Résumé
Objective:To investigate the clinical efficacy and prognosis of sacubatrovalsartan combined with dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF).Methods:Totally 206 consecutive patients with HFrEF in our hospital from March 2021 to September 2021 were enrolled and randomly(random number) divided into the control group ( n = 51), the sacubatrovalsartan group ( n = 52), the dapagliflozin group ( n=51) and the combined treatment group ( n= 52). The baseline clinical data of patients and laboratory examination results were collected. The changes of related results before and after treatment in each group were analyzed and compared. After discharge, the enrolled patients were followed up by outpatient or telephone for an average of 6 months to determine whether the patients had heart failure rehospitalization, ventricular arrhythmia, major adverse cardiovascular events (MACE), etc. Results:After anti-heart failure treatment, there were significant differences in NT-proBNP, left ventricular ejection fraction (LVEF) and soluble growth stimulating gene 2 protein (ST2) among the four groups. NT-proBNP and ST2 in the combined treatment group were significantly lower than those in the other groups, and LVEF was significantly higher. Compared with the control group, the rehospitalization due to heart failure and MACE events in the other three groups were significantly lower ( P < 0.05), and the combined treatment group had the lowest ( P < 0.05). The Kaplan-Meier survival curve showed that the survival probability of the other groups was significantly higher than that of the control group, and was the highest in the combined treatment group. Conclusions:The clinical efficacy and prognosis of HFrEF patients could be significantly improved after the treatment of sacubatrovalsartan combined with dapagliflozin.
Résumé
This study explores the differential protein expression in the colorectal cancer (CRC) patients to validate a new biomarker for tumor progression. CRC tissues and their adjacent non-cancerous tissues were analyzed by two-dimensional LC/MS/MS. Nucleophosmin 1 (NPM1) was selected and confirmed its differential expression by Western blot. Immunohistological staining of NPM1 in tissues was performed to validate its correlation with clinicopathologic parameters of CRC patients. There were 39 candidates with significant difference between cancerous tissues and their adjacent non-cancerous tissues, which included 19 increased proteins and 20 decreased proteins in CRC samples. Especially, NPM1 was correlated with poor differentiation, and lymph node metastasis according to the analysis of patients’ clinicopathologic parameters. Increased expression of NPM1 can be as a critical biomarker for clinical diagnosis of tumor progression of CRC patients.
Résumé
Objective To evaluate left ventricular myocardial systolic function in patients with obstructive sleep apnea hypopnea syndrome ( OSA HS) with normal left ventricular ejection fraction( LVEF) using three‐dimensional strain echocardiography . Methods One hundred patients with OSA HS were divided into mild group ,moderate group and severe group according to apnea hypopnea index ( A HI) w hile matched with 32 healthy people as control group . T he parameters such as three‐dimensional LVEF ,global longitudinal strain( GLS) ,global circumferential strain( GCS) ,global area strain( GAS) ,global radial strain ( GRS) ,twist and torsion based on standard three‐dimensional echocardiography were measured by three‐ dimensional strain echocardiography , the above parameters among the four groups were compared for difference .Linear correlationship between A HI ,LVEF and the three dimensional strain parameters was analyzed respectively . Results ①T here was no significant difference in three‐dimensional LVEF ,twist and torsion between each groups( P >0 .05 ) . ②GLS ,GAS and GRS were lower in mild ,moderate and severe group compared with control group ,decreasing along with the disease severity ( P <0 .01 or P < 0 .05 ) . GCS in severe group was lower than that in control group ( P <0 .01 ) . ③GLS and GAS in severe group were lower than those in mild group ( all P <0 .05) .GRS in moderate and severe group were lower than that in mild group( all P < 0 .05 ) ,GAS ,GRS in severe group was lower than those in moderate group ( P <0 .05) . ④T here was a mild correlation between GLS and A HI ( r =0 .342 , P <0 .01) ,GAS and A HI ( r=0 .294 , P <0 .01) ,GRS and A HI ( r = -0 .411 , P <0 .01 ) . T here was a mild correlation between GCS and three‐dimensional LVEF ( r= -0 .354 , P <0 .01 ) ,GAS and three‐dimensional LVEF ( r = -0 .326 , P <0 .01) ,GRS and three‐dimensional LVEF ( r =0 .300 , P <0 .01) . Conclusions T he left ventricular myocardial systolic function is impaired in all patients with OSA HS even with normal LVEF and the dysfunction is aggravating with the disease severity . Ultrasonic three‐dimensional strain imaging technology can be used to detect the subclinical myocardial systolic dysfunction quantitatively in the early stage of OSA HS patients .
Résumé
Objective?To evaluate the application of guidewire-assisted biopsy and balloon dilatation cytology smear through ERCP in diagnosis of patients with hilar cholangiocarcinoma.?Methods?During the ERCP procedure, 52 patients with hilar cholangiocarcinoma were treated with balloon dilatation, and cytology smear from the surface of the balloon. At the same time, biopsy forceps assisted by guidewire inserted into the bile duct to biopsy the lesion and obtain specimens.?Results?Success rate of obtaining histopathological through ERCP guidewire assisted biopsy in biliary bile duct was 100.0%, 31 cases were histological diagnosed by forceps biopsy in 52 cases, positive diagnosis rate was 59.6%; The patient with balloon dilatation in 52 cases give cytology smears obtained diagnosis in 22 cases, the positive rate was 42.3%; cytology smear combined with biopsy, a total of 34 cases were diagnosed, the positive rate was 65.4%. There was no serious complications occurred.?Conclusion?Biopsy assisted by guidewire through ERCP is a safe, simple, easy technique and an effective means of obtaining pathological, meanwhile, the cytology smear after balloon dilatation can be used as a supplement to biopsy, and provides an effective means in pathological diagnosis of hilar cholangiocarcinoma.
Résumé
Objective To observe air disinfection efficacy of ultraviolet ray,ozone disinfector,and circulating air disinfector in outpatient blood collection room.Methods Air in outpatient blood collection room was disinfected by ultraviolet ray,ozone disinfector,and circulating air disinfector,air specimen was taken before and after air disinfection,as well as after 1,2,3,and 4 hour working condition of staff,efficacy of 3 disinfection methods were compared.Results Under static condition,there was no significant difference in average colony forming unit(CFU) among 3 disinfection methods(P =0.317),the average CFU in air which disinfected by ultraviolet ray and ozone disinfector increased rapidly after the entry of personnel,the number of air colony did not meet the requirements of category Ⅲ environmental sanitation standard after staff worked for 2 hours;circulating air disinfector could continuously disinfect after the entry of personnel,the average CFU met the requirement of category Ⅲ environmental sanitation standard after staff worked for 1,2,3,and 4 hours;there were significant difference in the CFU among different disinfection methods(F =211.00,P<0.001),there were significant difference in CFU at different sampling time(F =272.95,P< 0.001).Conclusion Circulating air disinfector can meet the requirements of category Ⅲ environmental sanitation standard during the working condition of staff,and is suitable for air disinfection in outpatient blood collection room.
Résumé
Objective: To investigate the effects of butanol extract from Paris polyphylla var. yunnanensis (BEPP) on the biofilm formation of Candida albicans in vitro. Methods: Microdilution method was used to determine the minimum inhibitory concentration (MIC). XTT assay was used to determine the SMIC80. Flat band method was used to protract the time-kill curve. Scanning electron microscopy (SEM) was used to observe the morphological changes of the biofilm. Confocal laser scanning microscopy (CLSM) was used to detect the thickness of the biofilm. The quantification real-time PCR (qRT-PCR) was used to detect the expression changes of genes (EAP1, MP65, and SUN41) of the biofilm cells. Results: The MIC of BEPP against C. albicans strains was determined as 32-128 μg/mL. The SMIC80 of BEPP against the biofilm of C. albicans strains was determined as 128-512 μg/mL. Time-sterilization curve results indicated that BEPP had a promise bactericidal effect. SEM results showed that the formation of C. albicans biofilm was inhibited by BEPP, and the morphology of biofilm was also affected by BEPP. The thickness of C. albicans biofilm was reduced by BEPP according to CLSM results. Furthermore, qRT-PCR results indicated that expressions of EAP1, MP65, and SUN41 were significantly down-regulated by BEPP. Conclusion: Our results demonstrate that BEPP inhibits the biofilm formation of C. albicans in vitro.
Résumé
<p><b>OBJECTIVE</b>To investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) , alone and in combination with fluconazole (FLZ) on FLZ-resistant Candida albicans.</p><p><b>METHOD</b>The minimum inhibitory concentrations (MIC) and sessile MIC80 (SMIC80) of EAHD and FLZ to FLZ-resistant C. albicans were determined by CLSI M27-A3 microdilution method, and the synergy of EAHD combined with FLZ were examined by the checkerboard microdilution assay. Agar plate-method was adopted to observe the rate of antifungal activity according to time-kill curve. HPLC and qRT-PCR were utilized to evaluate the changes of ergosterol content and expressions of related genes, respectively.</p><p><b>RESULT</b>MICs of EAHD ranged from 156 to 1,250 mg · L(-1), those of FLZ from 256 to above 2,048 mg · L(-1) with FICI approximate 0.066 in combination; SMIC80 of EAHD were higher than 1,250 mg · L(-1), SMIC80 of FLZ were higher than 512 mg · L(-1) and up to above 2,048 mg · L(-1). Combination group also showed synergy effect except one group showing addition effect. The results of T-K experiment also confirmed obviously fungicidal effect when treated for 12 h. When compared with control groups, the ergosterol was reduced 85% and 50% in the treatments of combination and EAHD alone by HPLC, respective- ly. The expressions of ERG1, ERG2, ERG6, ERG7 and ERG11 were upregulated, and ACS1, ACS2, MET6 were downregulated when exposed to FLZ. The expressions of the above genes were downregulated by treatment of EAHD. The expressions of ERG2, ERG6, ERG11 were upregulated, while ERG1, ERG7, ACS1, ACS2, MET6 were downregulated in combination group.</p><p><b>CONCLUSION</b>The combination of EAHD and FLZ exhibited synergy against FLZ-resistant C. albicans through decreasing the synthesis of ergosterol, and resulting in the breakage of cell membrane.</p>
Sujets)
Antifongiques , Pharmacologie , Candida albicans , Métabolisme , Résistance des champignons aux médicaments , Synergie des médicaments , Médicaments issus de plantes chinoises , Pharmacologie , Ergostérol , Fluconazole , Pharmacologie , Tests de sensibilité microbienneRésumé
<p><b>OBJECTIVE</b>To investigate the effects of butyl alcohol extract of baitouweng decoction (BAEB) on the fungal cell surface hydrophobicity (CSH), filamentation and biofilm formation of Candida tropicalis.</p><p><b>METHOD</b>Gradual dilution method was used to determine the MIC. XTT assay was applied to determine the SMIC80. Time-Kill assay was employed to draw the Time-Kill curve. The water-hydrocarbon two-phase assay was used to measure the cell surface hydrophobicity. Scanning electron microscopy (SEM) was applied to observe the morphological changes of the biofilm. Confocal laser scanning microscopy (CLSM) was applied to determine the thickness of the biofilm. The quantification real-time PCR (qRT-PCR) was used to detect expression changes of releated genes (UME6, ALST3 and NRG1). result: The MICs of BAEB against C. tropicalis strains are determined as 64-128 mg x L(-1). The SMIC80 s of BAEB against the biofilm of Candida tropicalis strains are determined as 256-512 mg x L(-1). Time-Kill curve results indicate that BAEB has a promise fungicidal effect at 256 and 512 mg x L(-1). SEM results shows that 512 mg x L(-1) BAEB can inhibit the formation of C. tropicalis biofilm on Silicone catheter, and the morphology of biofilm is also affected by BAEB. The thickness of C. tropicalis biofilm is reduced by BAEB according to CLSM results. Furthermore, qRT-PCR results indicate that expression of UME6 and ALST3 are significantly down-regulated by BAEB 256,512 mg x L(-1), and NRG1 is not affected by BAEB.</p><p><b>CONCLUSION</b>BAEB inhibits effectively the CSH, filamentation and biofilm formation of VVC strains of C. tropicalis.</p>
Sujets)
Humains , Antifongiques , Chimie , Pharmacologie , Biofilms , Candida tropicalis , Génétique , Physiologie , Candidose , Microbiologie , Médicaments issus de plantes chinoises , Chimie , Pharmacologie , Protéines fongiques , Génétique , Métabolisme , Régulation de l'expression des gènes fongiques , Facteurs de virulence , Génétique , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effect of andrographolide (AG) on quroum sensing (QS) and relevant virulence genes of Candida albicans.</p><p><b>METHOD</b>Gas-chromatography-mass spectrometry (GC-MS) was applied to detect the changes in the content of farnesol and tyrosol in C. albicans intervened by AG. The real-time quantitative PCR (qRT-PCR) was adopted to inspect the expressions of relevant virulence genes such as CHK1, PBS2 and HOG1 regulated by QS.</p><p><b>RESULT</b>At 2 h after the growth of C. albican, the farnesol and tyrosol secretions reduced, without notable change after intervention with AG. The secretions were highest at 12 h and decreased at 24 h. After the intervention with different concentrations of AG, the farnesol content reduces, whereas tyrosol increased, indicating a dose-dependence, particularly with 1 000 mg x L(-1) AG. qRT-PCR revealed that 1 000 mg x L(-1) AG could down-regulate CHK1 by 2.375, 3.330 and 4.043 times and PBS2 by 2.010, 4.210 and 4.760 times, with no significant change in HOG1.</p><p><b>CONCLUSION</b>AG could inhibit the farnesol secretion, promote the tyrosol secretion and down-regulate QS-related virulence genes CHK1 and PBS2 expressions.</p>
Sujets)
Candida albicans , Génétique , Physiologie , Diterpènes , Pharmacologie , Farnésol , Métabolisme , Chromatographie gazeuse-spectrométrie de masse , Gènes fongiques , Alcool phénéthylique , Métabolisme , Détection du quorum , Réaction de polymérisation en chaine en temps réel , Virulence , GénétiqueRésumé
<p><b>OBJECTIVE</b>To investigate the effect of andrographolide derivative Yanhuning (YHN) on Candida albicans biofilms in rats.</p><p><b>METHOD</b>The rat C. albicans biofilms subcutaneous catheter model was established by intraperitoneally injecting YHN (40, 20, 10, 5, 2.5 mg x kg (-1)), with the FLC (80 mg x kg(-1)) positive group as the control group. After 7 d, CFU counting and XTT assay were used to evaluate the effect of YHN on C. albicans biofllms in vivo. Scanning electron microscopy (SEM) was applied to observe the morphological changes in rat biofilms intervened by YHN. The real-time fluorescence quantification PCR was adopted to detect expressions of C. albicans adhesion-related genes, such as ALS1, ALS3, HWP1, EAP1 and MP65.</p><p><b>RESULT</b>The YHN group showed much less CFUs on catheter pieces and lower XTT metabolic activity than the blank group, with dosage dependence. SEM also showed that YHN could obviously decrease C. albicans adhesion on subcutaneous catheters in rats. According to qRT-PCR's results, YHN can down-regulate expressions of ALS1, ALS3, HWP1, EAP1 and MP65.</p><p><b>CONCLUSION</b>YHN could inhibit C. albicans biofilms in rats.</p>
Sujets)
Animaux , Rats , Biofilms , Candida albicans , Biologie cellulaire , Physiologie , Cathéters , Microbiologie , Adhérence cellulaire , Diterpènes , Chimie , Pharmacologie , Relation dose-effet des médicamentsRésumé
Along with the increase in fungal infections, Candida albicans prevention and control become the focus of anti-fungal infection at present. This study aims to discuss the effect monomer andrographolide (AG) on C. albicans biofilm dispersion. In the experiment, micro-well plates and medical catheter pieces were used to establish the C. albicans biofilm model. It was discovered by XTT assay and flat band method that 1 000, 500, 250 mg x L(-1) AG could impact the activity of C. albicans biofilm dispersion cells. The morphological structures of residual biofilms on catheter pieces were observed with scanning electron microscopy, which showed that 1 000, 500, 250 mg x L(-1) AG could induce C. albicans biofilm dispersion in a dose-dependent manner, and the dispersed cells were dominated by the yeast phase. According to the real-time fluorescence quantification PCR (qRT-PCR) test, AG could up-regulate HSP90 expression and down-regulate UME6 and PES1 expressions. This study demonstrates that AG could induce C. albicans biofilm dispersion to some extent.
Sujets)
Anti-inflammatoires , Pharmacologie , Biofilms , Candida albicans , Génétique , Physiologie , Diterpènes , Pharmacologie , Relation dose-effet des médicaments , Protéines fongiques , Génétique , Régulation de l'expression des gènes fongiques , Protéines du choc thermique HSP90 , Génétique , Microscopie électronique à balayage , RT-PCR , Facteurs tempsRésumé
<p><b>OBJECTIVE</b>To observe the inhibitory effect of different extract fractions from Longdan Xiegan decoction on biofilms of Candida albicans, and discuss its possible mechanism.</p><p><b>METHOD</b>The micro-dilution method and the XTT reduction assay were adopted to explore the antifungal activity of different extract fractions from Longdan Xiegan decoction and detect the inhibitory effect of different extracts on biofilms of C. albicans. The expression quantity of the adhesion related gene ALS1 and hypha formation SUN41 were detected by qRT-PCR.</p><p><b>RESULT</b>The MICs of extracts from Longdan Xiegan decoction, including petroleum ether, water, butanol, methanol and ethyl acetate, against C. albicans were > 1 000, > 1 000, > 1 000, 125, 125 mg x L(-1). The SMIC50 against biofilms of C. albicanswere > 1 000, > 1000, > 1 000, 500, 500 mg x L(-1). The SMIC50 were > 1 000, > 1 000, > 1 000, > 1 000 and 1 000 mg x L(-1). 1 000 mg x L(-1) ethyl acetate extracts could considerably inhibit the expression of the adhesion related gene ALS1 and hypha formation SUN41.</p><p><b>CONCLUSION</b>The ethyl acetate extract showed the greatest activity against Candida albicans biofilms.</p>
Sujets)
Humains , Antifongiques , Pharmacologie , Biofilms , Candida albicans , Candidose , Traitement médicamenteux , Microbiologie , Médicaments issus de plantes chinoises , Pharmacologie , Hyphae , Tests de sensibilité microbienneRésumé
<p><b>BACKGROUND</b>Older patients with malignant spinal tumors are difficult to treat because they have many co-morbidities including osteoporosis. The purpose of this research is to discuss the technique and clinical outcome of bone cement enhanced pedicle screw fixation combined with vertebroplasty (the Sandwich Procedure) for elderly patients with severe osteoporosis and malignant spinal tumors.</p><p><b>METHODS</b>This study includes 28 consecutive elderly patients with malignant thoracic or lumbar spinal tumors. There were nine patients with myelomas, and 19 patients with metastatic bone tumors. The Sandwich Procedure began with curettage of the tumor and a vertebroplasty with bone cement (polymethyl methacrylate, PMMA), followed by PMMA enhanced pedicle screw fixation. Patients were evaluated with the visual analogue scale (VAS), oswestry disability index (ODI), American Spinal Cord Injury Association (ASIA) neurological function classification, and the radiographic degree of kyphosis (Cobb angle). Data were analyzed using paired t-test to compare the pre- and post-operative values. The complications, local recurrences, and the survival status were also recorded.</p><p><b>RESULTS</b>There was no operative mortality, and the mean operative time was 210 minutes (range 150 - 250 minutes). The average blood loss was 1550 ml (range 650 - 3300 ml). The average amount of cement for vertebroplasty was 3.6 ml (range 3 -5 ml). The VAS, ODI, and ASIA scores were significantly improved after surgery (P < 0.05). However, we found no differences between the pre and post-operative Cobb angles. The shortest survival time was 3 months, and we found no evidence of local recurrence in this group of patients.</p><p><b>CONCLUSION</b>The Sandwich Procedure is a safe operation and provides symptomatic relief in these difficult patients, permitting further treatment with chemotherapy or radiotherapy.</p>
Sujets)
Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Ciments osseux , Vis orthopédiques , Vertèbres lombales , Chirurgie générale , Tumeurs du rachis , Chirurgie générale , Vertèbres thoraciques , Chirurgie générale , Vertébroplastie , MéthodesRésumé
<p><b>BACKGROUND</b>Neuregulin-1 (NRG-1), the ligand of the myocardial ErbB receptor, is a protein mediator with regulatory actions in the heart. This study investigated whether NRG-1 preconditioning has protective effects on myocardial ischemia/reperfusion (I/R) injury and its potential mechanism.</p><p><b>METHODS</b>We worked with an in vivo rat model with induced myocardial ischemia (45 minutes) followed by reperfusion (3 hours). NRG-1 message was detected in the heart using RT-PCR and the protein levels of NRG-1 and ErbB4 were detected by Western blotting analysis. Infarct size was assessed using the staining agent triphenyltetrazolium chloride and cardiac function was continuously monitored. The levels of creatine kinase and lactate dehydrogenase in plasma were analyzed to assess the degree of cardiac injury. The extent of cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and by Western blotting analysis of cleaved caspase-3. We examined the phosphorylation of Akt in the myocardium and the effect of PI3K/Akt inhibition on NRG-1-induced cardioprotection.</p><p><b>RESULTS</b>Transcription and expression of NRG-1 and phosphorylation of its ErbB4 receptor were significantly upregulated in the I/R hearts. NRG-1 pretreatment reduced the infarct size following cardiac I/R in a concentration-dependent manner with an optimal concentration of 4 µg/kg in vivo. NRG-1 pretreatment with 4 µg/kg, i.v. markedly reduced the plasma creatine kinase and lactate dehydrogenase levels. Pretreatment with NRG-1 also significantly reduced the percentage of TUNEL positive myocytes and the level of cleaved caspase-3 in the I/R hearts. Pretreatment with NRG-1 significantly increased phosphorylation of Akt following I/R. Furthermore, the cardioprotective effect limiting the infarct size that was induced by NRG-1 was abolished by co-administration of the PI3K inhibitor LY294002.</p><p><b>CONCLUSIONS</b>The concentration of NRG-1, a new autacoid, was rapidly upregulated after myocardial I/R. NRG-1 preconditioning has cardioprotective effects against I/R injury through a PI3K/Akt-dependent mechanism in vivo.</p>
Sujets)
Animaux , Mâle , Rats , Apoptose , Caspase-3 , Métabolisme , Relation dose-effet des médicaments , Préconditionnement ischémique myocardique , L-Lactate dehydrogenase , Sang , Lésion de reperfusion myocardique , Neuréguline-1 , Pharmacologie , Phosphatidylinositol 3-kinases , Physiologie , Phosphorylation , Protéines proto-oncogènes c-akt , Physiologie , Rat Sprague-Dawley , Récepteurs ErbB , Récepteur ErbB-4Résumé
<p><b>BACKGROUND</b>Controversies on the safety of the cement application between cemented and uncemented total hip arthroplasty (THA) have been existing for decades. The purpose of this study was to observe the changes in mean arterial pressure (MAP), heart rate (HR) and oxygen pressure (PaO(2)) during cemented THA, and to evaluate the intraoperative safety of using the third-generation cementing technique and investigate whether the intraoperative risk is higher in acute femoral neck fracture patients than non-traumatic patients.</p><p><b>METHODS</b>Forty-two patients who underwent cemented THA between November 2005 and September 2007 were prospectively included in this study. The third-generation cementing technique as vacuum mixing and pulsatile lavage was used strictly. The MAP and HR were monitored and documented during each operation. Blood gas analysis was performed at exposure, cup implantation, stem implantation and wound closure. MAP, HR and PaO(2) were compared between pre- and post-cement application. Comparisons of MAP, HR and PaO(2) between patients with acute femoral neck fracture and non-traumatic patients were performed as well.</p><p><b>RESULTS</b>No intraoperative cardiopulmonary complication occurred in these cases. No obvious changes were observed in MAP, HR and PaO(2) after cement application. There was no significant difference in MAP, HR and PaO(2) between acute femoral fracture patients (18 patients) and non-traumatic patients (24 patients).</p><p><b>CONCLUSIONS</b>The results of this study suggested that the invasive blood pressure monitoring and blood gas analysis are essential for patients undergoing cemented THA, especially for patients with femoral neck fracture. The third-generation cementing technique is safe to use in THA.</p>
Sujets)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Arthroplastie prothétique de hanche , Méthodes , Cimentation , Méthodes , Surveillance peropératoire , Méthodes , Études prospectivesRésumé
To explore the effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) preconditioning and postconditioning on myocardial ischemia/reperfusion (IR) injury in rats, the IR injury model was built by stopping perfusion for 40 min followed by reperfusion for 30 min, and the changes of mitochondrial functions, myocardial metabolism and function were measured. Langendorff-perfused isolated rat hearts were divided into 4 groups: control group, persistently perfused with Krebs-Henseleit (K-H) fluid for 100 min; IR group, stopped perfusion for 40 min followed by reperfusion for 30 min; Pre-EET group, preconditioned with 6.24×10(-9) mol/L 11,12-EET for 5 min twice before subjected to ischemia; Post-EET group, postconditioned with 6.24×10(-9) mol/L 11,12-EET for 30 s twice before reperfusion. The computer-based electrophysiological recording system was used to measure the changes of maximal rate of the pressure increase in contract phase (+dp/dt(max)), maximal rate of the pressure decrease in diastole phase of heart (-dp/dt(max)), left ventricular end-diastolic pressure (LVEDP) and difference of left ventricular pressure (DLVP). The activities of lactate dehydrogenase (LDH) in effluent, Ca(2+)-ATPase, Na(+)-K(+)-ATPase and succinate dehydrogenase (SDH) in mitochondria were measured with colorimetry method; superoxide dismutase (SOD) activity was measured with hydroxylamine method and malondialdehyde (MDA) content in myocardial tissues was measured with TBA method. The results showed that: (1) Compared with that in the control group, the myocardial functions, the values of SOD, SDH and Na(+)-K(+)-ATPase were decreased in IR group (P<0.05); the values of LDH, MDA and Ca(2+)-ATPase were increased (P<0.05) in IR group. (2) Compared with that in IR group, the values of SDH and Na(+)-K(+)-ATPase were increased (P<0.05) and the value of Ca(2+)-ATPase was decreased (P<0.05) in both Pre-EET and Post-EET groups. But no significant differences were detected between Pre-EET and Post-EET groups. (3) Compared with IR treatment, both 11,12-EET preconditioning and postconditioning caused significant decreases in MDA content and leakage of LDH, amendment of heart functions and increases in SOD activity (P<0.05). But there were no significant differences between 11,12-EET preconditioning and postconditioning. These results indicate that 11,12-EET preconditioning and postconditioning can protect myocardium from IR injury by improving mitochondrial functions, up-regulating the activities of Na(+)-K(+)-ATPase and SDH, and down-regulating the activity of Ca(2+)-ATPase in mitochondria. Moreover, 11,12-EET preconditioning and postconditioning also elevate the activity of SOD and reduce the content of MDA, suggesting that 11,12-EET can depress the oxidative stress in IR rat heart.
Sujets)
Animaux , Rats , Acide éicosatriénoïque-8,11,14 , Pharmacologie , Calcium-Transporting ATPases , Métabolisme , Coeur , Postconditionnement ischémique , Préconditionnement ischémique , L-Lactate dehydrogenase , Métabolisme , Lésion de reperfusion myocardique , Traitement médicamenteux , Stress oxydatif , Sodium-Potassium-Exchanging ATPase , Métabolisme , Succinate Dehydrogenase , Métabolisme , Superoxide dismutase , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effects of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) preconditioning and postconditioning on Ca(2+)-handling proteins in myocardial ischemia/reperfusion (IR) injury in rats and reveal the effects and mechanism of 11, 12-EET on cardioprotection. METHODS The IR injury model was built by stopping perfusion for 40 minutes followed by reperfusion for 30 minutes. The isolated Langendorff-perfused rat hearts were divided into 4 groups: control group, IR group, EET preconditioning (Pre-EET) group and EET postconditioning (Post-EET) group. The computer-based electrophysiological recorder system was used to measure the changes of the maximal rate of pressure increased in the contraction phase (+dp/dt(max)), the maximal rate of pressure decreased in the diastole phase (-dp/dt(max)), the left ventricular end diastolic pressure (LVEDP) and the difference of left ventricular pressure (delta LVP). The activity of Ca(2+)-ATPase in sarcoplasmic reticulum was measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of C(a2+)-handling protein [sarcoplasic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), ryanodine receptor type 2 (RyR,), and 1, 4, 5-trisphosphate inositol receptor type 2 (IP3 R2) ] mRNAs level.</p><p><b>RESULTS</b>Compared with IR group, the myocardial functions, the value of Ca(2+)-ATPase, and the expressions of IP3 R2 mRNA were significantly increased and the expression of PLB mRNA was significantly decreased in both Pre-EET group and Post-EET group (P < 0.05, P < 0.01). And the expression of SERCA mRNA was significantly increased in Pre-EET group (P < 0. 05). However, no significant differences were detected between Pre-EET and Post-EET groups. Moreover, the expression of RyR2 mRNA was not significantly different among all groups.</p><p><b>CONCLUSIONS</b>11, 12-EET preconditioning and post-conditioning can protect myocardium from IR injury by elevating the activity of Ca(2+)-ATPase in sarcoplasmic reticulum, up-regulating the expression of IP3 R2 mRNA, and down-regulating the expression of PLB mRNA. Moreover, up-regulating the expression of SERCA mRNA maybe one of mechanisms of 11, 12-EET preconditioning on cardio protection against IR injury.</p>
Sujets)
Animaux , Rats , Acide éicosatriénoïque-8,11,14 , Pharmacologie , Protéines de liaison au calcium , Métabolisme , Récepteurs à l'inositol 1,4,5-triphosphate , Métabolisme , Préconditionnement ischémique myocardique , Méthodes , Lésion de reperfusion myocardique , Métabolisme , Canal de libération du calcium du récepteur à la ryanodine , Métabolisme , Sarcoplasmic Reticulum Calcium-Transporting ATPases , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effects of 11, 12-epoxyeicosatrienoic acids (11, 12-EET) on the degree of hypoxia/reoxygenation injury in human umbilical vein endothelial cells ( HUVECs), and reveal the possible pathway of EET on protection.</p><p><b>METHODS</b>Primary cultured HUVECs were randomly divided into control group, hypoxia/reoxygenation group, 11, 12-EET control group, 11, 12- EET hypoxia/reoxygenation group, inhibition of extracellular signal-regulated kinase (ERKI/2) group, and inhibition of nitric oxide synthase (NOS) group. Hypoxia/reoxygenation injury model in HUVECs was established by exposure to hypoxia (2% O2, 5% CO2 and 93% N2) for 3 hours, followed by reoxygenation (95% air and 5% CO2) for 1 hour. The evaluation of the endothelial cells were made by immunohistochemistry. The cell viability was monitored by MTT assay. Colorimetry method was used to assay the lactate dehydrogenase (LDH) , malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in culture medium. Western blot was used to detect the expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated ERK1/2 in HUVECs.</p><p><b>RESULTS</b>11, 12-EET caused minor injury in normal oxygen incubated HUVECs; however, in hypoxia/reoxygenation HUVECs, it raised the cell viability markedly, decreased the LDH release and MDA content, and increased the activity of SOD and the expressions of eNOS and phosphorylated ERK1/2.</p><p><b>CONCLUSIONS</b>11, 12-EET may prevent against endothelial cell hypoxia/reoxygenation injury. The mechanism may be related to the increased activity of SOD, elimination of oxygen-derived free radicals, and reduction of eNOS and phosphorylated ERK1/2 lesion caused by hypoxia/reoxygenation.</p>
Sujets)
Humains , Acide éicosatriénoïque-8,11,14 , Pharmacologie , Hypoxie cellulaire , Physiologie , Survie cellulaire , Cellules cultivées , Cellules endothéliales , L-Lactate dehydrogenase , Métabolisme , Malonaldéhyde , Métabolisme , Mitogen-Activated Protein Kinase 3 , Nitric oxide synthase type III , Lésion d'ischémie-reperfusion , Superoxide dismutase , Métabolisme , Veines ombilicales , Biologie cellulaireRésumé
<p><b>OBJECTIVE</b>To determine whether Betahistine mesilate is effective in treating tinnitus.</p><p><b>METHODS</b>Randomized, prospective, double-blind, controlled trial was used in our study. The study group consisted of 60 adult patients who consulted our outpatient clinic complaining of subjective tinnitus, excluded objective tinnitus and the patients who had tinnitus caused by obvious diseases, such as outer and middle ear diseases. Thirty patients were given Betahistine mesilate and Flunarizine Hydrochloride as an experimental group, 30 patients were given Vitamin B6 and Flunarizine Hydrochloride as a control group. After a week of treatment the efficacy of the medicines in two groups was observed. Tinnitus questionnaire was performed before the treatment, and pure tone audiogram, tinnitus pitch and loudness matching were performed both in the beginning and at the end of the treatment.</p><p><b>RESULTS</b>Completion of treatment, tinnitus loudness matching assessment showed that the efficacy of the Betahistine mesilate group was better then the control group. The efficacy of treatment was respectively 65.5% by per protocol (PP) and 63.3% by intend to treat (ITT) in the Betahistine mesilate group and 39.3% by PP and 36.7% by ITT in the control group. The difference of tinnitus loudness improvement rate between the experimental group and control group was statistically significant. But the subjective tinnitus improvement rate showed no difference between two groups. There were not serious side effects in the two groups.</p><p><b>CONCLUSIONS</b>Betahistine mesilate can be a choice for tinnitus treatment clinically. Further studies of larger series and placebo-controlled trial are needed.</p>
Sujets)
Adolescent , Adulte , Sujet âgé , Humains , Adulte d'âge moyen , Jeune adulte , Bétahistine , Utilisations thérapeutiques , Méthode en double aveugle , Association de médicaments , Flunarizine , Utilisations thérapeutiques , Études prospectives , Acouphène , Traitement médicamenteux , Résultat thérapeutiqueRésumé
<p><b>OBJECTIVE</b>To explore the relationship between sample size and variance of means for personal noise exposure in weaving workers as to contributing evidence for establishing personal noise exposure measurement guideline.</p><p><b>METHODS</b>A personal noise exposure measurement database from a group of weaving workers was used in the randomized re-sampling data analysis. The sampling cases were one number selecting from one to fifteen at each randomized re-sampling procedure. The randomized re-sampling was one thousand times from original personal noise exposure measurement database to get one thousands of re-sampling database. One thousands of L(Aeq.8 h) mean were calculated by re-sampling databases. The variation of randomized re-sampling means was analyzed for different re-sampling numbers.</p><p><b>RESULTS</b>The change for narrow trend of maximum, minimum, 95 percent number, 5 percent number of L(Aeq.8 h) mean was faster when randomized re-sampling number was smaller in variation vs randomized re-sampling number curve analysis. After that, the change for narrow trend of L(Aeq.8 h) mean was smooth for increasing the randomized re-sampling numbers. The 95% - 5% of L(Aeq.8 h) mean was about half for randomized re-sampling four cases (3.30 dB) vs one case (7.40 dB), and about one third for seven cases (2.44 dB), and about one fourth for eleven cases (1.85 dB).</p><p><b>CONCLUSION</b>The sample size in personal noise exposure measurement guideline could be selected from four to eleven.</p>