB-MSCs can differentiate into islet like cells in vitro and ECM gel plays an important role in pancreatic endocrine cell maturation and formation of three dimensional structures。

Abstract：Background Most liver resections require clamping of the hepatic pedicle (Pringle maneuver) to avoid excessive blood loss. But Pringle maneuver can not control backflow bleeding of hepatic vein, Resection of liver tumors involving hepatic veins may cause massive hemorrhage or air embolism from the injuries of the hepatic veins. Although total hepatic vascular exclusion can prevent bleeding of the hepatic veins effectively, it also may result in systemic hemodynamic disturbance because of the inferior vena cava being clamped. Hepatic venous occlusion, a new technique, can control the inflow and outflow of the liver without clamping the vena cava.Methods A total of 71 cases of liver tumors underwent resection with occlusion of more than one of the main hepatic veins. All tumors involved the second porta hepatis and at least one main hepatic vein. Ligation or occlusion with serrefines, tourniquets and auricular clamps were used in hepatic venous occlusion.Results Of the 71 patients, ligation of the hepatic veins was used in 28 cases, occlusion with a tourniquet in 26, and occlusion with a serrefine in 17. Right hepatic veins were occluded in 38 cases, both right and middle hepatic veins in 2,the common trunk of the left and middle hepatic veins in 24, branches of the left and middle hepatic veins in 2, and all three hepatic veins in 5. Thirty-five cases underwent hemihepatic vascular occlusion, 4 alternate hemihepatic vascular occlusion, 23 portal triad clamping plus selective hepatic vein occlusion, and 9 portal triad clamping plus total hepatic vein occlusion. The third porta hepatis was isolated in 26 cases. The amount of intraoperative blood loss averaged (540±283) (range 100 to 1000) ml in the group of total hemihepatic vascular occlusion and in the group of alternate hemihepatic vascular occlusion, (620±317) (range 200-6000) ml in the group of portal triad clamping plus selective or total hepatic vein occlusion. All tumors were completely removed.Conclusions Hepatic venous occlusion applied in hepatectomy can prevent bleeding and air embolism, and is safe and effective with stable hemodynamics。

Abstract：Background Most of gynecologic malignancies are sensitive to chemotherapy. Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdrl) gene is well known for its ability to confer drug resistance. This study aimed to explore the feasibility of expression and resistance of mdrl gene transduction into human placenta mesenchymal stem cells (P-MSCs) by retrovirus vector.Methods Human P-MSCs were isolated from trypsin-digested term placentas, and their immunophenotypes and differentiation potential were evaluated. Human P-MSCs were transduced by reconstructed retroviral vector containing the mdrl gene and green fluorescent protein (GFP) reporter gene. The integration and expression of the mdrl gene were observed indirectly by the expression of GFP, and fluorescence-activated cell sorter was used to evaluate the functional activity of permeability glycoprotein (P-gp) encoded by the mdrl gene. The stimulating test was made in vitro to show pleiotropic drug resistance of transfected cells.Results The isolated, cultured and expanded P-MSCs expressed stem cell markers such as CD29, CD44 and CD73,and showed osteogenic and adipogenic differentiation potentials under appropriate conditions. The expression of P-gp in the non-transfected P-MSCs cells was (0.4±0.1)%, but increased to (28.1±4.7)% after gene transfection (P<0.01). And positive staining of P-gp located mainly at cell membrane and cytoplasm. Accumulation and extrusion assays showed that P-gp expressed by the transfected cells had pump-functional activity and could efflux daunomycin out of cells. The analysis of cell survival confirmed that transfected P-MSCs had a characteristic of multidrug resistance with a significant increase in the resistance to anticancer agents.Conclusions Transfer and expression of human mdrl gene mediated by retrovirus vector conferred P-MSCs drug resistance. It might provide a new alternative to chemoprotection strategies。

Abstract：Background Renal transplants can improve the quality of life for recipients, but the quality of their sexual life might not be improved. This study was conducted to research the prevalence of erectile dysfunction (ED) and the influential factors in male renal transplant recipients (RTRs).Methods A cross-sectional survey was conducted in three renal transplantation centers. Structured questionnaires were administrated by trained interviewers to 824 male renal transplant patients, who had active sexual lives in the last 6 months.Results Complaints of ED were reported by 75.5% of the 809 RTRs (age range 19-75 years, mean age (45±10) years),whose questionnaires were completed. Mild, moderate and severe ED were reported at 53.6%, 8.3% and 13.6%,respectively. The mean age and the graft duration were significantly higher in male RTRs with ED compared to potent graft recipients (P=-0.00 and 0.04, respectively). The prevalence of ED increased with the increase in age. It was 60.7%, 65.8%,75.2%, 87.5% and 92.2% in patients with age below 30 years, 31-40 years, 41-50 years, 51-60 years and over 60 years,respectively (P=0.000). Moreover, the severity of ED increased with aging. The percentage of moderate and severe cases of ED increased from 6.7% in patients below 40 years to 28.9% in those over 40 years (P=0.000). The prevalence of ED in the RTR who had no occupation was higher than in those who were holding a position (P=0.001). The prevalence of ED decreased with the increase in the education level. The prevalence of ED was 94.3%, 86.4%, 74.0% and 67.8% in men with elementary school or lower, middle school, high school, and college or higher degrees, respectively (P=0.000). Patients,whose distal end of arteria iliaca interna was interrupted and underwent iterative transplantation, worried transplanted kidney function was impacted by sexual life, and received cyclosporine (CsA)-based immunosuppressive regimens, were more likely to have ED (P=0.000, 0.001, 0.000, 0.000, respectively). After Logistic regression analysis, only five factors, age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life and CsA-based immunosuppressive regimens sustained their significance.Conclusions Renal transplant has varying effects on erectile function. ED is highly prevalent among RTRs and its influential factors are multiple. Age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life, CsA-based immunosuppressive regimens are the main influential factors of ED in male RTRs。

Abstract：Background Filamentous fungal infections are associated with a high morbidity and mortality in solid organ transplants.The present study aimed to investigate the aspergillus pneumonia in renal transplant recipients, and its diagnosis as well as treatment.Methods Approximately 2000 cases of renal transplants were retrospectively studied and we focused on cases hospitalized during August 1, 2005 and February 1, 2007, as the study period. The clinical database and electronic records were analyzed. Recently published literature was reviewed.Results There was more diabetes and hypertension in the infected group than in the non-infected group (86% vs 62% and 57% vs 39%, respectively). Eighty-six percent of recipients from the infected group had delayed graft function. Seven cases with aspergillus pneumonia were identified based on either fungal culture or radiology. Of the 7 cases, 4 died in a few days after diagnosis. Liposomal amphotericin B was used as a first-line therapy.Conclusions Incidences of fungal infection are increasing among renal transplant recipients. Early diagnosis and treatment are critical steps in curing aspergillosis。

Abstract：Background Total knee arthroplasties (TKR) combined with the concept of reduced trauma to tissue has been performed by many doctors. The aim of this study was to retrospectively assess the early results of a group of TKR with a mid-vastus approach, which was characterized as no patellar eversion, no disruption of suprapatellar pouch and extensor mechanism, and to compare the outcome with conventional operative techniques.Methods A total of 59 patients (67 knees) were followed. All patients received the same prosthesis of Genesis Ⅱ posterior-stabilized total knees. Of them, 29 consecutive patients (34 knees) had a mid-vastus approach and were operated on with less invasive instruments and techniques. The mean follow-up duration was 11.6 months. Clinical evaluations were performed according to the Hospital for Special Surgery scores; radiographic assessment followed the guidelines of the Knee Society. Postoperative recovery of quadriceps strength and the extensor mechanism was also evaluated.Results No prosthetic loosening or anterior knee pain was found at the latest follow-up; 1 patient had a superficial infection and postoperative stiffness of the knee who undertook a debridement and manipulation several months later. The angulations of tibial osteotomy were within normal range. The average preoperative and postoperative Hospital for Special Surgery scores were 57.9 points and 86.1 points respectively. The mean postoperative range of motion was 113.5(°-). Most patients regained their quadriceps strength at the third or fourth month postoperatively.Conclusions The overall early results from using the mid-vastus approach were comparable with that of using a standard approach, and the exposure did not affect the accuracy of the tibial cut. The muscle maximal contraction strength recovered gradually after operation. The approach was safe and patients of this group obtained satisfactory outcomes。

Abstract：Background Transradial coronary intervention has been widely used because of its effects in lowering the incidence of complications in vascular access site and improving patient satisfaction compared to the femoral approach. This study aimed to investigate the safety and feasibility of transradial approach for primary percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI).Methods A total of 103 consecutive elderly patients (age≥65 years) who were diagnosed as having AMI were indicated for PCI. Among them, 57 patients received primary PCI via the transradial approach (transradial intervention, TRI group),and 46 underwent primary PCI via the transfemoral approach (transfemoral intervention, TFI group). The success rate of puncture, puncture time, cannulation time, reperfusion time, the total time for PCI, the success rate of PCI, the use rates of temporary pacemaker and intra-aortic balloon pump (IABP), and the total length of hospital stay of the patients in the two groups were compared. After the procedure, vascular access site complications and major adverse cardiovascular events (MACE) in the two groups in one month were observed.Results The success rates of puncture (98.2% vs 100.0%) and PCI (96.5% vs 95.7%) for the patients in the TRI and TFI groups were not statistically significant (P>0.05). The puncture time ((2.4±1.1) vs (2.0±0.9) minutes), cannulation time ((2.7±0.5) vs (2.6±0.5) minutes), reperfusion time ((16.2±4.5) vs (15.4±3.6) minutes), total time of the procedure ((44.1±6.8) vs (41.2±5.7) minutes), use rates of temporary pacemaker (1.8% vs 2.2%) and IABP (0 vs 2.2%) in the two groups were not statistically significant (P>0.05), but the hospital stay of the TFI group was longer than that of the TRI group ((10.1±4.6) VS (7.2±2.6) days, P<0.01). A radial occlusion was observed in the TRI group, but no ischemic syndrome in hand. In the TFI group, 4 patients had hematosis, 1 had pseudoaneurysm, and 1 had major bleeding.Statistical significance in vascular access site complications was seen in the two groups (1.8 % vs 13.1%, P<0.05). Three patients died in the two groups respectively in one month, and there was no statistical significance in MACE in the two groups (5.3% vs 6.5%, P>0.05).Conclusion The transradial approach for primary PCI is safe and feasible for elderly patients with AMI。

Chronic kidney disease (CKD) is a significant interactive disease in patients with diabetes,hypertension, and cardiovascular disease with major morbidity consequences and high costs to the healthcare system。

Abstract：Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells".Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor.Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included.This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success。

Most cases of acute coronary syndrome (ACS) involve coronary atherosclerosis and plaque rupture,as well as subsequent thrombosis. The initial thrombotic events leading to red thrombus formation are platelet adherence and aggregation.

The term "oncocyte" was first used by Hamperl1 in 1950 to describe a kind of large, highly eosinophilic,granular tumour cell. Oncocytoma refers to the tumour that is composed of oncocytes。

Recurrent atrial tachycardia (AT) is often observed late after heart surgery and it contributes significantly to the morbidity and mortality of this group of patients. In patients with structurally normal hearts the most prevalent type of AT is a macroreentrant atrial tachycardia (MAT), more specifically known as common atrial flutter (AFL)。

Aatrochoanal polyp (ACP) is an infrequent, benign polypoid lesion that stems from the edematous mucosa of the maxillary sinus, grows from the natural or accessory ostium to the middle meatus, and protrudes toward the choana and nasopharynx.1 Although the exact causes of ACP are still unknown, chronic sinusitis, allergy,and lower respiratory tract infections are often related to ACP.2 Our report is an ACP arising from a secondary infection of the pefiapical granuloma in the maxillary sinus.

Squamous cell carcinoma of the pancreas is an unusual cancer of ductal cell origin. In a review of 6668 cases of exocrine pancreatic cancer from various registries reported from 1950 through 1985, the incidence of squamous carcinoma and adenosquamous carcinoma was 0.005% and 0.01%, respectively.1 We report a case of squamous cell carcinoma of the pancreas with liver metastasis。