Humans ; Male ; Middle Aged ; Thyroid Cartilage ; abnormalities

BACKGROUNDCurrently, 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.

METHODSHind 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.

RESULTSIn 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 untreated 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.

CONCLUSIONSDiabetes 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.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; physiopathology ; Extremities ; blood supply ; Fibroblast Growth Factor 2 ; genetics ; Neovascularization, Physiologic ; drug effects ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type III ; metabolism ; Perindopril ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Streptozocin ; Vascular Endothelial Growth Factor A ; genetics

Objective To investigate the epidemiologic characteristics of patients with severe acute pancreatitis (SAP) and the effects of its complications on prognoses in past 7 years in the north area of Guizhou province. Methods Data of 209 patients with SAP admitted to the Department of Critical Care Medicine of Affiliated Hospital of Zunyi Medical College from January 2009 to January2016 were retrospectively analyzed, and they were divided into a survival group (178 cases) and a death group (31 cases) according to the prognosis. The gender, age, diagnosis (primary and recurrent), the length of stay in hospital, the levels of creatinine and total bilirubin (TBil), the time of blood purification, hematocrit (HCT) level on the first day after admission, pathogenesis, complications [infection, pseudocyst, intra-peritoneal hemorrhage, acute renal failure (ARF), acute respiratory distress syndrome (ARDS), abdominal compartment syndrome (ACS), pancreatic encephalopathy, multiple organ dysfunction syndrome (MODS)], sequential organ failure (SOFA) score (maximum SOFA score during hospital stay), application of hormones, surgical interference, etc. related factors were compared, the SAP epidemiological characteristics, factors affecting prognosis and the effect of complications on prognosis in intensive care unit (ICU) were analyzed in the two groups.Results Of the 209 patients 98 cases were diagnosed biliary pancreatitis accounting for the majority (46.9%), hyperlipidemic pancreatitis 76 cases (36.3%), alcoholic pancreatitis 6 cases (2.8%) and idiopathic pancreatitis29 cases (13.9%). The age (years: 47.1±13.5 vs. 53.2±12.0), creatinine (μmol/L: 109.4±100.3 vs. 335.7±222.4), the ration of intra-peritoneal hemorrhage [4.5% (8) vs. 38.7% (12)], ARF [1.1% (2) vs. 54.8% (17)], ACS [1.1% (2) vs. 9.7% (3)], MODS [18.5% (33) vs. 74.2% (23)] and SOFA score (3.3±2.4 vs. 10.5±5.4), percentage of patients using hormones [5.6% (10) vs. 29.0% (9)] were significantly lowered (allP < 0.05) and the time of blood purification was shortened (days: 1.95±1.97 vs. 4.81±5.84) in survival group than those in death group; while the gender, diagnosis, the length of stay in hospital, TBil, HCT on the first day after admission, pathogenesis, complications (infection, pseudocyst, ARDS and pancreatic encephalopathy) and surgical treatment situation were compared between the two groups, no statistical significant differences were seen (allP > 0.05). Logistic regression analysis showed that creatinine > 300μmol/L [odds ratio (OR) was 2.651, 95% confidence interval (95%CI) was 1.459-3.935,P = 0.017], intra-peritoneal hemorrhage (OR was 5.231, 95%CI was 3.517-7.159,P = 0.000), ARF (OR was 3.731, 95%CI was 2.641-4.857,P = 0.000), ACS (OR was 2.517, 95%CI was 1.003-3.098,P = 0.000), use of hormone (OR was 1.012, 95%CI was 0.825-2.051,P = 0.000) and SOFA score (OR was 3.179, 95%CI was 2.630-6.021 andP = 0.000), MODS (OR was 4.716, 95%CI was 2.086-7.902 andP = 0.031) were the risk factors having critical effects on the prognosis of thedisease, The higher the creatinine level, the worse the prognosis. The mortality of ARF was very high reaching 89.5%; the mortalities of patients with complications as intra-peritoneal haemorrhage, ACS, MODS, pancreatic encephalopathy, AKI, infection, pancreatic pseudocyst and ARDS were as follows: 60.0%, 60.0%, 41.1%, 33.3%, 32.1%, 23.1%, 17.7%, 13.1% respectively.Conclusion Biliary disease andhyperlipidemia are the major causes of SAP in north area of Guizhou province, creatinine > 300μmol/L, intra-peritoneal hemorrhage, ARF, ACS, SOFA score, use of hormones are the independent risk factors leading to poor outcome in patients with SAP and the use of hormones cannot ameliorate the disease situation.

Animals ; Genetic Vectors ; HEK293 Cells ; Humans ; Lentivirus ; genetics ; Rats

OBJECTIVESTo investigate the relationships among rotational alignment reference axes of distal femur and tibial mechanical axis, and determine the safest rotational alignment reference axis.

METHODSDigital photos were taken of 30 cadaveric lower extremities with knee in extension and flexion at 90 degrees , angles were measured among tibial mechanical axis and a line perpendicular to clinical epicondylar axis, a line perpendicular to surgical epicondylar axis, Whiteside's line and femoral mechanical axis. Statistical analysis of relationships among those axes were performed.

RESULTSThe angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, a line perpendicular to the surgical epicondylar axis, Whiteside's line and femoral mechanical axis were 0.6 degrees varus, 3.9 degrees varus, 0.2 degrees valgus and 3.0 degrees varus respectively. The angle between the femoral mechanical axis and the tibial mechanical axis was significantly larger than the angles among the tibial mechanical axis and a line perpendicular to the clinical epicondylar axis, the Whiteside's line (P < 0.05). There was no significant difference compared with the angle between a line perpendicular to the surgical epicondylar axis and the tibial mechanical axis. Angles of the clinical epicondylar axis, the surgical epicondylar axis and the Whiteside's line between knee extension and flexion were 2.3 degrees valgus, 0.9 degrees varus and 3.1 degrees valgus respectively.

CONCLUSIONThe surgical epicondylar axis rather than the clinical epicondylar axis or the Whiteside's line is the safest femoral rotational alignment reference axis intraoperatively.

Arthroplasty, Replacement, Knee ; Biomechanical Phenomena ; Femur ; anatomy & histology ; surgery ; Humans ; Knee Prosthesis ; Rotation ; Tibia ; anatomy & histology ; surgery

OBJECTIVETo evaluate the role of adiponectin in regulating tumor necrosis factor alpha (TNF alpha) production and preventing fulminant autoimmunological damage of hepatocytes following concanavalin A (Con A) injection into mice.

METHODSThree days after recombinant plasmids pAA-neo-mAd were injected into the mice via the tail veins, Con A was injected into the mice. Mice transfected with empty pAA-neo vector served as controls. The serum levels of alanine aminotransferase (ALT), TNF alpha and adiponectin were detected, and histological examination of livers was carried out at different time points after the Con A injection. All results were subjected to statistical analyses.

RESULTSHistological examinations showed that the damage in livers of mice with high serum adiponectin levels was milder than that of the controls. The serum levels of ALT and TNF alpha were both lower than those of the controls (P less than 0.01, respectively). Statistical analyses showed the serum levels of ALT was negatively related to the levels of adiponectin in the sera (r=-0.5034).

CONCLUSIONAdiponectin is effective in protecting hepatocytes from Con A-induced immunological injury. The mechanism of this protective effect may be caused by inhibiting the synthesis and/or release of TNF alpha.

Adiponectin ; blood ; pharmacology ; Alanine Transaminase ; blood ; Animals ; Concanavalin A ; adverse effects ; Female ; Immune System Diseases ; chemically induced ; pathology ; prevention & control ; Liver ; drug effects ; pathology ; Liver Diseases ; pathology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

Apoptosis ; Cell Line ; Cell Line, Tumor ; Genes, Viral ; Hepatitis B virus ; genetics ; Hepatocytes ; cytology ; Humans ; Trans-Activators ; genetics

OBJECTIVETo sum up causes and the prevention of complications after using the radio frequency ablation (RFA) to treat of primary and secondary liver cancers.

METHODSThe clinical courses of 735 patients, undergoing percutaneous RFA treatment for a total of 1780 times were reviewed. The causes of the complications occurring after the RFA treatment, and their prevention and treatment were evaluated.

RESULTSEleven complications after RFA treatment were found. Postoperative fever, sweating, and local pain were common. Serious complications, such as gut perforation, intraabdominal hemorrhage, and cardiovascular accident were found in 4 patients, and the mortality was 75%.

CONCLUSIONSThe RFA treatment is an effective method for the treatment of primary and secondary liver tumor. Careful selection of patients, appropriate preoperative preparations, proper operative procedures, and suitable postoperative care are the key points in preventing the complications.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; secondary ; surgery ; Catheter Ablation ; adverse effects ; Female ; Humans ; Liver Neoplasms ; secondary ; surgery ; Male ; Middle Aged

Adenocarcinoma ; diagnosis ; metabolism ; pathology ; secondary ; Brain ; metabolism ; pathology ; Brain Neoplasms ; diagnosis ; metabolism ; pathology ; secondary ; Carcinoembryonic Antigen ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Keratin-7 ; metabolism ; Lung Neoplasms ; pathology ; Magnetic Resonance Imaging ; Middle Aged ; Nuclear Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVETo explore the feasibility of transfecting DHFR (human double-mutant dihydrofolate reductase) gene into mouse bone marrow cells and the effect of resistance to high dose MTX chemotherapy.

METHODSAfter DHFR gene was transfected into mouse bone marrow cells with retroviral vector, the cells were treated with methotrexate (MTX) and then CFU-GM (granulocyte-macrophage colony-forming unit) assay was performed. Peripheral blood leucocytes and platelets, body weight and survival rate were observed. After treatment with high dose MTX, the expression of drug resistance gene was checked by RT-PCR in the transfected bone marrow cells.

RESULTSSFG-F/S-NeoR gene-transfected mice bone marrow cells yielded drug-resistance colonies to MTX (donor mice: 15.8%, recipient mice: 18.0%, control: 0) The peripheral blood leucocytes and platelets, body weight recovered gradually and the survival rate was 83.3% at the 40th day, while 0 in controls in gene transfected mice after large dose MTX treatment. RT-PCR of transgenic mouse marrow cells showed the band of F/S gene (400 bp).

CONCLUSIONDHFR gene can not only be integrated and expressed in bone marrow cells but also improve their drug-resistence to MTX.

Animals ; Antimetabolites, Antineoplastic ; pharmacology ; Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Bone Marrow Transplantation ; Cells, Cultured ; Drug Resistance, Neoplasm ; genetics ; Erythrocyte Count ; Genetic Vectors ; Leukocyte Count ; Male ; Methotrexate ; pharmacology ; Mice ; Mice, Inbred BALB C ; Mutation ; Retroviridae ; genetics ; Survival Analysis ; Tetrahydrofolate Dehydrogenase ; genetics ; metabolism ; Transfection