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Purpose@#Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. @*Methods@#TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. @*Results@#TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. @*Conclusions@#These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.
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Purpose@#Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. @*Methods@#TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. @*Results@#TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. @*Conclusions@#These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.
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Objective To investigate the safety and efficacy of holmium laser transurethral enucleation of the prostate (HoLEP) for large volume of prostatic hyperplasia (BPH) with navigation of ultrasonic anatomical landmarks.Methods Data of 242 patients with BPH (≥ 80 cm3) underwent domestic HoLEP from Jan.2016 to Jan.2018 were retrospectively analyzed.General data,IPSS,QOL,prostate volume,PSA were assessed.Their average volume of prostate was (103.2 ± 21.4) cm3,the average PSA was (2.6 ± 1.4) ng/ml,the residual urine volume was (105 ± 75) ml,Qmax was (6.4 ± 5.2) nd/s,IPSS score was 22.5 ± 5.3 and QOL score was 4.8 ± 1.2.Result All patients were completed the operation successfully and their LUTS indicators were greatly improved.The enucleation time was between 25 and 80 min,average (49.0 ± 12.2) min;the mass of wet weight of gland was (70.5 ± 15.3) g;the removal efficiency was (1.6 ±0.3) g/min.The IPSS score dropped to 14.8 ± 6.5,P ＜ 0.01;QOL score dropped to 2.6 ± 1.5,P ＜ 0.01;PSA dropped to (1.1 ± 1.2) ng/ml,P ＜ 0.01;the maximum urinary flow rate growth to (16.5 ±7.1) ml/s,P ＜0.01.Conclusion For large volume of prostatic hyperplasia,holmium laser transurethral enucleation with ultrasonic navigation surgery is safe and efficient.
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Objective To understand the etiology and clinical characteristics of candidemia, and the diagnostic value of(1, 3)-β-Dglucan. Methods This analysis included 31 patients with candidemia, 39 patients with Candida deep colonization, and 50 healthy subjects, who were enrolled from Wuyi Chinese Hospital Affiliated to Jinan University during the period from September 2015 to March 2018. Clinical data such as fungal culture, clinical features, and serum(1, 3)-β-D-glucan level were analyzed and compared between groups. Results Overall, 13 strains of Candida albicans and 18 strains of non-albicans Candida were isolated from the 31 patients with candidemia. The incidence of candidemia was associated with old age(>65 years), prior surgery(≤7 days), indwelling catheter(≥2 catheters and lasting ≥5 days), duration of mechanical ventilation(≥5 days)(P<0.05), but not associated with sex, underlying disease, prior use of anmicrobial and antifungal agents, immunosuppressant or glucocorticoid, or hypoproteinemia(P>0.05). Serum level of(1, 3)-β-D-glucan was significantly higher in candidemia patients than in the patients with candida deep colonization and healthy controls(P<0.05). The sensitivity and specificity of(1, 3)-β-D-glucan in diagnosing candidemia were 87.1％ and 96.0％, respectively. The level of(1, 3)-β-D-glucan was significantly higher in candidemia with bacterial infection than candidemia without bacterial infection(P<0.05). The level of of(1, 3)-β-D-glucan was also significantly higher in the candidemia caused by Candida albicans alone than that caused by non-albicans Candida alone(P<0.05). Conclusions Non-albicans Candida is more prevalent than Candida albicans in candidiasis, but Candida albicans is still the most important Candida species. The incidence of candidemia is asociated with advanced age(>65 years), prior surgery within 7 days, indwelling catheters(≥2 catheters and lasting ≥5 days), and mechanical ventilation(≥5 days). Serum(1, 3)-β-D-glucan level is valuable for early diagnosis of candidemia.
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Objective The objective of this study was to investigate the relationship between CYP2D6 gene polymorphisms and the concentrations of tamoxifen metabolites in breast cancer patients. Methods Peripheral blood samples from breast cancer pa-tients were collected to detect the single nucleotide polymorphism(SNP)of s16947,rs1065852 and rs28371725 gene sites on CYP2D6 gene from January 2010 to December 2012. Genotypes of the three SNPs of CYP2D6 and the concentrations of tamoxifen metabolites were detected in breast cancer patients. Statistical analysis was performed using an independent sample Kruskal-Wallis test in a non-parametric test. Results There was a statistical difference in the concentrations of tamoxifen metabolites 4-OH-N-D-TAM and 4′OH-N -D -TAM in the blood in different CYP2D6 gene genotype carriers at rs16947 site ( P =0. 049), indicating that the rs16947 site of CYP2D6 gene affected the metabolism of tamoxifen drug in breast cancer patients. Conclusion The genotype of CYP2D6 gene at rs16947 site is related to the blood concentration of tamoxifen metabolites in breast cancer patients.
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Objective To explore the relationship between lipids profile and body composition in the young and middle?aged adults. Method The relationship between body composition and lipids profile was examined in 642 adults (21-60 years, 178 male, 464 female). According to the result of body composition assessment, they were assigned to three groups: Normal (N, n=272), Obesity (O, n=245), Sarcopenic Obesity (SO, n=125). The lipids profile among three groups and its related factors were analyzed. Results In groups N, O and SO, the levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein?cholesterol (LDL?C) increased gradually (P<0.01), and the high density lipoprotein?cholesterol (HDL?C) level decreased gradually (P<0.01). In a multiple logistic regression analysis, the odds ratio for high levels of TC, TG, LDL?C and low level of HDL?C risk increased gradually in groups N, O and SO [compared to group N, the odds ratio of the four kinds of dyslipidemia in group O were 2.617 (1.117-6.132), 3.549 (1.481-8.503), 4.618 (1.288-16.564), 1.222 (0.529-2.822), respectively, and in group SO were 5.915 (2.512-13.926), 10.430 (4.400-24.722), 9.522 (2.637-34.388) , 4.253 (1.957-9.242) , respectively]. After adjusting for age, sex, waist?to?hip ratio and visceral fat area, the odds ratio for high level of TG risk still increased gradually in group N, O and SO [compared to group N, the odds ratio of group O was 3.565 (1.319-9.632), and of group SO was 8.173 (2.685-24.881)]. Moreover, the odds ratio for high TC and low HDL?C levels of group SO were higher than those of group N [compared to group N, the odds ratio in group SO were 5.658 (1.871-17.111), 6.823 (2.119-21.969) respectively]. With stepwise multivariate logistic regression analysis, for male, the related factors for high levels of TC, TG and low level of HDL?C were high percentage of body fat;sarcopenia, sarcopenia obesity;sarcopenia, respectively. For female, the related factors for high levels of TC, TG and LDL?C were sarcopenia, aging;high percrntage of body fat, aging;sarcopenia, aging, respectively. Conclusion SO was the main risk factor for dyslipidemia in young and middle?aged adults, even more severe than obesity alone and sarcopenia was the risk factor of high TG, low HDL?C levels for male;and the risk factor of high TC, high LDL?C levels for female.
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<p><b>BACKGROUND</b>Lymphocyte function and homeostasis is associated with immune defence to infection. Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia. The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.</p><p><b>METHODS</b>Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study. Annexin V and propidiumiodide (PI) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry. Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2, cytochrome c (Cyt-C), caspase-9 and caspase-3 were analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P < 0.05). Transmission electron microscopy showed lymphocyte shrinkage and breakage, chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9, caspase-3 and Cyt-C were elevated (P < 0.05) in diabetic patients.</p><p><b>CONCLUSIONS</b>The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population. Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Apoptosis , Physiology , Caspase 3 , Genetics , Caspase 9 , Genetics , Diabetes Mellitus, Type 2 , Metabolism , Lymphocytes , Cell Biology , Metabolism , Microscopy, Electron, Transmission , Mitochondria , Metabolism , Real-Time Polymerase Chain Reaction , bcl-2-Associated X Protein , GeneticsABSTRACT
Objective To evaluate the effect of preoperative oral finasteride on patients with benign prostate hyperplasia (BPH) undergoing holmium lasterenucleation of prostate (HoLEP).Methods A total of 156 BPH patients from Department of Urology in Shanghai Ninth People's Hospital from Sep.2010 to Mar.2012 was analyzed retrospectively.79 patients receiving oral 5 mg/d finasteride before operation were selected as medication group,and the 77 patients without taking finasteride were selected as control group.The perioperative data,including operation time,amount of washing fluid during operation,preoperative and postoperative changes of hemoglobin level and postoperative bladder washing time were compared between two groups.Results Compared with control group,the changes of hemoglobin level after HoLEP,amount of washing fluid during operation,and postoperative bladder washing time with normal saline were significantly decreased in experimental group[(1.08±0.27) g/L vs.(1.55±0.32) g/L,(27.51±3.67) L vs.(36.89±6.47) L,(24.85±4.17) h vs.(35.87±5.10) h,all P＜0.05].Conclusions Oral finasteride before HoLEP can reduce perioperative bleeding and the volume of bladder irrigation with normal saline.
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Objective To evaluate the value of ghrelin on predicting prognosis in patients with chronic heart failure (CHF) after hospital discharge.Methods Totally 145 patients withCHF (age≥60 years,83 males and 62 females) were divided into 3 subgroups by New York Heart Association classification (NYHA):class Ⅱ (n=48),class Ⅲ(n=57) and class Ⅳ(n =40).According to the basic diseases,the CHF group was divided into five subgroups.All patients were followed up for about 2 years.The study included 55 healthy control subjects (30 males and 25 females).Results Plasma ghrelin level was lower in CHF cases (1.66±0.28) μg/L than in control subjects (2.27±0.26) μg/L (t 3.77,P＜0.01).The ghrelin level in NYHA Ⅱ(1.85±0.13) μg/L were higher than in NYHA Ⅲ (1.56±0.28) μg/L,the latter were higher than in NYHA Ⅳ (1.27±0.24) μg/L (P＜0.05).The plasma ghrelin level of patients after treatment (1.98±0.25) μg/L was increased compared with that of before treatment (1.66±0.28) μg/L (P＜0.05).No significant difference was found among the five basic disease groups (P＞0.05).During the follow up periods of (637±97)days,plasma ghrelin level was decreased in patients with cardiovascular event (1.26±0.38) μg/L than in patients without cardiovascular event (1.86±0.34) μg/L.The plasma ghrelin was negatively correlated with left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (P＜0.05).Conclusions The plasma ghrelin in elderly patients with CHF is decreased than in healthy adults,and its level is lower in patients with severe heart failure.The plasma ghrelin is a predictor of cardiovascular event and death in elderly patients with CHF.
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Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.
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Aged , Animals , Humans , Aging , Genetics , Metabolism , Pathology , Amyotrophic Lateral Sclerosis , Genetics , Metabolism , Pathology , Animals, Genetically Modified , Disease Models, Animal , Drosophila melanogaster , Genetics , Metabolism , Gene Expression , Microscopy, Electron, Scanning , Motor Neurons , Metabolism , Pathology , Mushroom Bodies , Metabolism , Pathology , Mutant Proteins , Genetics , Metabolism , Mutation , Photoreceptor Cells, Invertebrate , Metabolism , Pathology , Plasmids , RNA-Binding Protein FUS , Genetics , Metabolism , Recombinant Fusion Proteins , Genetics , Metabolism , Retinal Degeneration , Pathology , TransfectionABSTRACT
Objective To explore the modulation of chlorogenic acid (CGA) on glucose metabolism in HepG2 cells pretreated with high insulin and high oleic acid (OA). Methods Cultured HepG2 cells induced by high insulin and oleic acid for insulin resistance and steatosis respectively, were co-cultured with different concentrations of CGA (10,20,40,80 mg/L) for 24h. The morphological changes were observed and glucose consumptions of cells were measured by glucose oxidase method. Results Compared to control group, CGA could significantly increase glucose consumption of normal HepG2 cells and the dosedependent effect was noted between 10-40 mg/L(P
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Objective To analyze clinical manifestation and identify prognostic factors in patients with acute respiratory distress syndrome (ARDS) caused by cytomegalovirus (CMV) pneumonia after kidney transplantation.Methods Fifty five kidney transplant recipients' data were analyzed in a case-control study of patients with a primary discharge diagnosis of ARDS caused by CMV pneumonia.Results The mortality of ARDS after kidney transplantation was 56.4%;when association with mechanical ventilation,it was 72.5%.In multivariate Logistic regression analysis,numbers of complications (odds ratioOR2.60,95% confidence intervalCI1.00~6.76),severity of diffuse infiltrates in chest X-ray (OR 11.83,CI 1.14~123.07),mechanical ventilation (OR 11.83,CI 1.14~123.07) were independent risk factors to death.Conclusion Even in modern era,kidney transplant recipients with ARDS after kidney transplantation are still at high risk for death.Numbers of complications,severity of diffuse infiltrates in chest X-ray,mechanical ventilation are associated with poor outcomes.
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Objective To investigate the protective effect of losartan on acute ischemia-reperfusion(I/R)(injury) of pancreas in rats.Methods Seventy-two Wister rats were randomly divided into 3 groups:(1)(Control group);(2)Ischemia-reperfusion group:the anterior mesenteric artery and the celiac artery were(occluded) for 15 min,30min and 60min followed by 6 hours reperfusion;(3)Losartan group:losartan(40mg/kg)were administered by gavage at 12h and 1h before arterial occlusion.The pathologic changes of pancreatic tissue were observed under light microscopy;TUNEL was used to detect apoptosic of pancreatic cells;Bcl-2 expression in the pancreatic cells of rats was analyzed by immunohistochemistry technique.(Results) Losartan treatment reversed the histological abnormalities including infiltration of inflammatory cells and atrophy of acinar cells.Compared with losartan group,pancreatic tissue of I/R group exhibited increased MDA[((20.1?1.2))nmol/g and((34.9?2.6)) vs(17.9?2.1)nmol/g and(25.2?3.3)nmol/g,P