Animals ; Atherosclerosis ; diet therapy ; physiopathology ; Humans ; Plaque, Atherosclerotic ; drug therapy

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.

The different biological functions were studied in mouse bone marrow-derived endothelial progenitor cells isolated by differential time attachment to obtain the optimal adherent time in this study. Density gradient centrifugation-isolated bone marrow mononuclear cells were seeded on the fibronectin-coated dish. The 1-day cultured unattached cells were seeded on the second dish for 2 more days. Then unattached cells in the second dish were seeded on the third dish. The cells on 3 dishes were defined as 1-day adherent cells, 3-day adherent cells and 3-day unattached cells, respectively. After 20-day culture, the biological functions, such as the percentage of biomarkers, the ability of adhesion, and the ability of forming tubes in vitro were analyzed. The results showed that the percentages of positive CD34, FLK-1, and CD34/FLK-1 expressions in 1-day attached cells were significantly increased compared to those in the 3-day adherent or unattached cells (P < 0.01), which showed the strongest adhesion ability. The expression of eNOS in 1- or 3-day adherent cells was significantly higher than that in 3-day unattached cells (P < 0.01). The expression of VEGF in 3-day adherent cells was significantly higher than that in 1-day adherent cells or 3-day unattached cells (P < 0.01). These results suggest the biological functions of 1-day adherent cells are significantly stronger than that of 3-day adherent or unattached cells. VEGF expression in 3-day adherent cells is higher than that in 1-day adherent cells or 3-day unattached cells. The expression of eNOS in 1-day adherent cells or 3-day adherent cells is higher than that in 3-day unattached cells. The optimal adherent time to obtain mouse bone marrow-derived endothelial progenitor cells is 1-3 d.
Animals ; Bone Marrow Cells ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cell Separation ; methods ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Leukocytes, Mononuclear ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide Synthase Type III ; metabolism ; Stem Cells ; cytology ; metabolism ; Time Factors ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study regulation of Ca(2+)-activated K(+) channels (KCa) of mesenteric artery smooth muscle cell (SMC) from 21 old patients with essential hypertension (EH) by endothelin-1 (ET-1) and prostagl E(1) (PGE(1)).

METHODSMesenteric artery branch from EH was digested by enzyme. Patch clamp technique was used to pull cell-attached and inside-out patches on mesenteric artery SMC from EH and the normotensive patients respectively. The signal channel open probability (Po), open dwell-time (To) and close dwell-time (Tc), open channel number per patch were recorded. After adding Ca(2+) (10(-8) approximately 10(-6) mol/L), ET-1(2 approximately 8 x 10(9) mol/L) and PGE(1) (10, 20, 40, 100, 200, 400 nmol/L) to cytoplasm respectively. The parameters above were observed again.

RESULTSCompared to that of normotensive patients, the activities of KCa channels of patients with EH was higher. After adding Ca(2+) to cytoplasm,the Po of KCa channels in normotensive patients increased significantly. But it was few changes in EH group. KCa channels has dual reaction to ET-1 in normotensive patients. We have found no statistics difference when ET-1 present on KCa channels of EH cases. Whereas PGE(1) can affect KCa channels current and channels kinetic significantly in side-out patches. The Po of KCa channels increased. The To protracted and the Tc curtailed in EH.

CONCLUSIONSThe activities of KCa channels of patients with EH increased significantly. but the sensitive to Ca(2+) decreased. ET-1 were few effect to KCa channels. The PGE(1) can activated KCa channels of patients with EH.

Aged ; Alprostadil ; pharmacology ; Cells, Cultured ; Endothelin-1 ; pharmacology ; Female ; Humans ; Hypertension ; metabolism ; physiopathology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; cytology ; Middle Aged ; Muscle, Smooth ; metabolism ; physiopathology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; drug effects ; metabolism

Objective　To study the effect of acute serious smoke inhalation injury to unilateral lung on contralateral lung and the therapeutic efficacy of massive bronchoscopic lavage with saline to the primary injured bronchoalveolus at early stage after smoke inhalation on mitigating the secondary damage of the other lung and so as to confirm the therapeutic validity of lung lavage to smoke inhalation injury. Methods　Fifteen mongrel dogs were insufflated with sawdust smoke into left lung and then randomized into 2 groups. The dogs in group A were maintained intravenous glucose saline transfusion and breathed air freely for 24 h after injury. Those in group B received a massive bronchoscopic lavage with 250 ml of saline to injured lung at 1 hour after injury and then were administrated similarly to those in group A. Gas exchange function of bilateral lungs in the process were observed and pathologic and phyiopathologic changes of the lung specimen were examined after the process. Results　While the total lavaging volume was kept to 250 ml, the liquid volume remained in left lung after each operating was from 90 ml to 140 ml. All animals had a significant decline in pulmonary function after smoke inhalation injury. PaO2 in group B decreased significantly soon after the lavage and then increased gradually to exceeding that in group A. The left lung showed serious edema similarly in two groups but in right lung the water content was less, dynamic and static compliance was more in group B than in group A. Conclusion　Bronchoalveolar massive lavage at early post-injury stage to injured lung after unilateral lung smoke inhalation injury can mitigate secondary damage of the non-injured lung. Lung lavage can decrease the intensity of secondary systemic inflammatory reaction and show a therapeutic validity to smoke inhalation injury.

Objective　To investigate the existence, intensit y and persisting time of biologic activity of bronchoalveolar lavage fluid (BALF ) collected from dogs with acute severe smoke inhalation injury in early post-i njury stage. Methods　BALF was collected 1 h after the est ablishment of acute severe sawdust smoke inhalation injury in 5 dogs, and the fl uid was perfused into the lungs of Wistar rats in the amount of 5 ml/kg (gro up C). Normal saline (group A) and BALF from normal dog (group B) were perfused into the lungs of rats and served as control. The respiratory rate, PaO2, lung water content and the expanding stability of lungs in all rats were determ ined at the time points of 4,12 and 24 h after the purfusion. Results　 Compared with the rats in group A and B, the rats in group C had higher mortality, wider range in RR, higher lung water content, PaO2 decreased obviou sly and lower lung expanding stability. The rats in control groups showed sl i ght mechanic obstruction in their airways in the course of experiment. Meanwhile ，the rats in group C showed higher oxidative activities and lower total anti-o xidative activities in lung tissues. Conclusion　It is certai n that the BALF collected from dogs with acute severe smoke inhalation injury in early post-injury stage could induce obvious injury in lung structure of norma l rats, showing certain mechanic obstruction in small airways. The injuring act ivity of the BALF can be alleviated ultimately 24 h after the perfusion of the B ALF.

OBJECTIVETo investigate the biological activities of the bronchoalveolar lavage fluid (BALF) harvested from dogs with smoke inhalation injury at early post injury stage.

METHODSBALF was harvested from normal dogs and those inflicted by smoke inhalation injury for the employment in the study. Ninety four Wistar rats were employed in the study and were randomly divided into A (n=28), B (n=29) and C (n=37) groups. The rats were perfused intra-tracheally with normal saline, BALF from normal dog and BALF from injured dog, respectively in A, B and C groups. Every 7 rats in each group were used before the perfusion as normal control. The rats in control group and those in A, B and C groups at 4, 12 and 24 hours after BALF perfusion were sacrificed. The survival rate and the pathomorphological gross and microscopic changes in pulmonary tissue in all groups were observed. In addition, the contents of prostaglandin F1alpha/thromboxane B2 (PGF1alpha/TXB2), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) in pulmonary tissue homogenization and the pulmonary capillary permeability were determined simultaneously.

RESULTSAll the rats in A and B groups survived, but nine in C group died before sacrificing. The BALF from dogs inflicted by smoke inhalation injury could cause rat lung exhibiting pathomorphological changes similar to those in rats inhaling smoke directly. The rat pulmonary tissue contents of PGF1alpha/TXB2 in A and B groups after the perfusion tended to increase, while that in C group decreased gradually (P <0.01). The rat pulmonary tissue contents of TNF-alpha and MPO content in A and B groups after the perfusion revealed no obvious change (P >0.05), while those in C group increased evidently at 4 hour after the perfusion and decreased thereafter (P <0.05-0.01). The pulmonary capillary permeability in C group was higher than that in A and B groups at 4 hour after the perfusion (P < 0.01).

CONCLUSIONThe BALF from canine lungs during the early stage of inhalation injury exhibited biological activities. The primary and secondary pulmonary injury could be prevented or ameliorated by massive pulmonary lavage during early post injury stage after smoke inhalation injury.

Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; Dogs ; Lung ; pathology ; Male ; Rats ; Rats, Wistar ; Smoke Inhalation Injury ; pathology

OBJECTIVETo establish a canine model of severe smoke inhalation injury on unilateral lung, in order to observe the pathomorphological changes in the injured lung within 24 postburn hours (PBHs).

METHODSTwenty five mongrel dogs were employed in the study and randomized into 3 groups. The left lung was injured by inhaling smoke produced by burning sawdust with sparing the right lung with a breathing tube in 10 dogs in group A. A conventional model of smoke inhalation injury to bilateral lungs was reproduced in 8 dogs in group B, and dogs in group C not subjected to smoke inhalation served as controls. Hemodynamic changes, blood gas analysis and the pathophysiologic changes in the lungs were observed within 24 PBHs.

RESULTSAll of the dogs in groups A and C survived. Hemodynamic indices in the dogs in groups A and C remained stable without showing signs of systemic hypoxia. The arterial oxygen partial pressure in dogs of group A was 65 +/- 5 mm Hg, and the oxygen saturation in the mixed blood was 0.64 +/- 0.04 at 24 PBHs, and they were much lower than those in group C but higher than those in group B. The pathological changes in the injured side of the lungs in group A were similar to those in group B with high consistency, and the changes, though milder, could also be identified in the contralateral uninjured lung. Five dogs died in the group B within 24 hours after smoke inhalation and the survivors showed signs of multiple organ failure.

CONCLUSIONThe canine model of acute severe unilateral pulmonary smoke inhalation injury was reproduced reliably, and could be an ideal model for the study on smoke inhalation injury.

Animals ; Burns, Inhalation ; Disease Models, Animal ; Dogs ; Lung Injury ; chemically induced ; Male ; Random Allocation ; Smoke Inhalation Injury

OBJECTIVETo investigate the factors that influence survival of the patients with differentiated thyroid carcinoma in young people and evaluate the efficiency of unilateral lobectomy plus isthmectomy with therapeutic cervical lymph node dissection and postoperative TSH (thyroid stimulating hormone) suppressive therapy.

METHODSOne hundred and thirty-one patients under 30 years old with differentiated thyroid carcinoma treated in this hospital (14 cases no more than and 117 cases more than 16 years) from Jan. 1st, 1985 to Dec. 31st, 1997 were retrospectively reviewed. One hundred and twenty-eight patients were received only surgery and TSH suppressive therapy, and 3 patients received chemotherapy or radiotherapy because of the progressive metastasis in necks or mediastina. A multivariate analysis was performed in these patients by the Cox proportional hazard model.

RESULTSThe mean follow-time (x +/- s) of all patients were (140.86 +/- 43.76) months, with range from 20 to 229 months; Ninety-eight patients followed more than 10 years. Ten patients died of thyroid cancer. The overall 10-year survival rate was 97.18%. The 10-year survival rate for patients < or = 16 years of age and > 16 years were 75.97% and 96.57% respectively (P = 0. 0006). The 10-year survival rate for women and men were 94.91% and 93.69% respectively (P = 0.5261). The 10-year survival rates of patients with papillary thyroid carcinoma and follicular thyroid carcinoma were 93.77% and 96. 55% respectively (P = 0.8137). For patients with tumor size of < or = 1 cm, 1-4 cm and >4 cm the survival rate was 100.0%, 96.40%, and 80.67% respectively (P = 0. 0589). The 10-year survival rates of patients with or without lymph node metastasis were 88.37% and 100. 0% respectively (P = 0.0313). For patients of with or without distant metastasis, The survival rate was 96.64% or 60.00% (P = 0.0000). The 10-year survival rates with or without recurrence were 86. 67% and 95.48% respectively (P = 0. 5681). Using multivariate analysis, risk factors that independently influence survival were distant metastasis, tumor size and age.

CONCLUSIONSThe distant metastasis, tumor size and age at diagnosis were the independent factors influencing survival significantly. The status of lymph node metastasis may have certain effect on the prognosis. Unilateral lobectomy plus isthmectomy with a therapeutic cervical lymph node dissection followed by postoperative TSH suppressive therapy is a favourable model to children and young adults with DTC without distant metastasis, but to the patients with distant metastasis, their prognosis of this therapy model is disappointing.

Adenocarcinoma, Follicular ; mortality ; pathology ; surgery ; Adolescent ; Adult ; Child ; Female ; Humans ; Lymphatic Metastasis ; Male ; Papilloma ; mortality ; pathology ; surgery ; Prognosis ; Retrospective Studies ; Survival Rate ; Thyroid Neoplasms ; mortality ; pathology ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the therapeutic efficacy of double-mutated oncolytic adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer in an orthotopic nude mouse model.

METHODSThe susceptibility to the adenovirus was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with 5-bromo-4-chloro-3-indolyl-β-galactoside (X-Gal). Immunostaining against adenoviral hexon protein was performed to determine the selective replication of AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1 cells in S phase of cell cycle after adenovirus infection. Cell viability after AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder cancer model was established in nude mice, and the inhibitory efficacy of intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed.

RESULTSGene transduction efficiency was different among the cell lines, and correlated with expression of CAR. 5637 and KK47 cells with high expression of CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with little CAR expression were resistant to adenoviral infection. Immunostaining showed that the expression levels of hexon protein varied among the cell lines. Normal cells infected with AxdAdB-3 expressed little hexon protein. The proportion of S-phase cells was (39 ± 3) % and (49 ± 5) % in the AxCAlacZ- and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with gemcitabine significantly inhibited the growth of bladder cancer cell lines. In vivo, the mean weight of the bladder tumors in mice treated with intravesical instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were 400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the combination therapy reduced tumors more effectively than either AxdAdB-3 (P < 0.0001) or gemcitabine (P < 0.0001) alone.

CONCLUSIONSIntravesical instillation therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the orthotopic bladder cancer in nude mouse, and further relevant clinical studies are guaranteed.

Adenoviridae ; genetics ; Administration, Intravesical ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; therapeutic use ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Galactosides ; Indoles ; Mice ; Mice, Nude ; Models, Animal ; Urinary Bladder Neoplasms ; drug therapy