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Objective:To predict the inflammatory activity of patients with ankylosing spondylitis (AS) after 12 weeks treatment with recombinant human tumor necrosis factor-α receptor Ⅱ immunoglobulinG Fc fusion protein (rhTNFR:Fc) by Doppler ultrasonography at baseline.Methods:A total of 60 patients with AS were selected, and their general clinical characteristics before and after treatment were compared. Meanwhile, Doppler ultrasonography of the sacroiliac joint was performed to compare the Doppler parameters before and after treatment, and the correlation between baseline Doppler ultrasonography and clinical characteristics was analyzed, along with its diagnostic performance. The pre-treatment and post-treatment parameters were compared to the measured data followed by paired t-test for normal distribution, and the counting data were paired with Chi- square test. Pearson correlation test was used to analyze the correlation between pretreatment ultrasound parameters and pre-treatment disease activity. All statistical tests were bilateral, with a statistically significant difference of P<0.05. Results:After treatment, the overall score [(1.4±1.0) points vs (6.0±1.8) points, t=17.80, P<0.001], night pain score [(1.6±1.2) points vs (5.7±1.5) points, t=15.80, P<0.001], back pain score [(1.9±1.3) points vs (5.5±1.2) points, t=16.39, P<0.001], morning stiffness [(12±6) min vs (38±21) min points, t=8.93, P<0.001], Bath ankylosing spondylitis disease activity index (BASDAI) [(1.1±0.6) vs (4.6±1.3), t=12.41, P<0.001], ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP) [(1.0±0.4) points vs (3.7±0.9) points, t=22.01, P<0.001] and ASDAS-erythrocyte sedimentation rate (ESR) [(1.0±0.7) points vs (4.0±0.8) points, t=20.10, P<0.001] of patients with ankylosing spondylitis were lower than those before treatment, and the differences were statistically significant ( P<0.001). Compared with AS patients before treatment, the color blood flow grading score was significantly lower after treatment [(1.7±0.8) points vs (3.9±1.1) points, t= 12.86, P<0.001). The post-treatment proportion of AS patients with bilateral sacroiliac joint blood flow signal was 67% (40/60), which was lower than 87% (52/60) before treatment, but the difference was not statistically significant ( P=0.251). After treatment, the peak systolic velocity (PSV), pulsatile index (PI) and resistance index (RI) were significantly higher than those before treatment [(30±17) cm/s vs (19±8) cm/s, t=-5.42, P<0.001; (1.55±0.69) vs (1.00±0.45), t=0.45, P<0.001; (0.81±0.11) vs (0.55±0.14), t=11.20, P<0.001)]. The end diastolic velocity (EDV) before and after treatment had no statistical significant differences [(6.7±2.5) cm/s vs (6.3±1.9) cm/s, t=0.80, P=0.428]. Baseline Doppler ultrasound parameters and pre-treatment clinical indicators showed that PI and RI were negatively correlated with BASDAI ( r=-0.49, P=0.005; r=-0.51, P<0.001) , and blood flow grades were positively correlated with BASDAI ( r=0.46, P=0.028). However, there were no significant correlation between PSV, EDV and BASDAI ( r=-0.12, P=0.176; r=0.03, P=0.756). Baseline Doppler ultrasound parameters were correlated with ASDAS-CRP ( r=-0.45, P=0.012; r=0.29, P<0.048; r=-0.52, P<0.035; r=-0.76, P<0.001; r=0.61, P<0.001). There was no correlation between EDV and ASDAS-ESR ( r=0.30, P=0.110), the other ultrasound Doppler parameters were correlated with ASDAS-ESR ( r=-0.36, P<0.001; r=-0.54, P<0.001; r=-0.61, P=0.021; r=0.41, P=0.028). The receiver operating characteristic curve was drawn with the baseline RI value as a variable. According to the ASDAS-CRP value, the diagnostic threshold for determining the presence or absence of AS activity after 12 weeks of treatment was 0.49, with an area under the curve of 0.817, sensitivity of 88.1%, specificity of 61.1%, positive predictive value of 66.7%, and negative predictive value of 86.1%. Conclusion:Baseline Doppler ultrasound correlates well with clinical indicators, among which baseline RI values is a good predictor of inflammatory activity status after rhTNFR:Fc treatment.
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@#Increasing numbers of edentulous patients and patients with dental defects are willing to accept implant restorations. However, the development of peri-implantitis is a major factor leading to implant failure. The worsening of peri-implantitis promotes the secretion of inflammatory cytokines such as IL-1β and TNF-α and the gene expression of RANKL, inhibits the gene expression of OPG, and increases osteoclast activity, which promotes bone absorption indirectly and leads to a negative balance in bone metabolism. To gain knowledge about the relationship between peri-implantitis and NF-κB signaling pathways, this article summarizes related reports about peri-implantitis and NF-κB signaling pathways, explores the regulatory mechanism by which peri-implantitis affects bone metabolism and NF-κB signaling, discusses the effect of immunological cytokines on NF-κB signaling pathways when inflammation arises, and provides a theoretical foundation for peri-implantitis research and prevention.
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Aim To investigate the effects of curcumol on the contractile activity of isolated duodenal smooth muscle in rats and explore its underlying mechanisms. Methods The isolated duodenum specimens of rats were made. The effects of different concentrations of curcumol on the contraction of isolated duodenal smooth muscle were observed using BL-420F biological and functional experimental system with constant tem-perature perfusion method. A certain concentration of curcumol was combined with atropine,isoproterenol, norepinephrine,calcium-free Krebs solution,verapam-il respectively to observe its effect on smooth muscle contraction. Results Curcumol could stimulate duo-denal smooth muscle in vitro,and increase its contrac-tile amplitude and tension significantly. It could be an-tagonized partly by atropine,isoprenaline,norepineph-rine,verapamil. Conclusion Curcumol can promote the contraction of isolated duodenal smooth muscle in rats,which may be achieved by stimulating M recep-tor,inhibiting α and β receptors,and promoting the extracellular calcium influx.
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Objective:To analyze the impact of Recombinant Human Tumor Necrosis Factor-α Receptor Ⅱ:IgG Fc Fusion Protein (rhTNFR:Fc) on medical insurance budget.Methods:Rheumatic drugs were select from the IMS data 2015.The drug quantity unit was converted to defined daily dose(DDD).The quantity of rhTNFR:FC in IMS data 2015 was taken as the baseline.The expenditure growth and its impact on rheumatic drugs and all drugs were calculated under 90％ and 80％ reimbursement rate as the different incremental proportion of the quantity of rhTNFR:Fc.National health insurance expenditure data was derived from statistical data of government departments.Results:According to 90％ reimbursement rate,medical insurance expenditure increased by 5.22～10.43 billion yuan.rheumatic drugs and all medical insurance drugs expenditure increased by 63.44～126.87％ and 0.04～0.08％ respectively while the consumption of rhTNFR:Fc increased 0-100％ in 2015.The increment of medical insurance expenditure reduced accordingly under the reimbursement ratio of 80％.Conclusion:The budget impact of rhTNFR:Fc was great on medical insurance expenditure of rheumatic drugs,which was very limited on the medical insurance expenditure of all drugs.
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Background Platelet-derived growth facto(PDGF) affectthe proliferation of human lenepithelial cell(LECs),and human LECexpresPDGF-α recepto(PDGFR-α) throughoutheilifetime.The binding of activated PDGF-α receptowith PDGF promotethe synthesiof DNA.Othestudiedemonstrated thasilencing of PDGFR-α by antisense oligodeoxynucleotide(ASODN) inhibitthe growth of RPE cellin proliferative vitreoretinopathy (PVR),buwhethethitechnique ifeasible foLECiunclear.Objective Thistudy wato investigate the effecof the knockdown of the PDGFR-α on the proliferation of human LECin vitro,and to offean experimental basifothe gene therapy of posteriocapsule opacification.MethodHuman LECstrain SRA01/ 04 wacultured in α-MEM containing fetal bovine serum.The cellwere incubated in 6-well platea5 × 104 cells/ well and transfection of ASODN-containing liposome waperformed.The cellwere divided into the blank control group (with blank liposome),PDGFR-α missense oligodeoxynucleotide(MSODN) group (with PDGFR-α MSODN + liposome),0.5 μmol/L PDGFR-α ASODN group (with 0.5 μmol/L PDGFR-α ASODN+liposome) and 1.0 μmol/L PDGFR-α ASODN group (with 1.0 μ mol/L PDGFR-α ASODN+liposome).The morphology of LECwaexamined undean inverse microscope 24 houraftetransfection.The expression of PDGFR-α mRNin the cellwadetected by reverse transcription-PC(RT-PCR).The rate of proliferation (A490) of the cellwaassayed using Mtand the inhibitory rate of PDGFR-α ASODN on proliferation wameasured.The percentage of LECin G1 phase waanalyzed by flow cytometer.ResultThe LECgrew well and exhibited polygonal shape in the blank control group and PDGFR-α MSODN group 24 houraftetransfection.Buin the 0.5 μmol/L and 1.0 μmol/L PDGFR-α ASODN groups,the cellappeared round in shape and the numberof cellwere obviously decreased.The expression of PDGFR-α mRNdetected by RT-Pcdemonstrated highelevel in the blank control group and PDGFR-α MSODN group;however,the PDGFR-α mRNexpression waobviously lowein the 0.5 μmol/L and 1.0 μmol/L PDGFR-α ASODN groups.The A490 value wa0.661 ± 0.036,0.655 ± 0.016,0.529 ± 0.030 and 0.441 ± 0.039 in the blank control group,PDGFR-α MSODN group,0.5 μmol/L PDGFR-α ASODN group and 1.0 μmol/L PDGFR-α ASODN group,respectively,showing significandecline in the 0.5 μmol/L PDGFR-α ASODN group and 1.0 μ mol/L PDGFR-α ASODN group in comparison with the blank control group (F=34.08,P＜0.01).The percentageof LECin G1 phase were (47.73±1.18)％,(49.48±1.09)％,(53.31±1.30)％ and (59.98±0.95) ％ in the blank control group,PDGFR-α MSODN group,0.5 μmol/L PDGFR-α ASODN group and 1.0 μmol/L PDGFR-α ASODN group,showing significandifference among them (F =68.41,P＜0.01),and thain the 0.5 μmol/L PDGFR-α ASODN group o1.0 μmol/L PDGFR-α ASODN group showed significantly increase in comparison with the blank control group (P＜0.05).ConclusionPDGFR-α silencing could inhibithe proliferation of human LECin vitro.
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BackgroundRetinal pigment epithelial(RPE) cells can secrete platelet-derived growth factor (PDGF) and PDGF receptor(PDGFR).Studies have shown that PDGF plays a key role in the formation of proliferative vitreous retinopathy(PVR). ObjectiveThis study was to investigate the proliferation and apoptosis changes of RPE after blockage of the PDGFR-α expression by antisense oligonucleotide ( ASODN ) in vitro. Methods Human RPE cells strain was cultured in low glucose DMEM with 10％ fetal bovine serum.Logarithmic phase cells were collected and incubated in 96-well plate at the density of 5 × 105 cells/hole.PDGFR-α ASODN was transfected into RPE cells at different concentrations for 48 hours.The cells of the blank control group were regularly cultured without any transfection.The changes of PDGFR-α expression were detected by reverse transcription-polymerase chain reaction(RT-PCR),and the proliferation of RPE was detected by MTT as the A490 value.Hoechst 33258 fluorescence staining was used to determine the apoptosis of RPE.Flow cytometry method (FCM) was applied to detect the change of cell cycle and apoptosis rate of RPE cells. ResultsThe A490 values of RPE cells were 1.45±0.12,1.07±0.06,0.65±0.05 in blank control group,1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group with the significant difference(P=0.00 ),and that of 1.0 μmol/L Lipo-ASODN group and 2.0 μ mol/L Lipo-ASODN group were significantly lower than the blank control group ( P =0.00,0.00).Hoechst 33258 staining showed that the apoptosis cells were obviously more in Lipo-ASODN group compared with blank control group.PDGFR-α ASODN transfection induced an increase of percentage of RPE cells in G0/G1 phase( F =206.70,P =0.00),and the apoptosis rates in 1.0 μmol/L Lipo-ASODN group and 2.0 μmol/L Lipo-ASODN group were significantly enhanced in comparison with blank control group ( 37.8 ± 1.3 vs 10.5 ± 0.1,61.2 ± 1.9 vs 10.5 ± 0.1 ) ( F =1808.90,P =0.00 ).Expression intensity of PDGFR-α mRNA in RPE cells in Lipo-ASODN groups was lower. ConclusionsBlocking the PDGFR-α expression with ASODN technology can suppress proliferation and induce apoptosis of RPE cells.Intensity of PDGFR-α mRNA expression in RPE cells is ASODN dose-dependent.ASODN targeted to PDGFR-α offers an experimental basis of the gene therapy for PVR.
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ObjectiveTo evaluate the efficacy and safety of combination therapy of tamsulosin and solifenacin for benign prostatic hyperplasia ( BPH ) with overactive bladder ( OAB ).Methods82 patients with OAB and coexisting BPH were randomly divided into tamsulosin group ( n = 38 ) and combination group ( n = 44). The ages were from 50 to 75 y ( averaged, 56.8 ± 8.6). Inclusion criteria: the mean frequency of micturition ≥8 times per day, the frequency of nocturia ≥2 times per day, voiding volume ＜200 ml each time; for the overactive bladder symptom score ( OA BSS), the 3 rd score ＞ 2, total score ＞ 3. The tamsulosin group accepted tamsulosin 0.2 mg once daily, the combination group accepted tansulouxin 0.2 mg and solifenacin 0.2 mg once daily. Both groups were maintained the corresponding therapy for 12 weeks.The international prostate symptom score (IPSS), Qmax, residual urine volume, OAB score and adverse reactions were recorded.ResultsThe values of IPSS ( 19.5 ±2.2 vs 15.6 ±2.4, P =0.027), the voiding symptom score ( 15.6 ± 2.4 vs 3.4 ± 1. 7, P = 0. 022) and Qmax ( 13.7 ± 3.8 vs 16.6 ± 4.1, P = 0. 034 )improved significantly after treatment in tamsulosin group ( P ＜ 0. 05 ). The values of IPSS ( 19.7 ± 2.3 vs 9.7 ± 3.0, P ＜0. 001), the storage symptom score (13.8 ± 1.9 vs 5.6 ± 1.6, P ＜0. 001 ), OABSS (10.3 ±1.8 vs 5.3 ±1.3, P ＜0.001) and Qmax(14.1 ±4.1 vs 17.2 ±3.5, P=0.027) also improved significantly after treatment in combination group ( P ＜ 0. 05 ). The values of IPSS ( 9.7 ± 3.0 vs 15.6 ±2.4, P ＜ 0.001 ), the storage symptom score (5.6 ± 1.6 vs 12.0 ± 1.6, P ＜ 0.001 ) and OABSS ( 5.3 ±1.3 vs 9.7 ± 2.7, P ＜ 0. 001 ) improved significantly in combination group than those in tamsulosin group ( P ＜0.001 ). There were no difference between two groups in values of the voiding symptom score, Qmax and residual urine volume ( P ＞ 0.05 ). The incidences of adverse reactions in tamsulosin group and combination group were 7.9％ (3/38) and 20.5％ (9/44) without significant difference. There was no acute urinary retention in both groups.ConclusionsIt is effective and safe for patients with BPH and OAB to accept combination therapy of tamsulosin and solifenacin.
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ObjectiveTo evaluate the clinical and radiographic efficacy and safety of the combination of recombinant human tumor necrosis factor-αt receptor Ⅱ IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). MethodsThirty patients with highly active RA were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly). Clinical efficacy was assessed using ACR response criteria and the disease activity score in 28 joints (DAS28).Radiographs of the hands and wrists were assessed with the modified Sharp score. Chi-square test, Fisher is exact test and paired t-test were performed. ResultsAt week 52, ACR20, ACR50 and ACR70 responses were achieved by 90％, 87％ and 67％ respectively. At week 52, mean DAS28 was 3.4±1.1 compared to 6.4±0.6 at base-line(P＜0.01), with 23％ patients achieving clinical remission and 17％ patients in low disease activity. Similarly, the HAQ was improved significantly, declining from 1.18±0.56 at base-line to 0.25t±0.34 at week 52 (P＜0.01). No radiographic progression was found in 22 cases. Adverse events were mild in general.ConclusionTreatment with rhTNFR:Fc plus MTX has shown good efficacy throughout 52 study period in reducing disease activity, improving function, and retarding radiographic progression. Combination therapy for 52 weeks can achieve disease remission and no radiographic progression, which are the two goals of therapy for RA.
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The Nano ultra-high performance liquid chromatography-electrospray ionization mass spectrometry tandem mass spectrometry(UPLC-ESI-MS/MS) was used to characterize the primary protein. Samples were digested by trypsin, followed by liquid chromatography-tandem mass spectrometry analysis and database search. Five peptides matched with tumor necrosis factor receptor and seven peptides matched with human IgG1 fragment of the Fc. Further analysis demonstrated that seven peptides all matched with the IgG1 Fc but only partly peptides matched with the other subtypes. RhTNFR:Fc is fused by IgG1 Fc but not other subtypes.
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Objective Signals in the tumor necrosis factor α TNFα pathway, including TNFα and tumor necrosis factor α receptor 1TNFR1, are upregulated after acute hindlimh ischemia. It is unclear, however, whether this upregulation is apathophysiological consequence or a compensatory response. In the present study, the effect of TNFR1 deletion in a mouse model of hindlimb ischemia was investigated.Methods Hindlimb ischemia was produced through ligation of the proximal and distal left femoral artery and its branches in TNFR1 knockout TNFR1-/- and wild type WT mice. Laser Doppler blood flow measurement showed that limb perfusion was significantly higher in TNFR1-/- mice than that in the WT mice at 1 day after operation.Results The calculated ischemic scores were 3.67 ± 0.52 in WT group and 1.83 ± 0.41 in TNFR1-/- group P ＜0.05. The rate of amputation was 50% in WT mice versus 0% in TNFR1-/- mice. There were less TUNEL positive cells in the calf muscle of TNFR1-/- mice than that of WT mice. Furthermore, DNA fragmentation was more obvious in WT mice.Western blot showed less expression of Bax and cleaved caspase 3 in TNFR1-/- mice 1 day after ischemia, suggesting a reduced apoptotic process in the absence of TNFR1.Conclusion In mice with hindlimb ischemia, knockout of TNFR1 prevents the activation of death-related proteins down streaming to TNF α and attenuated cell death including apoptosis. Systemic block of the TNFR1 might be a new interventional methods-to preserve the limbs from acute ischemic attack in patients with peripheral arterial obstructive disease.