To investigate the effects of Losartan,an angiotensinⅡ(AngⅡ)receptor(AT_1) antagonist,on pancreatic stellate cells(PSCs)and its possible mechanisms.Methods (1)PSCs were isolated from pancreatic cancerous samples to test the expressions of AT_1 and collagenⅠafter incubated with AngⅡor/and Losartan.(2)Ninety S-D rats were divided into normal group,control group and treatment group,with 30 rats in each.The rats in control and treatment groups were induced pancreatic fibrosis by injection of 2% trinitrobenenze sulfonic acid(TNBS)into biliopancreatic duct.Rats in treat- ment group were then treated with Losartan by garage daily and rats in control group were only given distilled water.The rats were sacrificed on day 3,7,14,21 and 28,respectively,and pancreas were removed.The histological abnormalities were observed by electron microscope.The mRNAs of trans- forming growth factor?_1(TGF?_1)and procollagenⅠwere detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of TGF?_1 and?-smooth muscle actin(?-SMA)proteins was assessed by immunohistochemistry and the level of?-SMA protein was quantified by Western blot. Results In vitro,there existed AT_1 expression in PSCs,and Losartan reduced expression of collagenⅠ.Losartan treatment reversed the histological abnormalities observed by electron microscope,com- pared to treatment with distill water.The expression of?-SMA,TGF?_1 and procollagenⅠwere signifi- cantly higher in the control group than those in normal group and were reduced by Losartan to different extent in treatment group.Conclusion AT_1 antagonist can inhibit the activation and the profibrogenic action of PSCs by blocking AT_1 receptor-mediated pathways.

It is generally accepted that the inhibition of apoptosis is one of the mechanism of drug resistance to tumor. Members of the bcl-2 gene family are the most important regulators in apoptosis. The purpose of this study is to evaluate the value of expression of bcl-2 and bax gene in predicting the prognosis of acute leukemia patients, and to explore the relationship between bcl-2 and bax expression and drug resistance. Seventy patients with acute leukemia entered this study. Expressions of bcl-2, bax and mdr-1 gene were measured by RT-PCR method and FCM. The result showed that: bcl-2 had been widely detected in specimens of blood or bone marrow from acute leukemia patients, the expression levels were much higher than those in normal control (1.46 vs 0.71, P < 0.05), bax expression levels and bax/bcl-2 ratio in patients had no significant difference with the control. No relationships were found between the expression levels of bcl-2 and bax and AL patients' age, sex, platelet counts, hemoglobin levels, percentage of marrow blasts, FAB classification, and S + G(2)M%. Both Bcl-2 protein expression (34.6% vs 69.2%, P < 0.03) and bax/bcl-2 mRNA ratio (37.1% vs 82.9%, P < 0.01) were associated with response to therapy and CR rate, bax/bcl-2 ratio also influences the overall survival time. There was no relationship between bcl-2 and bax expression levels and mdr-1 expression levels.

Objective To find out the distribution pattern of environmental fluoride in the coal-burning endemic fluorosis areas to provide scientific evidence for establishing prevention and remedial measures in Chongqing. Methods According to historical data in Chongqing In 2008, 4 endemic villages(Lingyun and Lizi Villages of Wushan County, and Taiping and Daqing Villages of Pengshui County) and 2 non-endemic villages (ShuangLou and XianLong Villages of Yongchuan County) were investigated. Dental fluorosis of children in 8 to 12 year old and residents over 16 years of age for clinical skeletal fluorosis were examined in four endemic villages. Five households from each of 6 villages were taken, where 500 g of coal, mixed clay with coal, mixed coal of soil, coal cinder, soil were sampled; 15 people were taken in each village, each household gathering 500 g of corn, rice, potatoes, vegetables, grain and vegetable, 100 g of dried pepper and 250 ml of drinking water were sampled from 15 families of each village. Household drinking water samples were collected 1, each 250 ml. For those having tea-drinking habit, each household was collected 50 g of tea and 600 ml of drinking tea, the amount of fluoride were determined. Indoor and outdoor air was collected and measured in 5 households in each village. Results The detected rate of dental fluorosis of children in endemic areas was 74.65% (736/986). The detected rate of skeletal fluorosis of adult was 7.20%(736/986). The average fluoride content of coal, mixed clay with coal, mixed coal of soil, cinder coal, soil in the endemic villages was (310.56±209.46), (360.51±224.96), (293.62±65.15), (186.59±133.66), (497.54±294.70)mg/kg. The average fluoride content in non-endemic villages was (48.68±10.62), (275.66±62.69), (152.20±34.43), (209.14±188.66),269.98±58.21)mg/kg. The fluoride content level of endemic villages was significantly higher than that of non-endemic villages(t=7.67,31.54,5.82, 5.82, all P<0.05). The average fluoride content of drinking water, corn, pepper, flee, potato and vegetable in the endemic villages was (0.30±0.14)mg/L, (1.83±2.67), (23.50±91.80), (0.77±0.25), (0.44±0.11), (0.48±0.18)mg/kg, The average fluoride content in non-endemic village was (0.18±0.06)mg/L, (2.21±0.46), (2.82±2.51), (1.31±0.21), (0.64±0.41), (1.10±0.77)mg/kg. The fluoride content in drinking water and pepper in the endemic villages was significantly higher than that of the non-endemic villages(t=7.79, 2.33, all P<0.05). The fluoride content of rice, potato and vegetable in the non-endemic villages was significantly higher than that of the endemic villages(t=39.29,4.69,4.01, all P<0.05). There was no significant difference of fluoride content of tea and drinking tea between endemic villages[(99.41±55.83)mg/kg, (1.59±0.91)mg/L] and non-endemic villages[(79.95±43.78)mg/kg, (1.80±1.16)mg/L, t=1.01, 0.27, all P>0.05]. The amount of drinking tea in the endemic village[(1.45±0.68)L/d] was higher than that in non-endemic village[(1.00±0.47)L/d, t=4.27, P<0.05]. The average fluoride content of indoor air in the endemic village[(12.77±8.08)μg/m3] was higher than that in non-endemic village [(1.16±1.08)μg/m3, t=9.49, P<0.01]. There was no significant difference of fluoride content of outdoor air between endemic village and non-endemic village[(1.10±1.57), (0.39±0.31)μg/m3, t=2.01, P>0.05)]. Conclusions The fluoride source of coal-burning endemic fluorosis areas are coal and mixed coal of soil in Chongqing. Fluoride enters into human bodies mainly via respiratory, not from food. Although fluoride is rich in pepper, people don't eat it, so reducing the fluoride content in indoor air is the principle measure. Drinking tea may be was one factor of endemic fluorosis, which needs to be further studied.

OBJECTIVETo explore the method for establishing animal models of gouty nephropathy complicated with chronic renal failure.

METHODSSix-eight weeks old male Wistar rats were fed with 10% fodder yeast. The adenine at the daily dose of 100, 150, 200, 250, and 300 mg/kg was administrated to them by gastrogavage. The serum levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) were dynamically monitored. Meanwhile, the pathological changes of rat kidney were observed.

RESULTSCompared with the normal control group, serum BUN, Cr, and UA obviously increased in rats administered with 100 mg/kg for 7 days (P<0.05). Meanwhile, pathological changes as gouty nephropathy occurred. Along with the prolongation of the modeling time, the aforesaid biochemical indices and pathohistological changes of the kidney were more obvious. The blood Cr level just reached the chronic renal failure level on the 26th day of the administration (about the 4th week), and obviously exceeded the renal failure level on the 41st day (about the 6th week). The blood UA level increased to a higher level on the 7th day of modeling, and maintained at a higher level for a long time. It decreased rapidly from the 41st day to the 48th day. The renal pathological examination showed aggravated infiltration of lymphocytes and stromal fibrous proliferation. On the 48th day of modeling, the proliferation of the fibrous tissue and the interstitial fibrosis were obvious on the bases of the aforesaid changes. The serum BUN, Cr, and blood UA obviously increased in the rats administered with 150, 200, 250, and 300 mg/kg when compared with the normal control group, reaching the level of chronic renal failure (P<0.05). These levels obviously decreased 17 days after restoring to normal fodder feeding, and approached the normal levels till the 35th day.

CONCLUSIONIdeal experimental animal models of gouty nephropathy complicated with chronic renal failure could be established in male Wistar rats by feeding with 10% fodder yeast and 100 mg/kg adenine by gastrogavage for 5 weeks.

Animals ; Disease Models, Animal ; Gout ; complications ; Hyperuricemia ; Kidney Failure, Chronic ; etiology ; Male ; Rats ; Rats, Wistar ; Uric Acid ; blood

Objective To evaluate the effect of transcranial direct current stimulation (tDCS) on post-stroke dysphagia. Methods Cochrane Library (CENTRAL), Medline, EMBASE, CBMdisc, VIP, CNKI and WANFANG Digital Journals were searched to collect randomized controlled trials (RCTs) about transcranial direct current stimulation for post-stroke dysphagia until February 2018. Two researchers independently screened literature, extracted data and evaluated the quality of the included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of eight RCTs were screened, including 225 patients. Compared to the control group, tDCS was effective on post-stroke dysphagia (SMD=0.71, 95%CI: 0.32~1.10, P<0.001) with safety. Conclusion tDCS could improve swallowing function of post-stroke dysphagia. Due to the limited quantity and quality of the included studies, more high quality studies are needed.

BACKGROUNDCardiac resynchronization therapy (CRT) is a major breakthrough in therapy for advanced heart failure patients; however, a number of key clinical research questions remain, perhaps most importantly the issue of why apparently suitable patients do not respond to CRT.

METHODSSeven patients, six males and one female, aged (56.43 +/- 6.13) years, all diagnosed with dilated cardiomyopathy, were included in this study. They were all non-responders to CRT who underwent routine optimization postoperatively, and received optimal drug therapy. On the basis of biventricular pacing, titrating various atrioventricular (AV) intervals were performed to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction. Then, the effects of AV intrinsic conduction during CRT were evaluated.

RESULTSOn the setting of AV intrinsic conduction during CRT, the true fusional QRS complexes were the narrowest, and all patients showed alleviation of symptoms, improvement of exercise tolerance, life quality and hemodynamic parameters during more than 6 months of follow-up.

CONCLUSIONSTitrating AV intervals to get the true fusional QRS complexes composed of biventricular pacing and AV intrinsic conduction will be beneficial for non-responders to CRT. Maintaining AV intrinsic conduction during CRT may decrease the rates of non-responders to CRT.

Atrioventricular Block ; therapy ; Cardiac Pacing, Artificial ; Echocardiography ; Female ; Heart Failure ; therapy ; Humans ; Male ; Middle Aged ; Treatment Outcome

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.
Animals ; Dogs ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic System ; drug effects ; radiation effects ; Neutron Diffraction ; Recombinant Proteins ; administration & dosage ; pharmacology ; Survival Rate

OBJECTIVETo evaluate the effect of a 10-day course of triptolide (TP) on rat cytochrome (CY) P3A4 activity, and on the pharmacokinetics of cyclophosphamide (CPA).

METHODSIn the pharmacokinetics experiment, rats were orally given 0.9% NaCl solution (n=5) and TP [1.2 (mg/kg·d)] for 10 days and a single dose of CPA was administered intravenously (100 mg/kg) to rats on day 11. Blood samples were collected up to 4 h at predetermined time intervals, the plasma concentration of CPA was determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were determined. In the in vitro CYP3A4 activity inhibition research, rat blank liver microsomes were divided into 3 groups: a control group, a TS (5 μL, 200 μmol/L) with TP (5 μL, 12.5 μmol/L) group, a TS with ketoconazole (5 μL, 1 μmol/L) group. Concentration of 6β-hydroxylated testosterone (6β-OHT) in liver microsomes was measured by HPLC and the activity of CYP 3A4 was calculated through the following formula: Einhibitor/Econtrol × 100%=Cinhibitor/Ccontrol × 100%.

RESULTSCompared with the control group, the area under the plasma concentration-time curve (AUC0-∞) of CPA was significantly increased by 229.05% pretreated with TP (P<0.01). Peak plasma concentrations (Cmax) of CPA was significantly increased and plasma half-life was correspondingly extended. The CYP3A4 activity was significantly inhibited by ketoconazole 93.5%±0.2% and TP 84.6%±0.3% compared with the control group (P<0.01 and P<0.05, respectively).

CONCLUSIONOur results strongly suggested that long-term oral intake of TP can distinctly inhibit the CYP3A4 activity and this inhibition evidently decrease the formation of toxic metabolites of CPA.

Animals ; Cyclophosphamide ; pharmacokinetics ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; pharmacology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Herb-Drug Interactions ; Hydroxytestosterones ; metabolism ; Immunosuppressive Agents ; pharmacokinetics ; Injections, Intravenous ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; metabolism ; Phenanthrenes ; pharmacology ; Rats, Sprague-Dawley

UNLABELLEDTo study the clinical significance of the expression of antiapoptosis gene, survivin and bcl-2, and proapoptosis gene, Fas and bax, in acute myeloid leukemia (AML), RT-PCR was used to examine the expression of survivin and flow cytometry (FCM) to detect the expression of Fas, bcl-2, bax and bcl-2/bax ratio in 68 cases of AML. The results demonstrated that: (1) The positivity of survivin mRNA expression was significantly higher in AML compared to control (70.6% vs 30%, P < 0.05). (2) The expression of Fas and bcl-2 in AML before treatment was significantly higher than that in control (P < 0.001), but the bax expression did not (P > 0.05). (3) The survivin-positive AML cases showed a significantly lower Fas and higher bcl-2 expression in comparison with survivin-negative ones (P < 0.01 and P < 0.001, respectively), but the bax did not (P > 0.01). (4) Survivin-positive AML cases had a lower CR rate as compared with survivin-negative cases (64.6% vs 90%, P < 0.05). (5) The survivin-positive CR cases showed a decreased expression of Fas and bcl-2 after treatment in comparison with pretreatment expression (P < 0.001), but the bax expression remained unchanged before and after therapy. The survivin-positive NR cases showed a significantly decreased Fas and increased bcl-2 expression as compared with pretreatment expression (P < 0.001). bcl-2/bax ratio was also significantly higher in NR cases.

IN CONCLUSION70.6% AML cases showed positive for survivin expression with a lower CR rate, the survivin-positive AML showed a low Fas with high bcl-2 expression and bcl-2/bax ratio as compared to the survivin-negative cases.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; biosynthesis ; genetics ; Bone Marrow Cells ; drug effects ; metabolism ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; metabolism ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Neoplasm Proteins ; Proto-Oncogene Proteins ; biosynthesis ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; RNA, Messenger ; drug effects ; genetics ; metabolism ; bcl-2-Associated X Protein ; fas Receptor ; biosynthesis

OBJECTIVETo realize the influence of climatic changes on the transmission of hemorrhagic fever with renal syndrome (HFRS), and to explore the adoption of climatic factors in warning HFRS.

METHODSA total of 2171 cases of HFRS and the synchronous climatic data in Changsha from 2000 to 2009 were collected to a climate-based forecasting model for HFRS transmission. The Cochran-Armitage trend test was employed to explore the variation trend of the annual incidence of HFRS. Cross-correlations analysis was then adopted to assess the time-lag period between the climatic factors, including monthly average temperature, relative humidity, rainfall and Multivariate Elño-Southern Oscillation Index (MEI) and the monthly HFRS cases. Finally the time-series Poisson regression model was constructed to analyze the influence of different climatic factors on the HFRS transmission.

RESULTSThe annual incidence of HFRS in Changsha between 2000 - 2009 was 13.09/100 000 (755 cases), 9.92/100 000 (578 cases), 5.02/100 000 (294 cases), 2.55/100 000 (150 cases), 1.13/100 000 (67 cases), 1.16/100 000 (70 cases), 0.95/100 000 (58 cases), 1.40/100 000 (87 cases), 0.75/100 000 (47 cases) and 1.02/100 000 (65 cases), respectively. The incidence showed a decline during these years (Z = -5.78, P < 0.01). The results of Poisson regression model indicated that the monthly average temperature (18.00°C, r = 0.26, P < 0.01, 1-month lag period; IRR = 1.02, 95%CI: 1.00 - 1.03, P < 0.01), relative humidity (75.50%, r = 0.62, P < 0.01, 3-month lag period; IRR = 1.03, 95%CI: 1.02 - 1.04, P < 0.01), rainfall (112.40 mm, r = 0.25, P < 0.01, 6-month lag period; IRR = 1.01, 95CI: 1.01 - 1.02, P = 0.02), and MEI (r = 0.31, P < 0.01, 3-month lag period; IRR = 0.77, 95CI: 0.67 - 0.88, P < 0.01) were closely associated with monthly HFRS cases (18.10 cases).

CONCLUSIONClimate factors significantly influence the incidence of HFRS. If the influence of variable-autocorrelation, seasonality, and long-term trend were controlled, the accuracy of forecasting by the time-series Poisson regression model in Changsha would be comparatively high, and we could forecast the incidence of HFRS in advance.

China ; epidemiology ; Climate Change ; Forecasting ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; transmission ; Humans ; Humidity ; Incidence ; Models, Theoretical ; Seasons ; Temperature