Objective To investigate the effects of Mycobacterium vaccae vaccine on immunological function and clinical character in elderly patients with stable chronic obstructive pulmonary disease (COPD). MethodsA total of 100 elderly patients with stable COPD were randomly divided into immunotherapy group (group A, n= 50) and non-immunotherapy group (group B, n= 50), and normal control group (group C, n = 50). The levels of peripheral blood T-lymphocyte subsets (CD3+ , CD4+, CD8+ , CD4+/CD8+ ratio), natural killer cells (NK cells), immunoglobulins (IgG, IgA, IgM) and cytokines (IL-6, IL-8, TNF-a) were measured respectively before and after therapy. Group A and B were followed up for 1 year, then the times of acute outbreak and hospitalization of patients in the two groups were also compared. Results The levels of CD4 + ,CD4+/CD8+ ratio and NK cells in group A, B were significantly lower before therapy (P＜0. 05～0. 01＝, and the levels of IL-6, IL -8, TNF-a and IgA were significantly higher than in group C (P＜0. 01＝. After treatment with Mycobacterium vaccae vaccine in group A, the levels of CD4+ , CD4+/CD8+ ratio and NK cells were significantly higher (P＜0. 05-0. 01＝ and IL-6, IL-8, TNF-a and IgA were significantly lower than before treatment (all P＜0. 01＝. These levels showed no significant changes in group B after treatment (P＞0. 05). After 1-year follow-up, the times of acute outbreak and hospitalization on patients were statistically lower in group A than in group B (P＜ 0. 01 ).ConclusionsMycobacterium vaccae vaccine can improve cellular immunity function and reduce the times of acute outbreak and hospitalization in patients with stable COPD, so it has a higher clinical application value.

Objective Diabetic mice models were established.Hearts were separated from the body,reperfused after ischemia,and disposed of with the extraneous calcitonin gene-ralated peptide (CGRP),to prove if the CGRP had protective effect on the early-staged diabetic mice with cardiac ischemia.Method ICR mice were injected with Streptozocins intraperitoneally to establish diabetic model.The model mice and the normal mice were randomly divided into 4 groups:two diabetic groups,two control groups.Hearts of the experimental mice were taken out from the chest cavity alive,and hanged on the Langendorff steadily for 30min.Western blot and radioimmunoassay techniques were used to test expression of Vanilloid receptor(VR1) and CGRP in myocardic tissue;Madlab system was used to test the cardiac function,which including left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),heart rate (HR),and coronary artery flow (CF),in the process of ischemic reperfusion,And ELISA assay kit was used to measure the concentration of the lactate dehydrogenase (LDH) in perfusion fluid collected from the heart.Result Expressions of VR1 and CGRP in diabetic hearts were significantly lower than those in normal ones 2 weeks later(P＜0.01).By comparing with normal hearts,diabetic hearts had higher LVEDP and CF (P＜0.05),and lower LVDP and HR(P＜0.05).However,release of LDH were lower than normal ones (P＜0.05).Predisposition of normal and diabetic hearts with CGRP can improve the cardiac function after ischemie injury.And the beneficial effect was more profound in early-staged diabetic hearts than in normal ones.Conclusion The diabetes disease(DM) can impair the expression of CGRP in myocardiac tissue.The extraneous CGRP may exert more potent protective effect on cardiac function in the early-staged diabetic heart.

OBJECTIVETo build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.

METHODSThirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.

RESULTSValidation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.

CONCLUSIONThis method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.

Drug Design ; Enzyme Inhibitors ; Epidermal Growth Factor ; metabolism ; Models, Chemical ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the effect of antidepressant on irritable bowel syndrome (IBS).

METHODSA self-control and follow-up study on subclinical dosage of antidepressants therapy (fluoxetine 10 mg/d, paroxetine 10 mg/d or doxepin 45 mg/d) for 9-12 wks in 46 patients with refractory IBS symptoms according to Rome II criteria was performed, the clinical outcomes were evaluated by scales changes of symptom-related-anxiety, severity index of symptom, and quality of life specific of IBS, as well as general psychiatric health by SCL-90 during treatment and follow-up periods.

RESULTSAll 46 cases completed therapy and first follow-up unit (12 wks after treatment) (FFU), at the end of FFU, clinical symptoms in all patients were improved (P < 0.01). Comparison of the scores of symptom-related-anxiety, index of symptom, and quality of life specific of IBS at the end of FFU with that at basal level, indexes of the severity (3.4 +/- 1.5 vs 1.8 +/- 0.84) and frequency (3.8 +/- 1.60 vs 2.0 +/- 0.76) of symptoms were subsided significantly (P < 0.01, respectively); the scores of symptom-anxiety questionnaire including body anxiety (16.04 +/- 1.65 vs 10.83 +/- 1.64, P < 0.001), cognitive anxiety (18.78 +/- 2.12 vs 11.17 +/- 1.89, P < 0.001), fear (15.80 +/- 1.76 vs 10.78 +/- 1.85, P < 0.001) and avoiding (15.47 +/- 1.53 vs 10.16 +/- 1.59, P < 0.001) were also subsided significantly. In the meantime, IBS-QoL improved significantly (P < 0.05), dysphoria, body image, interference with activity, health worry, social reaction and overall scores were improved significantly (P < 0.01, respectively). The status of general psychiatric health was also improved significantly (P < 0.01).

CONCLUSIONSTreatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.

Adult ; Antidepressive Agents ; administration & dosage ; Doxepin ; administration & dosage ; Female ; Fluoxetine ; administration & dosage ; Follow-Up Studies ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Paroxetine ; administration & dosage ; Quality of Life

Objective To investigate prognostic factors of medullary thyroid carcinoma.Methods By using univariate analysis and multivariate analysis,the prognostic factors were investigated in 102 patients with medullary thyroid carcinoma treated at this hospital.Results Overall survival rates of 5-year,10-year and 15-year were 87.4%,74.6%and 54.2%respectively by Kaplan-Meier method analysis.In univariate analysis,gender,age,bilateral thyroid lobe tumors,tumor size＞4 cm,invasion of thyroid capsule,distant metastasis,and non-radical tumor resection were significant poor prognostic factors.In multivariate analysis,tumor size＞4 cm(X2=7.43,P=0.0035),distant metastasis(X2=23.50,P=0.0000),and non-radical tumor resection(X2=25.90,P=0.0000)remained as independent pmgnostic factors.Conclusions Tumor size＞4 cm,distant metastasis,and non-radical tumor resection are the independent predictors of patients survival.Early diagnosis and early therapy can improve significantly the prognosis of medullary thyroid carcinoma.

OBJECTIVETo investigate the effects of small interfering RNA targeting connective tissue growth factor (CTGF) on rat transforming growth factor beta (TGF beta)/Smads signal pathway.

METHODSChemically synthetic siRNA targeting CTGF was transfected into HSC T6 and then they were injected into rat livers through their intraportal veins. At the same time these rats also received CCl4 subcutaneously every three days for 6 consecutive weeks. Untreated HSC T6 or/and rats with random siRNA treatment served as controls. Total RNA or/and protein in HSC T6 and rat hepatic tissues were extracted. The expressions of CTGF and TGF beta 1, Smad2, 3 and 7 genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot.

RESULTSCTGF siRNA significantly reduced the expression of CTGF protein in HSC T6. At 48 h after CTGF siRNA treatment, the down-regulation of CTGF protein was the most significant, up to 94%+/-4% (t=46.196, P less than 0.01), but the expressions of TGF beta 1, Smad2, 3 and 7 mRNA showed no differences in HSC T6 compared with the blank controls. Six weeks after CCl4 injections, prominent up-regulations were observed in the gene expressions of CTGF and TGF beta 1 in saline control or siRNA-treated rat livers. Administering CTGF siRNA for six weeks markedly attenuated the induction of CTGF and TGF beta 1 genes; the expressions of CTGF and TGF beta 1 protein decreased by 95%+/-2% (F=21.234, P less than 0.01) and 74%+/-8% (F=13.464, P less than 0.05), respectively, whereas Smad2, 7 protein expressions were not affected.

CONCLUSIONSilencing the CTGF gene can suppress the TGF beta /Smads signal pathway in rat livers.

Animals ; Connective Tissue Growth Factor ; metabolism ; Gene Silencing ; Male ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad Proteins ; metabolism ; Transfection ; Transforming Growth Factor beta ; metabolism

Objective: To observe the effects of angina pector is on severe ventricular arrhythmia and QTd in patients with first acute myocard ial infarction(AMI). Methods: One hundred and eight-four cases of first AMI were divided into 2 groups: PA group, angina pectoris occurred with in 24 h before AMI onset (n=58), NPA group, no preceeding angina pectori s occurred (n=126). Occurrence of complications and QTd were investigated du ring hospitalization. Results: The basic clinical characteristic s, coronary risk factors, medication before infarction, treatments after admissi on with antiarrhythmic agents, site of infarction, successful rate of thrombolys is and peak CK, CK-MB were not statistically different. Early QTd in PA group and NPA group were (56.22±18.40) ms vs (84.45±21.90) ms, respectively, P <0.05, late QTd in PA group and NPA group were (50.67± 16.34) ms vs (64.1 8(16.41) ms, respectively, P<0.05. Comparison with NPA group, incidence of severe ventricular arrhythmia, heart failure, cardiogenic shock and rate of car diac mortality in-hospital was lower in PA group. Conclusion: P reinfarction angina pectoris can significantly reduce the incidence of severe ve ntricular arrhythmia and QTd in the patients with first AMI, sugges ting that these favorable effects might be associated with protective effects of ischemic preconditioning on myocardium and ventricular pump function and improv ement of repolarizative asynchronism in ventricular myocardium.

Objectives To construct the cancellous bone explant model and a method of culturing these bone tissues in vitro, and to investigate the effect of mechanical load on growth of cancellous bone tissue in vitro.
Methods Cancellous bone were extracted from rabbit femoral head and cut into 1-mm-thick and 8-mm-diameter slices under sterile conditions. HE staining and scanning electron microscopy were employed to identify the histomorphology of the model after being cultured with a new dynamic load and circulating perfusion bioreactor system for 0, 3, 5, and 7 days, respectively. We built a three-dimensional model using microCT and analyzed the loading effects using finite element analysis. The model was subjected to mechanical load of 1000, 2000, 3000, and 4000μεrespectively for 30 minutes per day. After 5 days of continuous stimuli, the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) were detected. Apoptosis was analyzed by DNA ladder detection and caspase-3/8/9 activity detection.
Results After being cultured for 3, 5, and 7 days, the bone explant model grew well. HE staining showed the apparent nucleus in cells at the each indicated time, and electron microscope revealed the living cells in the bone tissue. The activities of AKP and TRAP in the bone explant model under mechanical load of 3000 and 4000μεwere significantly lower than those in the unstressed bone tissues (all P<0.05). DNA ladders were seen in the bone tissue under 3000 and 4000μεmechanical load. Moreover, there was significant enhancement in the activities of caspase-3/8/9 in the mechanical stress group of 3000 and 4000με(all P<0.05).
Conclusions The cancellous bone explant model extracted from the rabbit femoral head could be alive at least for 7 days in the dynamic load and circulating perfusion bioreactor system, however, pathological mechanical load could affect the bone tissue growth by apoptosis in vitro. The differentiation of osteoblasts and osteoclasts might be inhibited after the model is stimulated by mechanical load of 3000 and 4000με.

AIMDesign, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.

METHODS AND RESULTSCoupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.

CONCLUSIONFive target compounds were found to be potential farnesyltransferase inhibitors.

Alkyl and Aryl Transferases ; antagonists & inhibitors ; drug effects ; Benzodiazepines ; chemical synthesis ; chemistry ; pharmacology ; Farnesyltranstransferase ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Molecular Conformation ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo analyze the clinical features of adrenal metastasis.

METHODSFrom January 1993 to December 2004, 103 cases of adrenal metastasis were reviewed.

RESULTSLung and hepatocellular carcinoma were the most common primary tumor of adrenal metastatic tumor, which about 36.9% (38/103) and 42.7% (44/103) of all cases, followed by renal carcinoma 6.8% (7/103), colorectal carcinoma 4.9% (5/103), stomach carcinoma 3.9% (4/103), breast cancer 1.9% (2/103), unknown primary tumor 2.9% (3/103). Most of these were low differentiation. The mean diameter of adrenal metastasis was 3.9 cm. The mean interval from detection of primary tumor to adrenal metastasis was 9.5 months. And 79.6% (82/103) were detected as a part of multiorgan metastasis. Only 5 cases (4.9%) were presented with pain in the back. There was little characterization of ultrasonography, CT and MRI, color-Doppler and selective arterial imaging showed little blood supply. All of patients were treated with synthetic methods, 16 cases (15.5%) who had undergone adrenalectomy for metastasis disease had a improved survival compared with those non-adrenalectomy.

CONCLUSIONSThere is no particular presentation of clinic and imaging, diagnosis depending on history, follow-up and the pathological presentation of primary tumor. There are no standard treatment guidelines for this group of patients. When the primary tumor could be resected or be well controlled, and there is no other evidence of metastasis, adrenalectomy is recommended. Transarterial chemoembolization (TACE) could not actually be performed.

Adrenal Gland Neoplasms ; diagnosis ; secondary ; therapy ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; pathology ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms ; pathology ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Survival Analysis ; Treatment Outcome