Objective To investigate the influence of panton-valentine leucocidin (PVL) on expression of Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signals and IL-8,IL-6 in THP-1 macrophages,and to study the mechanism of PVL-related lung tissue damage.Methods THP-1 cells were cultured in the presence of 100 nmol/L phorbol-12-myristate 3-acetate (PMA) for 48 h to induce monocytemacrophage differentiation.rPVL-F and rPVL-S were induced and expressed from the recombinant plasmid,respectively purified with chromatographic column. After that,THP-1 macrophages were incubated with rPVL,and then ELISA was performed to test expression of IL-8 and L-6 in supernatants fluid; RT-PCR was performed to detect expression of IL-8,L-6 and TLR4 ; NF-κB was analyzed by Western blot and immunohistochemistry method.Results PVL was able to induce expression of IL-8 and IL-6 in THP-1 macrophages in time-and concentration-dependent manners.PVL could also significantly promote the activation of TLR4/NF-κB signals.Conclusion PVL can activate the expression of TLR4/NF-κB signals,and increased the high expression of inflammatory cytokines.Maybe it's the mechanism of action of PVL exerts the function of lung tissue damage.

Objective To investigate effect of PDTC on the NF-κB activation and the expression of inflammatory cytokines in THP-1 macrophages induced by rPVL.Methods The study was divided into three groups:PBS-treated control group,rPVL-treated group and PDTC group which was given 100 μmol/L PDTC at 60 min before rPVL exposure.Immunohistochemistry method was used to test the translocation of NF-κB protein; the expression of NF-κB and IκB protein was analyzed by Western blot; RT-PCR and ELISA was performed to test expression of IL-8 and L-6 in THP-1 macrophages.Results Compared with rPVL-treated group,the activation of NF-κB and the expression of IL-8 and L-6 in PDTC group was significantly decreased.The protein secretions of IL-8 and IL-6 were reduced to 6.78 ng/ml,3.88 ng/ml,receptively(P ＜0.05).Conclusion The inhibitor of NF-κB,PDTC,could significantly decrease the secretion of pro-inflammatory in THP-1 macrophages by rPVL,and it suggested that PDTC played an important role in protecting tissues from damage induced by rPVL.

Objective To investigate the influence of tethered cord syndrome (TCS) on the up-per urinary tract and its etiology. Methods Forty patients with TCS diagnosed by spinal MRI were enrolled in this study. There were 21 males and 19 females with mean age of 23 years old. The course of disease ranged from 1 to 40 years. Urinalysis, mid-stream urine culture, serum creatinine(SCr), urinary system ultrasound, IVU, eystography and urodynamic study were carried out on all patients. Results Urinary tract infection was found in 17 patients and increased level of SCr was found in 6 pa-tients (251.64±98.5μmol/L). Of the 29 patients who underwent urinary system ultrasound examina-tion, 12 cases had hydronephroais and dilated upper ureter. Of the 30 patients who underwent IVU, 10(33.3%) had ureterectasia and hydronephrosis, 22 cases had bladder turriform or Christmas tree like deformity with diverticulum and trabeculum. Of the 22 patients accepted cystography, 17 cases had vesieoureteral reflux on 27 sides. Post-void residual (PVR) was evaluated in 35 patients and found increased in 31 cases. Cystometry had been done in 33 patients. The mean value of maximal detrusor pressure (Pdetmax) during filling phase was 41.2±20.9 cm H2O. The detrusor compliance was 22.35±18.8 ml/cm H2O. During voiding phase, detrusor-sphincter dyssynergia(DSD)was observed in 16 patients, detrusor areflexia was observed in 16 patients and detrusor underactivity was observed in 13 patients. Resting urethral pressure profilemetry was measured in 16 patients. Maximal urethral closure pressure (MUCP) was 76.1±33.1 cm H2O. The upper urinary tract deterioration was de-fined as increased SCr, hydronephrosis or vesicoureteral reflux. There were 20 patients diagnosed as upper urinary tract deterioration. The compliance of the upper urinary tract deteriorating group and the no-deteriorating group was 9.4±7.8 vs 19.3±15.8 ml/cm H2O, Pdetmax was 43.1±21.2 vs 24.0±11.9 cm H2O, PVR 189.0±138.0 vs 47.8±36.8 ml, MUCP 86.2±32.4 vs 46.8 5±20.8 cm H2O, incidence of damaged detrusor 100.0% vs 69.2% and DSD 65.0% vs 23.1%, respectively. There were significant differences between the 2 groups(P<0.05). And when comparing the VUR group with no VUR group, the incidence of urinary tract infection was 94.1%(16/17) vs 20.0%(1/ 5) (P=0.003). And when comparing urinary tract infection group with no infection group, the inci-dence of upper urinary tract deterioration was 88.2% (15/17) vs 21.7%(5/23)(P=0.000). Condn-sion Low compliance bladder, high Pdetmax during filling phase, increased PVR, high MUCP, damage of detrusor contractive function and DSD are the risk factors for upper urinary tract deteriora-tion in the TCS patients.

Objective To investigate the effects of multimodal analgesia of parecoxib and fentanyl on perioperative immune functions in patients of hepatocellular carcinoma (HCC).Methods Eighty HCC patients scheduled for hepatectomy were randomly divided into two groups:parecoxib sodium combined with fentanyl group (group P,40 cases) and fentanyl group (group C,40 cases).The percentages of CD3 +,CD4+,CD8+,CD4+/CD8+ T cells,CD3-CD16+ CD56+ (NK),interleukin-4 (IL-4),interferon-γ (IFN-γ) and the ratio of IFN-γ/IL-4 were detected at the following time points:30 minutes before induction of anesthesia (T0),at the end of the surgery (T1),24 h after surgery (T2) and 72 h after surgery (T3).The analgesic effects were estimated by visual analogue scale (VAS) after surgery.Total fentanyl consumption and adverse effects were also recorded.Results The percentages of CD3 + T cells were significantly lower in group C than that in group P at T2 (t =2.155,P ＜0.05).The percentages of NK in group P were recovered nearly to baseline (T0) at T2,which was higher than that of group C (t =2.791,P ＜0.05).In group C,the percentages of CD3 + T cells and NK has not recovered to baseline at T3 (respectively t =3.065,3.231,P ＜ 0.05).In group P,IL-4 serum levels were significantly lower than those in group C,while IFN-γ serum levels were significantly higher than those in group C at T2 (respectively t =2.173,2.100,P ＜0.05).From T2 to T3,the ratio of IFN-γ/IL-4 significantly increased in group P than those in group C (respectively t =3.259,2.203,P ＜ 0.05).VAS scores at rest and on cough in group P were significantly lower than those in group C at 2 h,6 h,12 h and 24 h after operation (respectively t =8.661,9.726,9.147,7.109,P＜0.05;t =8.569,9.614,9.144,8.509,P＜0.05).The total fentanyl consumption in group P was lower than that in group C (t =2.636,P ＜ 0.05).There were no significant differences regarding the incidence of adverse effects between the two groups.Conclusions Perioperative multimodal analgesia of parecoxib sodium combined with fentanyl enhances the analgesic efficacy,and reduces the dosage of opioid consumption,helps recover the cell immunity function of HCC patients after hepatectomy.

Objective To measure the level of androgen receptor (AR) mRNA in peripheral blood monocytes (PBMCs) and serum testosterone level of patients with gouty arthritis (GA) and healthy controls (HC),and to explore the role of testosterone and AR in the pathogenesis of GA.Methods Chemilluminescence was used to detect the level of serum testosterone in GA [including 119 acute GA (AGA) and 60 nonacute GA (NAGA) patients] and 47 HC group.Real-time quantitative polymerase chain reaction (RT-qPCR)was used to measure AR mRNA in PBMCs from 41 GA and 35 HC.Western blotting was used to measure PBMCs AR in GA and HC for each 6 cases.One-way ANOVA,t test and Spearman's correlation were adopted for statistical analysis.Results Serum testosterone was significantly reduced in AGA and NAGA group compared to that in HC group [(6.1±1.5) ng/ml,P＜0.01,respectively],and the expression was lower in the AGA [(3.7±1.4) ng/ml] group [(4.9±2.0) ng/ml] than that in the NAGA group (P＜0.01).The level of AR mRNA and protein was much lower in the GA group than that in the HC group (P＜0.01,respectively).Negative correlations was detected between AR mRNA and uric acid in GA patients.There was negative correlation between serum testosterone and VLDL,GLU; meanwhile,positive correlation was found between serum testosterone and HDL (P＜0.05,respectively) in NAGA patients.There were no correlations between testosterone and other laboratory data.There was no correlation between AR and other laboratory data in GA patients and healthy controls (P＞0.05,respectively).Conclusion Altered expression of testosterone and its receptor may be involved in the pathogenesis of gouty inflammation.Further study will be needed to shed light on the exact role of androgen and AR in gout.

Objective: To observe the impact of cardiac resynchronization therapy (CRT) on ventricular remodeling in patients with III°atrio-ventricular block (AVB) combining systolic dysfunction.
Methods: A total of 49 III °AVB patients received CRT in our hospital from 2009-01 to 2014-10 were studied. Echocardiography was conducted at pre-operation and 6, 12 months post-operation to measure left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and mitral regurgitation (MR) grade in order to observe the changes of cardiac structure and function in relevant patients.
Results: Compared with pre-operative condition, at 6 months post-operation, LVEF was increased (4.92±5.24)%and at 12 months post-operation, it was further increased (5.02±6.52)%, both P<0.05;at 6 months post-operation, LVESV reduced (25.02±17.95) ml and at 12 months post-operation, it was further reduced (24.79±22.49) ml, both P<0.05. Compared with pre-operative condition, at 6 months post-operation, LVEDV dropped (25.61±24.24) ml, LVEDD dropped (3.22±2.91) mm, LVESD dropped (4.43±2.86) mm and MR grade dropped 0.49±0.76, all P<0.05. Compared with 6 months post-operation, at 12 months post-operation, LVEDV declined (28.18±22.36) ml, LVEDD declined (4.17±3.14) mm, both P<0.05, LVESD declined (4.92±4.40) mm, P<0.01 and MR grade declined (0.22±0.55), P<0.05.
Conclusion:CRT may reverse ventricular remodeling and improve cardiac function in patients with III°AVB combining systolic dysfunction.

Objective: To analyze the predictors of left ventricular reverse remodeling in patients with III? atrio-ventricular block (AVB) combining left ventricular systolic dysfunction after cardiac re-synchronization therapy (CRT). Methods: A total of 65 III? AVB patients received CRT in our hospital from 2009-01 to 2015-05 were enrolled. Clinical information before and after the operation were recorded. Left ventricular reverse remodeling was deifned by left ventricular end systolic volume (LVESV) decreased 15% or left ventricular ejection fraction (LVEF) increased≥5% at 12 months after CRT. The patients were divided into 2 groups: Reversal group,n=36 and No reversal group,n=29. Clinical condition was compared between 2 groups, predictors for CRT reversing left ventricular remodeling were evaluated by two classiifcation Logistic regression analysis. Results: The patients' average age was (62±14) years and 36/65 (55.4%) with reverse remodeling. In Reversal group, the ratios of female (P=0.011), baseline QRS width>120ms (P=0.001), inter-ventricular mechanical delay (IVMD)≥40 ms (P=0.027) and standard deviation of time-to-minimum systolic volume of 16 segments [Tmsv16-SD (%R-R)≥8.3%, (P=0.001)] were higher than those in No reversal group. Two classiifcation Logisitic regression analysis indicated that female (OR=6.228, 95%CI 1.561-24.842, P=0.01), QRS duration>120 ms (OR=7.778, 95% CI 1.996-30.769,P=0.003) and Tmsv16-SD (%R-R)≥8.3% (OR=8.134, 95% CI 2.064-32.057,P=0.003) were the independent predictors for ventricular reverse remodeling . Conclusion: Female, QRS>120ms and Tmsv16-SD (%R-R)≥8.3% could be used as the predictors for CRT reversing left ventricular remodeling in III? AVB patients combining left ventricular systolic dysfunction.

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cadherins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cytokines ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Vimentin/metabolism

Objective: To investigate the efficacy and safety of the recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein (rhTNFR: Fc, etanercept) for the treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) . Methods: In September 2011 to February 2016, 12 patients with OMLDT were treated with etanercept 25 mg, subcutaneous injection, twice per week, doubling of first dose. The course of treatment was 6 weeks. The drug eruption area and severity index (DASI) score, the proportion of patients achieving a 50%, 75% and 90% reduction in DASI (DASI50, DASI75, DASI90) and the serum level of TNF-α were used to assess the efficacy at different times. Adverse reactions were also recorded and evaluated. The results were statistically analyzed by nonparametric Friedman test and repetitive measurement ANOVA using the software SPSS19.0. Results: After 4 weeks treatment, the DASI score decreased form 56.33±7.02 to 0.50±0.91 (P<0.01) . The DASI50, DASI75 and DASI90 were all increased to 12 (100%) . The serum level of TNF-α decreased form (43.74±41.62) pg/ml to (3.03±0.47) pg/ml (P<0.01) . Statistically significant difference was observed from the above indexes. There were no adverse reactions in clinical application. Conclusion Recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein may be a safe and effective drug in the treatment of OMLDT.