Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.

Objective To investigate the effect of angiotensinⅡ(AngⅡ) type 1 receptor blocker losartan on the cyclooxygenase 2 (COX-2) expression in metabolic syndrome (MS)kidney. Methods Seven-week-old male obese Zucker rats,a model of MS,were randomly divided into losartan treated and untreated group,and lean Zucker rats were used as controls.The obese Zucker rata of treated group received losartan for 4 months continuously.COX-2 expression was examined for all rats after 4 months.AngⅡ-stimulated mesangial cells and cortical tissue from AngⅡ-infused C57BL/6 mouse kidney by osmotic minipumps were used in this study.RNA and protein were obtained from renal cortical tissue or mesangial cells for RT-PCR and Western blot.Results Compared to the lean controls,obese Zucker rats showed a significant increase of COX-2 expression in the renal cortical tissue and these abnormalities were prevented by administration of losartan. Furthermore,the direct stimulation of AngⅡincreased COX-2 expression in mesangial cells in vitro and renal cortical tissue in vivo.Conclusions MS-induced COX-2 expression in the kidney is regulated by AngⅡ.Losartan as a non COX-2 inhibitor can protect MS kidney,at least in part,by inhibition of COX-2 activation.

Objective To evaluate the safety and effectiveness of three endoscopic methods for re-moval of common bile duct stones (CBDs)accompanied with periampullary diverticula(PAD).Methods A total of 154 patients hospitalized at Taizhou Hospital and Taizhou No.1 People′s Hospital of Zhejiang prov-ince from December 2012 to July 2013 were divided randomly into three groups,i.e.,EST,EPBD and ES-BD group,and received the treatment of EST,EPBD and limited EST plus EPBD (ESBD)to extract CBDs, respectively.After 12 months of follow-up,the rate of full stone clearance,stones clearance rate in one time,the rate of mechanical lithotripsy,the rate of urgent lithotripsy,the average procedures,the average removal time and the complication incidence among three groups were compared.Results The rates of stone clearance in one time in group ESBD was higher than those of group EST and group EPBD (94.12% VS 78.43%,73.08%;P <0.05)with significant difference.The average procedures in group ESBD was lower than that of group EPBD (1.08 VS 1.31,P <0.05),which also showed significant difference.The occur-rence rates of early complication in group ESBD was lower than that of group EPBD (15.69% VS 34.61%, P <0.05).The occurrence rates of post-ERCP hyperamylasemia in group ESBD was lower than that of group EPBD (5.88% VS 21.15%)with significant difference (P <0.05).The incidence of pneumobilia in group EST was higher than those of group EPBD (52.27% VS 26.19%,P =0.013)and group ESBD (52.27%VS 27.66%,P =0.016).Conclusion The stone extraction efficiency of ESBD is better than that of EST and EPBD.Compared with conventional EST,ESBD shows similar safety level,and is safer than EPBD.So ESBD is a safe and effective method to remove CBDs with PAD.

OBJECTIVETo evaluate the hemocompatibility of glutaraldehyde (GA)-tanned bovine pericardium additionally treated by sodium bisulfite (SOB) solution.

METHODSThe hemocompatibility of GA-tanned bovine pericardium treated by SOB solution is evaluated by using dynamic clotting time test, blood platelet adhension test, D-dimeride determination, and complement activation test. The GA-tanned bovine pericardium was used as control.

RESULTSThe curve of absorbance-clotting time of two kinds of bovine pericardium was similar in dynamic clotting time test. There was no significant difference between SOB-treated and control groups in blood platelet adhension test. The D-dimeride contents of all bioprostheses were at normal level, and the D-dimeride content of GA-tanned bovine pericardium treated by SOB solution was significantly lower than that of control group (P < 0.05). In complement activation test, the level of complement C3a in SOB-treated group was significantly lower than that in control group (P < 0.05).

CONCLUSIONGA-tanned bovine pericardium treated by SOB solution meets the demands of cardiac interstitial implanted materials in hemocompatibility.

Animals ; Biocompatible Materials ; Bioprosthesis ; Blood Coagulation ; Cattle ; Complement C3a ; analysis ; Fibrin Fibrinogen Degradation Products ; metabolism ; Glutaral ; pharmacology ; Materials Testing ; Pericardium ; drug effects ; metabolism ; Platelet Adhesiveness ; Sulfites ; pharmacology

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The optimal disease staging system and treatment approaches have not yet been defined. This study aimed to evaluate the prediction of different staging systems for prognosis and treatment options of SCCE. We retrospectively accessed the clinicopathologic characteristics, treatment strategy, and prognosis of 76 patients diagnosed with primary SCCE between 2001 and 2011. The 1-, 2-, 3-, and 5-year overall survival rates were 58%, 31%, 19%, and 13%, respectively. Univariate analysis showed that the 2002 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification (P = 0.002), Veterans Administration Lung Study Group (VALSG) stage (P = 0.001), predisposing factors (P < 0.001), T category (P = 0.023), and M category (P < 0.001) were prognostic factors for overall survival. Multivariate analysis showed that the 2002 AJCC TNM stage (P < 0.001) was the only independent prognostic factor for survival. The value of the area under the receiver operator characteristic (ROC) curve (AUC) of the 2002 AJCC TNM staging system was larger than that of VALSG staging system with regard to predicting overall survival (0.774 vs. 0.620). None of the single treatment regimens showed any benefit for survival by Cox regression analysis. Thus, the 2002 AJCC TMN staging system improved the prediction of SCCE prognosis; however, the optimal treatment regimen for SCCE remains unclear.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Small Cell ; classification ; pathology ; therapy ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Esophageal Neoplasms ; classification ; pathology ; therapy ; Esophagectomy ; methods ; Etoposide ; administration & dosage ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Paclitaxel ; administration & dosage ; Radiotherapy, High-Energy ; Retrospective Studies ; Societies, Medical ; Survival Rate ; United States

OBJECTIVETo investigate the relationship between atrial fibrillation (AF) and serum soluble CD163.

METHODSA total of 336 patients with heart valve disease were included in this study, including 167 with AF and 169 with sinus rhythm. The clinical data were compared between the two grops, and Logistic regression analysis was used to identify the risk factors associated with AF.

RESULTSThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor (TNF), interleukin-6 (IL - 6), high-sensitivity C-reactive protein (hs-CRP) and left atrial diameter (LAD) all differed significantly between the two groups (P<0.05). Serum soluble CD163 levels in AF patients were significantly higher than those in patients with sinus rhythm (P<0.05). Serum soluble CD163 was positively correlated with TNF (r=0.244, P=0.244), IL-6 (r=0.186, P=0.186), hs-CRP (r=0.183, P=0.183) and LAD (r=0.194, P=0.194) in patients with AF. Logistic regression analysis showed that LAD, IL-6, TNF, hs-CRP and CD163 were all associated with AF. ROC curve analysis showed that the area under curve of serum soluble CD163 was 0.861 in patients with AF (CI 95%: 0.820-0.901, P<0.01) with a sensitivity and a specificity of 80.8 and 76.9%, respectively.

CONCLUSIONSerum soluble CD163 level may be a risk factor for AF, and an increased soluble CD163 level may indicate active inflammation in AF patients.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Atrial Fibrillation ; blood ; C-Reactive Protein ; analysis ; Heart Atria ; pathology ; Humans ; Inflammation ; blood ; Interleukin-6 ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Receptors, Cell Surface ; blood ; Risk Factors ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate reason and the management of portal vein thrombosis in patients with portal hypertension postoperatively.

METHODS329 patients with portal hypertension in liver cirrhosis who had splenectomy was reviewed from 1992 to 2001. In whom 43 (13.1%) patients with portal vein thrombosis postoperative were analyzed.

RESULTSIn these patients, except 1 died for portal vein phlebitis, all patients were recovered. There are 138 patients who underwent splenectomy or splenectomy and devascularization, 26 (18.8%) of them had thrombosis. 191 patients underwent splenectomy and portacaval or portasplenic shut, 17 (8.9%) of them had thrombosis. The data of these two groups have significant difference (chi(2) = 8.44, P < 0.01).

CONCLUSIONSThrombocytosis postsplenectomy as well as the changes of portal hemodynamics is the main reason of portal vein thrombosis. Portal vein thrombosis is also in association with the operative ways. Operation standardization, dynamic examining platelet count, routine color ultrasonography examining and early anticoagulation therapy are the effective methods in preventing and managing portal thrombosis postoperation for portal hypertension.

Adult ; Budd-Chiari Syndrome ; etiology ; prevention & control ; therapy ; Female ; Follow-Up Studies ; Humans ; Hypertension, Portal ; surgery ; Male ; Middle Aged ; Portal Vein ; pathology ; Postoperative Complications ; Vascular Surgical Procedures ; adverse effects ; methods

Objective To observe the curative effect of laparoscopic and open radical gastrectomy for gastric cancer patients and the impact on patients' CD4+CD25+T cells, oxidative stress, IL-2 and soluble receptors. Methods 120 cases from November 2009 to September 2012 were enrolled. 60 patients received laparascopic radical gastrectomy (LRG group) and 60 patients received open radical gastrectomy (ORG group) as research object, the two kinds of operation mode were compared and the impact of operation on patients' CD4+cells, oxidative stress, CD25+T IL-2 and its soluble receptor were recorded. Results The operation time, blood loss, number of lymph node dissection n LRG group were (285.8 ± 98.6), (343.3 ± 125.5), (7.8 ± 1.2), all the indexes were significantly superior to the ORG group and LRG group of patients with anastomotic leakage, intestinal obstruction, bile duct injury and pulmonary infection were 1, 1, 0, and 0 cases no difference in ORG group than MDA and AOPP, after the operation were increased, but the LRG group was lower than that of ORG group patients; postoperative antioxidant GSH-PX, SOD decreased, but LRG was higher than that of ORG group, and LRG group after treatment increased CD4+CD25+T cells in patients with the content of IL-2 of two groups after treatment, s-IL-2R increased than before LRG, group IL-2, s-IL-2R levels were (32.6 ± 4.2) and (23.6 ± 4.6) μg/ml was significantly lower than that of ORG group, P < 0.05, There was no difference in the 1, 2, 3, and 5 year survival rates between the two groups of patients. Conclusion Laparoscopic and open surgery for gastric cancer is equivalent, but also help to stabilize T cells, inhibit oxidative stress and inflammatory factors.

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.
Alzheimer Disease ; Amyloid ; Animals ; Blood Platelets ; Blotting, Western ; Brain ; Cognition Disorders ; Dementia ; Dendritic Spines ; Enzyme-Linked Immunosorbent Assay ; Excitatory Postsynaptic Potentials ; Learning ; Memory ; Metabolism ; Mice ; Mice, Transgenic ; Neurodegenerative Diseases ; Neurons ; Neuroprotective Agents ; Plant Extracts ; Plants ; Plaque, Amyloid ; Spatial Learning

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids (ω-3PUFAs) on MK-801-induced cognitive impairment in schizophrenia (SZ) rats and the underlying mechanism.A rat model of schizophrenia was induced by MK-801.The cognitive function of rats was assessed using a Morris water maze.The number of hippocampal neurons was measured by Nissl staining.The expression of CREB,p-CREB,BDNF,TrkB,p-TrkB,AKT,p-AKT,ERK,and p-ERK in the hippocampus of rats was detected by Western blotting.The results showed that ω-3PUFAs attenuated MK-801-induced cognitive,impairment and hippocampal neurons loss,reversed the injury of the CREB/BDNF/TrtB pathway induced by MK-801,and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats.In conclusion,ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT,thereby increasing the synaptic plasticity and decreashng neuron loss,and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.