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@#In this study, the formulation and preparation process of curcumin nanocrystalline injection were optimized to improve curcumin dissolution rate and bioavailability in vivo.Media grinding method was used to prepare curcumin nanocrystals, and the particle size was used as the evaluation index.The Box-Behnken experimental design was used to optimize its formulation and preparation process, and to characterize its physical and chemical properties.In addition, the dissolution of nanocrystal with different particle sizes was investigated by the paddle method, and the pharmacokinetics in rats were studied.The experimental results showed that the optimal formula and process were obtained through Box-Behnken experimental design, and that uniform curcumin nanocrystals with an average particle size of 223.1 nm were obtained.The results of X-ray diffraction and differential scanning calorimetry analysis showed that the crystal form was stable during the preparation of nanocrystals. In vitro dissolution experiments with different particle sizes showed that the dissolution rate and the degree of dissolution would increase if the particle size was smaller.Pharmacokinetic studies in rats showed that cmax and AUC0-∞ of curcumin nanocrystal injection were 4.9 and 4.1 times that of curcumin raw materials, respectively.In summary, the curcumin nanocrystal injection developed in this research have a stable preparation process and can significantly improve the dissolution rate and bioavailability of the drug, which provides some ideas for the research on curcumin preparation.
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Objective:To study the protective effects of different concentrations of curcumin on lung injury of rats in dry heat environment.Methods:Fifty Sprague-Dawley rats were randomly (random number) divided into five groups ( n = 10 each group): normal control group (NC), dry heat control group (DHC), and three different concentrations of curcumin pretreated dry-heat groups (50 mg/kg, 100 mg/kg, and 200 mg/kg). Rats in the NC and DHC groups were given a gavage of normal saline, and rats in the curcumin pretreatment groups were given a gavage of curcumin with different concentrations, once a day for 7 consecutive days. At 8th day, all groups except for the NC group were transferred to the climate cabin (The Simulated Climate Cabin for Special Environment of Northwest of China), with a temperature of (41 ± 0.5) and relative humidity of (10 ± 1)%. Rats in each group were anesthetized and sampled after reaching the state of heat stroke at 150 min, and same done to the NC group. Lung tissues were harvested and pathological changes were observed by HE staining. Lung wet/dry (W/D) weight ratio was detected and lung injury indicators such as total protein, white blood cell count and neutrophil count in bronchoalveolar lavage fluid (BALF) were also determined. Results:The lung injury pathology score, W/D weight ratio, total protein, white blood cell count and neutrophil count in BALF were the lowest in the NC group, and the highest in the DHC group, with significant difference ( P <0.01). With the increase of the concentration in the curcumin pretreatment groups, lung injury pathology score, W/D weight ratio, total protein, white blood cell count and neutrophil count in BALF were all declined. There were significant differences among the different concentration groups of curcumin and the NC and DHC groups ( P <0.01). Correlation analysis indicated that lung injury scores were correlated with W/D weight ratio of lung tissue, alveolar total protein content in BALF, white blood cell count, and neutrophil count (correlation coefficient r = 0.879, r = 0.935, r = 0.916, and r = 0.880, respectively, P <0.01). Conclusions:Pretreatment with different concentrations of curcumin can exert protective effects on lung injury of heat stroke rats in dry heat environment. Curcumin may have important clinical value in prevention and treatment of lung injury caused by heat stroke in dry heat environment.
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Hepatocellular carcinoma (HCC) is a common malignant tumor and patients with HCC often have liver cirrhosis, with an extremely high 5-year recurrence rate and poor prognosis even after curative treatment. In recent years, sarcopenia has attracted more and more attention as a poor prognostic factor for various malignant tumors; however, there is still a lack of studies on the association between skeletal muscle index and prognosis of HCC in China. Evidence in foreign countries has shown that sarcopenia may be an a negative prognostic factor for HCC patients. This article reviews the etiology and possible pathogenesis of HCC-related sarcopenia and related intervention measures including nutritional supplementation, appropriate physical exercise, and medication, in order to provide a reference for related studies in China.
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Objective? To?investigate?the?effects?of?different?doses?of?curcumin?on?the?levels?of?immune?factors?CD11b?and?CD19?in?peripheral?blood?of?heat?stroke?rats?in?a?simulation?dry-heat?environment.? Methods? 160?SPF??healthy?male?Sprague-Dawley?(SD)?rats?were?selected?and?divided?into?different?groups?according?to?random?number?table?method:?normal?saline?(NS)?control?group?(given?NS),?solvent?control?group?[given?sodium?carboxymethylcellulose?(CMCNa)],?and?curcumin?low,?medium?and?high?dose?pretreatment?group?(given?0.05,?0.10,?0.20?mg/g?of?curcumin+0.5%?CMCNa?solution).?There?were?32?rats?in?each?group,?and?were?challenged?only?by?10?mL·kg-1·d-1?lavage,?and?continuous?dosing?for?7?days.?On?the?8th?day,?rats?were?challenged?at?ambient?temperature?(41.0±0.5)?℃,?relative?humidity?(10±1)%?of?the?northwest?in?the?special?environment?of?artificial?lab,?placed?in?0?(normal?temperature),?50,?100?and??150?minutes?respectively.?The?levels?of?CD19?and?CD11b?in?peripheral?blood?of?each?rat?were?detected?by?flow?cytometry?instrument.? Results? With?the?extension?of?time?in?the?simulated?dry?and?heat?environment,?the?level?of?CD11b?in?peripheral?blood?was?gradually?increased?in?each?group,?and?the?peak?value?was?reached?at?150?minutes,?the?NS?control?group,?solvent?control?group?and?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?0.346±0.013,?0.342±0.013,?0.342±0.012,?0.325±0.012,?and?0.281±0.012,?respectively.?In?each?group,?the?level?of?CD19?was? first?increased?and?then?decreased,?reaching?its?peak?value?at?100?minutes,?and?the?level?of?the?NS?control?group,?solvent?control?group?and?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?0.586±0.010,?0.601±0.014,?0.684±0.009,?0.613±0.012?and?0.604±0.006,?respectively.?The?level?of?CD11b?in?the?curcumin?medium?and?high?dose?pretreatment?groups?were?significantly?lower?than?those?in?the?NS?control?group?and?solvent?control?group??(50?minutes:?0.237±0.011,?0.188±0.006?vs.?0.283±0.009,?0.289±0.012;?100?minutes:?0.260±0.010,?0.248±0.008?vs.?0.293±0.008,?0.290±0.007,?all?P?<?0.05),?and?after?placement?for?150?minutes,?the?level?of?CD11b?in?the?curcumin?high?dose?pretreatment?group?was?significantly?lower?than?that?in?the?NS?control?group,?solvent?control?group?and?curcumin?low?dose?pretreatment?group?(0.281±0.012?vs.?0.346±0.013,?0.342±0.013,?0.342±0.012,?all?P?<?0.05).?The?level?of?CD19?in?the?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?significantly?higher?than?those?in?the?NS?control?group?and?solvent?control?group?at?50?minutes?in?the?dry?and?hot?environment?(0.394±0.001,?0.436±0.009,?0.553±0.011?vs.?0.205±0.005,?0.197±0.003,?all?P?<?0.05),?at?100?minutes,?the?level?of?CD19?in?the?curcumin?low?dose?pretreatment?group?was?significantly?higher?than?that?in?the?NS?control?group?and?solvent?control?group?(0.684±0.009?vs.?0.586±0.010,?0.601±0.014,?both?P?<?0.05),?there?was?no?significant?difference?in?CD19?level?between?the?other?dose?pretreatment?groups?and?NS?control?group;?at?150?minutes,?there?was?no?significant?difference?in?CD19?level?between?the?curcumin?pretreatment?groups,?the?NS?control?group,?and?the?solvent?control?group.?The?peripheral?blood?immune?factors?CD11b?and?CD19?levels?in?the?NS?control?group?and?solvent?control?group?were?not?significantly?changed,?and?there?was?no?significant?difference?between?two?groups.? Conclusion? Curcumin?pretreatment?can?reduce?the?level?of?CD11b?and?increase?the?level?of?CD19?in?peripheral?blood?of?rats?with?dry?heat?stroke?in?the?early?and?middle?stages,?which?may?enhance?the?heat?resistance?and?prevent?the?occurrence?of?multiple?organ?dysfunction?by?increasing?the?body?immunity,?and?this?effect?has?nothing?to?do?with?the?dose?of?curcumin.
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Objective To observe the changes of potassium ion (K+), lactic acid (Lac) and glucose (Glu) in swine with traumatic hemorrhagic shock (THS) inside the dry-heat environment and to explore its possible mechanism. Methods A total of 40 local Landrace piglets were randomly(random number) divided equally into 4 groups: the normal temperature sham operation group (NS), the normal temperature traumatic hemorrhagic shock group (NTHS), the dry-heat sham operation group (DS group) and the dry-heat traumatic hemorrhagic shock group (DTHS). The experiment was carried out in the artifi cia climate cabin simulated the special environment of northwest of China. After exposed to their respective environment[dry-heat environment: (40.5±0.5), plus(10±2)% humidity; normal temperature environment: (25±0.5), plus(35±5)% humidity] for 3 h. Laparotomy were performed in swine of all groups, and then splenectomy and partial hepatectomy were performed only in NTHS and DTHS. The process of exsanguination from the external iliac artery was established to make the MAP reaching to 40-50 mmHg, and thus the traumatic hemorrhagic shock model of swine was successfully made. Blood samples were collected from external iliac artery at different intervals including the time just after exposure for 3 h and the successful establishment of traumatic hemorrhagic shock model (0 h) and then every 30 min after 0 h, serum levels of K+, Lac and Glu were detected. The features of varied serum K+, Lac and Glu were observed in each group. All data were statistically analyzed using One-way ANOVA and Pearson correlation analysis. Results After exposed , the level of serum K+inside the dry-heat environment was higher than that of swine inside the normal temperature group ( P<0.01), however the Glu level was lower in the swine inside dry-heat environment than that of swine inside the normal temperature ( P<0.01).The level of serum K+and Lac of DTHS group were rapidly increased from the establishment of the model to the death in about 3 h, while those of NTHS group were increased slowly. The level of K+and Lac were positively correlated in the two groups amd the correlation coeffi cient were rDTHS=0.927 (P<0.01) and rNTHS=0.539 (P<0.01),respectively. The level of Glu was progressively decrease in DTHS group, while in NTHS group, it was not noticeable. The level of K+and Glu were negatively correlated in the two group, the correlation coeffi cient were rDTHS=-0.804 (P<0.01) and rNTHS=0.420 (P<0.01),respectively. Conclusions The changes of serum K+, Lac and Glu occurred sooner and more obvious in traumatic hemorrhagic shock models inside dry heat environment (DTHS) group than those in NTHS group. The level of serum K+positively correlated with Lac, however, negatively correlated with Glu, which suggested that hyperkalemia and acidosis should be paid more attention to the treatment of traumatic hemorrhagic shock inside the dry heat environment, and the hypoglycemia should be treated at the same time.
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Objective:To study the characteristics of intestinal tract pathological injury of rats in hypobaric hypoxia at different high altitude.Methods:30 male SD rats were randomly divided into 5 groups:Plain group (n=6),High-altitude (HA) 5000 m for 10 day group(n=6),HA 5000 m for 21day group(n=6),HA 6500 m for 10day group(n=6),HA 6500 m for 21day group (n=6).Rats were raised normally either in plain or simulated high altitude environment,at the corresponding time point,rats were euthanized,small intestines were harvested,fixed tissues were processed routinely into paraffin and sections were stained routinely with hematoxylin and eosin.Morphologic parameters were measured by optical microscope and then the pathological injury score were evaluated.Results:The pathological injury scores ofjejunnm and ileum in the high altitude group were significantly higher than that of the plain group (P＜0.01),the pathological injury scores of jejunum,ileum and colon were significantly higher in the HA 5000 m for 21 day group than that of the HA 5000 m for 10 day group,but significant lower than that of the HA 6500 m for 21 day group,the pathological injury scores of jejunum,ileum and colon were significantly higher in the HA 6500 m for 10 day group than that of the HA 5000 m for 10 day group(P＜0.01,P＜0.05).The pathological injury scores of colon were significantly higher in the groups of the high altitude than the plain group except for the HA 5000 m for 10 day group (P＜0.01,P＜0.05).The pathological injury scores of jejunum had significant different with that of the colon in the HA 5000 m for 21 day group (P＜0.05);the pathological injury scores of both jejunum and ileum had significant different with that of the colon in the HA 6500 m for 21 day group(P＜0.05,P＜0.01).Conclusions:The injuries of the intestinal mucosa became serious with the with rising altitude and the stayed time,the intestinal injuries were more serious than that of colon at same situation,however there were no significant different between jejunum and ileum,the injuries of colon happened later than intestine,and they correlated with the stay time in the high altitude,which indicated that intestinal injury should be pay more attention in the early time of entering the hypobaric hypoxia environment of the high altitude.
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Heatstroke is a critical disease which usually catches in the hot environment in summer and abundant exercise that could bring about multiple organ dysfunction.The process of the occurrence and development of heatstroke includes of the compensatory phase,acute reaction stage and decompensation stage.The recent researches have shown that the mechanism of liver injury induced by heatstroke might be related to the direct action of heat,mitochondrial dysfunction in liver cells and cascade of inflammatory response,and each link promoted each other,finally caused liver injury.In addition,a cascade of inflammatory responses in the hepatic sinusoid might play a predominant role in liver injury induced by heatstroke.This paper aims to review the mechanism of liver damage caused by heatstroke in terms of the physiology and pathology,so as to provide perspectives for clinical prevention and treatment of liver injury.
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Objective To study the changes of oxidative stress and caspase-3 in swine with traumatic hemorrhagic shock in dry-heat environment of desert.Methods A total of 48 Landrace small swine were randomly(random number)divided into 2 groups(n=24 in each group), and then the traumatic hemorrhagic shock was established in room temperature environment and in dry-heat environmentin swine.Dry-heat environment traumatic hemorrhagic shock group (DHS), which was made in an artificial experiment cabin mimic the reality included swine exposed in the dry-heat environment of desert for 3 h (T0, n=6), T1 (50 min after shock modeling, n=6), T2 (100 min after shock modeling, n=6), T3 (150 min after shock modeling, n=6).At each interval, blood sample was collected to detect urea nitrogen (BUN) and creatinine, urine sample was collected to detect neutrophil gelatinase-associated lipoprotein (NGAL), kidney tissue samples were collected to evaluate renal morphological and tubular scores, as well as to detect catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA).Western blot was used to detect the level of caspase-3.Traumatic hemorrhagic shock group of room temperature environment (RTS) was established and variety of assays were carried out as same as those deteced in the dry-heat environment group.Results Compared with the room temperature environment exposed group,kidney damage index, antioxidant and caspase-3 were increased in desert dry-heat environment exposed for 3 h group, but there were no statistically significant difference(P> 0.05).And from T1 then on, the levels of NGAL, CAT and SOD in DHS groups were increased which were significant different from those in RTS group (P<0.05 or P<0.01).There were significant differences in BUN and creatinine at T2 between two groups(P<0.05).At T3, caspase-3 protein content in DHS group was significantly different from that in RTS group (P<0.01).Correlation analysis showed that the NGAL level was correlated with the levels to MDA (rRTS=0.935, rDHS =0.858, P<0.01) in RTS group and DHS group.Compared with RTS group, renal tissue under light microscope showed that Bowman appeared dilated with degeneration and exfoliated epithelial cells, proximal tubule epithelial shedding, and interstitial edema in DHS group.Electron microscope showed that mitochondria became pleomorphic, endoplasmic reticulum with fold broadening.Conclusions When traumatic hemorrhagic shock happened in the desert dry-heat environment, desert dry-heat environment can aggravate kidney damage, possibly by reducing the renal tissue antioxidant enzyme content and increase renal tissue caspase-3 activity to promote renal tissue apoptosis.Antioxidant stress and apoptosis may be an important role in the prevention of the secondary kidney injury induced by traumatic hemorrhagic shock in dry-heat environment.
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Objective To investigate the expression of circulating microRNA (miRNA) of rats with hypobaric hypoxia‐induced pulmonary hypertension (HPH) .Methods Commercial rat miRNA microarray was employed to detect and analyze the circulating miRNA profile in the serum samples of Sprague‐Dawley rats with hypobaric hypoxia‐induced HPH and controls .Furthermore ,differentially expressed candidate circulating miRNAs between HPH and control groups were validated by Real‐time quantitative PCR based on the case‐control study ,and receiver operating characteristic curve (ROC ) analysis was used to test the performance of four differentially expressed circulating miRNAs in discriminating HPH and control groups .Results Compared with those in the control group ,13 upregulated miRNAs and 10 downregulated miRNAs were identified in hypobaric hypoxia‐induced HPH rats by using miRNA microarray . And differentially expressed miR‐451 , miR‐505 , let‐7d and miR‐214 were validated by using RT‐PCR .ROC analysis showed that the area under the curve of miR‐451 ,miR‐505 and let‐7d was 0 .979 ,0 .938 and 0 .993 in discriminating HPH and control groups ,respectively .Conclusion The aberrant expression of circulating miR‐451 ,miR‐505 and let‐7d in serum may be correlated with the pathogenesis of HPH .
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Objective To study the application of small interfering RNA silencing S100A4 protein in human gastric cancer cell BGC-823 proliferation,apoptosis and the effect of chemotherapy sensitivity.Methods Human gastric carcinoma cell line BGC-823 transfection siRNA,RT-PCR detected the changes of mRNA after transfection.Groups divided into interference group,negative control group and normal control group.MTT test determined different concentrations of oxaliplatin in gastric cancer cells and calculated IC50,then draw cell growth curve,TUNEL method to detect apoptosis,RT-PCR tested each cell mRNA changed,Western blot detected the change of the S100A4 protein.All data analysis by SPSS17.0,t test applied,RT-PCR and Western blot results analysis by SPSS17.0,comparing multiple samples by using single factor analysis of variance and LSD test.P ＜ 0.05 was statistically significant.Results RT-PCR results showed that BGC-823 cell transfection,S100A4mRNA expression quantity respectively after 48 hours:(0.674+0.011),(0.652+0.021),(0.345 + 0.040),the interference group and normal control group were statistically significant (P =0.012,P ＜ 0.05) and the negative control group with interference group differences were statistically significant (P =0.000,P ＜ 0.05),and normal control group was no statistically significant difference with the negative control group (P =0.380,P ＞ 0.380);Western blot results showed BGC-823 cell transfection S100A4 expression significantly lowered respectively after 48 hours,there were (0.654 + 0.025),(0.642 + 0.014),(0.317 ± 0.061),the interference group and normal control group was statistically significant (P =0.01,P ＜ 0.05),between negative control group and interference group were statistically significant (P =0.000,P ＜ 0.05),normal control group and the negative control group had no significant difference (P =0.341,P ＞ 0.341).After S100A4-siRNA transfection,gastric carcinoma BGC-823 cell proliferation decreased,TUNEL method showed obviously increase apoptosis,MTY showed that IC5o of oxaliplatin was 56.31 μmol/L,after transfection,IC50 was 0.654 μmol/L.Conclusions This study showed that the siRNA silence S100A4 protein inhibit gastric cancer cell proliferation,induced apoptosis and improved chemotherapy sensitivity of oxaliplatin.S100A4 might be prompt targets for the treatment of gastric carcinoma.
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Experimental pathology is an important part of life science research associated with animal experiment. Acquisition and fixation of optimum specimen and subsequent section of paraffin embedded tissue and dyeing are key factors playing important role in reliability, authenticity of pathological diagnosis.This paper summarizes the problems encountered in pathological section making of animal experiment and it correspond solutions.
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Objective To investigate the effect of Curcumin on rats with severe acute pancreatitis associated renal injury and explore the possible mechanisms.Methods A total of 72 rats were randomLy divided into sham-operated group(S group, n =24), severe acute panceratitis with renal injury group(M group, n =24) ,Curcumin-treated group(Cur group,n=24).The S and M groups were given 1.5 ml saline through intragastric administration 3 hours before operation,while the Cur group was fed with same amount of Curcumin diluent(200 mg/kg).The pancreas and pancreatic tail-segment was dissociated and the head of pancreas was occlused in rats to form the model,blood vessel forceps was loosed after 3 hours.All the rats were sacrificed at 12 h,24 h, 36 h and 48 h after modeling.The level of ascites, serum amylase, creatinine, blood urea nitrogen were detected and the pathological chang of pancreas was observed under light microscope.Take the right kidney for Superoxide Dismutase (SOD) determination and the expression of hypoxia inducible factor-1αmRNA in the right kidney was detected with realtime polymerase chain reaction (RT-PCR).Results Compared with Cur group, the level of ascites, serum amylase, creatinine, blood urea nitrogen in M group were significantly increased, but the activity of SOD, the express of hypoxia inducible factor-1αmRNA had a significant decline (P＜0.05).The tissue damage of pancreas and the kidneys became more serious.But a better performance was to be found in the function of the Cur group's kidney and pancreas, and the the difference was statistical significance (P ＜0.05).Conclusion Curcumin has a good protective effect on severe acute pancreatitis associated renal injury.It may be through up-regulation expression of HIF-1α mRNA and increase the activity of superoxidase dismutase, then reduce the cell apoptosis and necrosis of the kidney, improve the ability of the kidney to tolerate hypoxia.
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Objective To study the pathological changes and expressions of NO and iNOS mRNA in the lung tissue of traumatic hemorrhagic shock rats under dry heat environment of desert and their relations to the lung injury.Methods A total of 140 male SD rats were randomly (random number) ivided into the room temperature (25 ℃) environment traumatic hemorrhagic shock group (room temperature group) and the dry heat traumatic hemorrhagic shock groups (dry heat group,temperature 40℃,humidity 10％),respectively,and each groups was further randomly divided into 7 subgroups:the control subgroup,post shock subgroups at 0,0.5,1,1.5,2and 3 h (n =10 in each subgroup).The rats of control subgroup were not treated,and rats of dry heat group were placed in dry heat environment for 60 min,then anesthetized,fixed,and insertion of intravenous indwelling needles and catherization of right carotid artery,jugular vein and the right femoral artery were performed.After stabilization for 10 min,2500 g iron wheel was used to be dropped from 30 m height and vertically hit the upper left femoral of SD rats in order to make comminuted fracture,wounds were quickly dressed after injury.Exsanguination from right femoral artery was kept until MAP maintained at (35 ± 5) mmHg,and resuscitation was carried out after continue monitoring for 60 min.After the establishment of traumatic hemorrhagic shock model in each environment,the rats were sacrificed at given intervals,and thoracotomy was performed to take broncho-alveolar lavage fluid (BALF) and lung tissue.Pathological changes of lung tissues were observed by using HE staining and NO concentration of lung tissue was detected by one-step method,and changes of the iNOS mRNA expressions were detected by using fluorescence quantitative PCR.Then t test,ANOVA and Pearson correlation analysis were used for the data analysis.Results The pathological change in dry heat group at each interval was more severe,and pulmonary histopathological injury score was higher,and the protein exudation was more profuse compared with the room temperature group.NO concentration in lung tissue homogenate of dry heat group was higher than that of room temperature group (t =2.472,P ＜ 0.05),and the difference in NO level between different intervals within the dry heat group was statistically significant (F =6.77,P ＜ 0.01).The NO concentration in dry heat group reached its maximum at 2 h (3.35 ± 0.23) μmol / g and the peak value emerged sooner than that in room temperature group.The difference was statistically significant in overall expression of iNOS mRNA between two groups analyzed with t test (t =3.619,P ＜ 0.01),and there was statistically significant difference between intervals within the dry heat group (F =12.34,P ＜0.01).The values of iNOS mRNA in the dry heat group were higher than those in the room temperature group at the same given intervals,and the peak value appears at 1.5 h in dry heat group,and the room temperature group it began to increase at 2 h.The concentration of NO and the expression of iNOS mRNA were positively correlated with each other in two groups (r =0.680,r =0.376).The expression of iNOS mRNA and lung histopathological injury score was positively correlated in two groups (r =0.846,r =0.899).Conclusions When traumatic hemorrhagic shock occurred in the dry heat desert environment,the lung injury was more severe and appeared sooner than that in the room temperature environment.NO and iNOS played important roles in the secondary lung injury in the wake of traumatic hemorrhagic shock in rats under the dry heat environmengt of desert.
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Objective To explore the value of combined detection with MMP-9 and uPA in the progno-sis of pancreatic carcinoma. Methods By immunohistochemistry PV methods,the expression of MMP-9 and uPA was respectively studied in 63 surgical specimens of primary pancreatic carcinoma and the survival time of patients with pancreatic carcinoma was analysed. Results The expressions of MMP-9 and uPA were positively related(r=0. 573,P=0. 000). The expression of MMP-9 and uPA significantly correlated with differentiation (r= -0. 271,P=0. 032;r= -0. 333,P=0. 008),TNM stages(r= -0. 449,P=0. 000;r= -0. 430,P=0. 000)and lymph node metastasis(r=0. 329,P=0. 009;r=0. 400,P=0. 001),separately. The expression of MMP-9 had also a significant correlation with tumer size(r= -0. 297,P=0. 018)and distant metastasis(r=0. 320,P=0. 011). Univariate analysis identified that tumor size(χ2 =8. 766,P=0. 012),differentiation(χ2 =29. 050,P=0. 000),clinical stage(χ2 =24. 940,P=0. 000),distant metastasis(χ2 =12. 846,P=0. 000), lymph node metastasis(χ2 =15. 457,P=0. 000),MMP-9(χ2 =32. 700,P=0. 000)and uPA(χ2 =41. 495,P=0. 000)were significantly associated with prognosis. Kaplan-Meier survival analysis showed that 1-year survival rate of patients with MMP-9 ( -),uPA ( -)were significantly longer than that of the patients with MMP-9( ﹢),uPA( ﹢),respectively(χ2 =32. 700,P=0. 000;χ2 =41. 495,P=0. 000);1-year survival rate of patients with MMP-9( -)/uPA( -)was significantly longer than the others( Log-rank test,χ2 = 54. 892, P=0. 000). COX regression revealed that differentiation(RR=2. 315,P=0. 004),clinical stage(RR=1. 694, P=0. 002),MMP-9(RR=0. 165,P=0. 000)and uPA(RR=0. 244,P=0. 007)was independent prognostic factors in pancreatic carcinoma. Conclusion They may have a synergistic function in the the process of growth and invasion in pancreatic cancer between MMP-9 and uPA,and the posssible mechanism is that uPA activate degradation of MMP-9,which is not favorable to prognosis. Combined analysis of MMP-9 and uPA may lead to a more reliable prognostic estimation,as the beneficial supplement of the differentiation,and clinical stage to judge the prognosis of pancreatic cancer.
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ObjectiveTo investigate the changes in characteristics of blood gas analysis of heatstroke rats residing in dry-heat environment of desert, and to provide a theoretical reference for its treatment in clinic.Methods Forty-eight male Sprague-Dawley (SD) adult rats under anesthesia were divided into six groups by random number table, with 8 rats in each group: namely mild, moderate, severe heatstroke groups and their corresponding control groups. The rats were placed in an artificial chamber with simulated desert dry-heat environment (temperature 41℃, humidity 10%) for about 70, 110, 145 minutes, respectively, to reproduce mild, moderate, severe heatstroke models. The rats in control groups were placed in a normothermic environment for corresponding duration. Abdominal aorta blood of each group was collected for blood gas analysis, and electrolytes were determined by a portable blood gas analyzer.Results① Arterial partial pressure of carbon dioxide (PaCO2) in mild heatstroke group was increased to (45.64±8.19) mmHg (1 mmHg = 0.133 kPa), arterial oxygen saturation (SaO2) was decreased to 0.84±0.08, pH value was lowered to 7.36±0.11, showing that respiratory acid-base imbalance was resulted. Base excess of extracellular fluid (BEecf) in moderate heatstroke group was decreased to (-3.00±0.76) mmol/L, HCO3- was decreased to (19.39±1.89) mmol/L, and pH value was lowered to 7.21±0.07, indicating that metabolic acid-base imbalance was aggravated gradually. The changes in parameters in severe heatstroke group gradually became more serious, and a significant difference was found as compared with those of mild and moderate heatstroke groups (PaCO2:F = 6.537,P = 0.006; SaO2:F = 5.174,P = 0.015; pH value:F = 10.736,P = 0.001;BEecf:F = 67.136,P = 0.000; HCO3-:F = 5.612,P = 0.011), manifesting an obvious combination of respiratory acidosis and metabolic acidosis, and a serious mixed acid-base disturbance was produced.② Compared with corresponding control groups, hemoglobin (Hb) was significantly increased in moderate heatstroke group (g/L: 15.31±1.84 vs. 13.28±0.94,t = 2.791,P = 0.014), Hb and hematocrit (HCT) in severe heatstroke group were significantly increased [Hb (g/L): 16.59±2.52 vs. 13.42±1.15,t = 3.224,P = 0.006; HCT: (53.50±6.63)% vs. (45.50±4.47)%,t = 2.828, P = 0.013], showing that the degree of dehydration was aggravated gradually from mild to serious degree.③ Serum sodium content in mild heatstroke group was normal (t = 0.665,P = 0.517), serum potassium content was lowered significantly (t = -2.526,P = 0.024); serum sodium content in moderate heatstroke group was increased significantly (t = 2.162,P = 0.048), serum potassium content was lowered significantly (t = -5.458,P = 0.000); and serum sodium content in severe heatstroke group rose obviously (U = 12.500,P = 0.038), and most of the rats showed hypokalemia, with a small proportion of rats showed obvious hyperkalemia (U = 19.500,P = 0.195).ConclusionsAcidosis, electrolyte disturbance, respiratory failure and dehydration in heatstroke occurred in dry-heat environment of desert. It indicates that resuscitation should focus on correction of respiratory acidosis, with simultaneous correction of metabolic acidosis, and one should be alert to correct dehydration and electrolyte disturbance. During the moderate phase and the serious phase, correction of aggravated metabolic acidosis should be reinforced, and the prevention and treatment of the severe dehydration and electrolyte disturbance should be undertaken actively.
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Objective To investigate the effect of rhodiola on severe acute pancreatitis associated renal injury and explore the potential mechanisms.Methods A total of 90 rats were randomly divided into sham-operated group (S group,n =18),severe acute pancreatitis with renal injury group (M group,n =18),low rhodiola dose group (3 g/kg,T1 group,n =18),moderate dose rhodiola group (6 g/kg,T2 group,n=18),high rhodiola dose group (9 g/kg,T3 group,n =18).The S and M groups were given 6 g/kg saline through intraperitoneal injection before operation while the T1 group,T2 group and T3 group were given with 3 g/kg,6 g/kg,9 g/kg dose of rhodiola through intraperitoneal injection,respectively.The pancreas was dissected and the head of pancreas was occluded by blood vessel forceps for 3 hours to make rat model.All the rats were sacrificed at 12 h,24 h,36 h after modeling.The level of ascites amylase,serum amylase,creatinine,blood urea nitrogen,interleukin 1β(IL-1β) and interleukin 10 (IL-10) were detected and the pathological change of pancreas and the left kidney was observed under light microscope.The serum levels of IL-1β and IL-10 were detected by enzyme-linked immunosorbert assay (ELISA).Take the right kidney for superoxide dismutase (SOD) determination and the expression of hypoxia inducible factor-1α (HIF-1α)mRNA in the right kidney was detected by real-time polymerase chain reaction (RT-PCR).Results Compared with the S group,the level of serum amylase,creatinine,blood urea nitrogen and IL-1β in M group increased significantly,but the activity of SOD has a significant decline (P ＜ 0.05).Compared with M group,the level of serum amylase,creatinine,blood urea nitrogen and IL-1 β in T2 group has a significant decline,but the activity of SOD,the express of HIF-1α mRNA and IL-10 has a significant increase (P ＜ 0.05).With the dose of rhodiola increased,the renal and pancreatic function in T2 group had a better performance than T1 group,and the difference was statistical significant (P ＜ 0.05).But compared with T2 group,the renal and pancreatic function in T3 group did not increased significantly (P ＞ 0.05).Conclusions Moderate dose of rhodiola (6 g/kg) has a good protective effect on severe acute pancreatitis associated renal injury.It may be associated with the inhibitory expression of IL-1β,up-regulated expression of IL-10,HIF-1α mRNA,and the increased activity of SOD.So it can then reduce cell apoptosis and renal necrosis,and improve the ability of the kidney to tolerate hypoxia.
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Objective To observe the function of kidney compromised and histopathological changes of renal tissue in heatstroke rats under the dry-heat atmosphere of desert in order to find the mechanism for provide a rationale of clinical treatment.Methods Forty-eight anaesthetized rats were divided into six groups (n =8 in each group):mild heatstroke group with its control group,moderate heatstroke group with its control group,and severe heatstroke group with its control group.The rats of three heatstroke groups were placed in a dry-heat environment prolonged with 41 ℃ and 10％ humidity,and the three control groups were placed in a room temperature prolonged with 25 ℃ and 35％ humidity.At heatstroke status of each group,arterial blood samples were collected from each group for testing creatine kinase (CK),creatinine (CREAT),uric acid (UA) and urea,kidney tissues and muscle tissues were taken for pathological examinations.Results Pathological examination showed dilatation and congestion of vessels,thrombosis,bleeding,protein casts and endothelium injury were found in the heatstroke rats.In mild heatstroke,the pathological changes mainly manifested as dilatation and congestion of vessels ; in moderate one,the changes mainly manifested as thrombosis; and in severe one,changes mainly manifested as bleeding and protein casts.Muscle tissues presented rhabdomyolysis,especially in severe one.The differences in biomarkers between three different degrees of heatstroke showed statistical significance (CK:F =136.204,P =0.000;CREAT:F =172.865,P=0.000; UA:F=546.454,P=0.000; urea:F=73.823,P=0.000).There was no significant difference in UA between mild heatstroke group and its control group (t =1.943 ;P =0.072),and the differences in rest biomarkers showed statistical significance between each heatstroke group and its control group (P =0.000).Conclusions The kidney injury developed during heatstroke in dry-heat environment of desert suggests that we should be alert to disseminated intravascular coagulation (DIC),myolysis and acute kidney failure,and should monitor the blood biochemical changes closely and treat it energetically,rescuing a heatstroke patient in dry-heat environment of desert.
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Objective The extremely xerothermic environment of desert easily causes heatstroke and consequently multiple organ damage.Few reports are seen at home and abroad on heatstroke-induced lung injury associated with dry heat of desert.This stud-y explored the changes of the injured lungs in heatstroke rats in xerothermic desert. Methods Forty-eight male SD rats were ran-domly divided into six groups of equal number: mild, moderate and severe heatstroke groups and their corresponding controls.The rats of the three heatstroke groups were exposed to a temperature of 41 ℃and humidity of 10%, while those in the three corresponding control groups to a temperature of 25 ℃ and humidity of 35% for 70, 110 and 145 minutes, respectively.Then all the rats were sacrificed and the bronchoalveolar lavage fluid ( BALF) and lung tissues were collected for observation of pathological changes, obtainment of lung in-jury scores, calculation of the wet/dry weight ratio of the lungs, measurement of the total protein level in the BALF, and determination of the malondialdehyde ( MDA) content in the lung tissue. Results The mild, moderate and severe heatstroke groups showed re-markable increases compared with the three corresponding control groups in lung injury scores (3.25 ±0.50, 6.50 ±0.58 and 8 ± 0.82 vs 1.25 ±0.50, 1.00 ±0.00 and 1.25 ±0.50), the wet/dry weight ratio of the lungs (3.50 ±0.57, 4.85 ±0.19 and 4.10 ± 0.07 vs 1.78 ±0.66, 1.67 ±0.68 and 1.67 ±0.25), the total protein level in the BALF ([93.51 ±5.54], [141.24 ±6.07] and [160.76 ±6.74] μg/mL vs [42.6 ±8.67], [45.25 ±6.78] and [41.68 ±3.62] μg/mL), and the content of MDA in the lung tis-sue ([1.79 ±0.08], [2.79 ±0.11] and [3.52 ±0.36] nmol/mg prot vs [1.21 ±0.12], [1.20 ±0.12] and [1.28 ±0.19] nmol/mg prot) .The lung injury scores, the total protein level in the BALF, and the content of MDA in the lung tissue were increased with the prolonging of the time of exposure to dry heat, while the wet/dry weight ratio of the lungs was the highest in the moderate heat-stroke group.The lung injury scores were positively correlated with the wet/dry weight ratio of the lungs, the total protein level in the BALF, and the content of MDA in the lung tissue (P<0.01). Conclusion Heatstroke in the xerothermic environment of desert can cause lung injury in rats, which deteriorates with the prolonging of the time of exposure to dry heat.As for the management of such heatstroke, more attention should be paid to the protection against lung injury.
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This paper introduces the structure and the equipment of special artificial environmental and experimental chamber and its basic operating requirements. In compliance with the national standard and safety management, the safety, effectiveness and controllability of the chamber are described.
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Objective To investigate the siRNA interference of S100A4 mRNA of human pancreatic cancer cell radiosensitivity.Method Cultured human pancreatic BxPC-3,AsPC-1 in vitro,logarithmic phase cells as the experimental object,were divided into three groups:normal control group (without any treatment),negative control group (transfected with negative control fragment),interference group (transfected S100A4 protein fragment siRNA),the chemical synthesis siRNAS100A4 fragment interference of S100A4 mRNA 0,1,2,3,5,7,10 Gy given 6MV X-ray irradiation,the use of clone formation assay,Giemsa stained colony formation rate is calculated and SF2,and the fitting cell survival curve.Results The siRNA interference S100A4 after BxPC-3 cells SF2 value are:the control group 0.68±0.02,negative control group 0.65±0.01.interference group,0.38±0.02,P＜0.05.AsPC-1 cells SF2 value:control group 0.48±The0.02,negative control group 0.47±0.02; interference group:0.37±0.04,P＜0.05.Conclusion siRNA interference S100A4 after increased radiosensitivity of human pancreatic cancer cell lines.