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Objective:In order to understand the difference of clinical efficacy between original TNF-α inhibitors (TNFi) and their biosimilars, Bayesian mesh Meta-analysis was compare Etanercept, Infliximab, Adalimumab with their biosimilars in the treatment of ankylosing spondylitis (AS).Methods:A systematic literature search was performed, using Ovid Biomedical, Embase, Cochrane Library, CNKI, Wanfang Database and Weipu Database (up to March 8, 2023 for all resources above), to search publications of randomized controlled trial (RCT) about all original and biosimilar TNFi for the treatment of AS in all language. Two reviewers independently identified the eligible trails, evaluated bias risk and extracted relevant data. Based on Bayesian network, data analysis of included studies was conducted using statistical software R3.6.1 and R Studio.Results:The results of the network meta-analysis showed that, no significant differences was observed among. Etanercept, Infliximab,Adalimumab, and their biosimilars for ASAS20 when Infliximab was compared with Etanercept [ OR (95% CI)=1.4 (0.54, 3.5)], placebo was compared with Etanercept [ OR (95% CI)=0.35 (0.17,0.67)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASDAI, when Infliximab was compared with Ctanercept [ OR (95% CI)=-0.89 (-1.8, 0.081)], placebo was compared with Etanercept [ OR(95% CI)=1.7(0.86, 2.5)], No significant differences were observed among Etanercept, Infliximab, Adalimumab, and their biosimilars for BASFI, when Infliximab was compared with Etanercept [ OR(95% CI)=-0.46(-1.3, 0.47)], placebo was compared with Etanercept [ OR(95% CI)=1.6(0.8, 2.3)]. Conclusion:Etanercept, Infliximab, Adalimumab with their biosimilars are significantly superior to placebo and sulfasalazine in terms of ASAS20, BASDAI, BASFI, CRP, ESR. Limited evidence have shown that the efficacy of biological biosimilars are similar to that of their corresponding original drugs.
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Objective To evaluate the efficacy and safety of glucosamine (GS) combined with chondroitin sulfate (CS) for knee osteoarthritis (OA).Methods We searched the CENTRAL (Issue 1,2016),PUBMED (1946 to 2016.1.20),EMBASE (1947 to 2016.1.20),CBM (1978 to 2016.1.20),CNKI (1994 to 2016.1.20),WanFang Data (1980 to 2016.1.20) and VIP (1989 to 2016.1.20) and we searched randomized controlled trials (RCT) of GS combined with CS for knee OA.Two reviewers independently identified the included trials,evaluated the quality of methodology and extracted data.The Review manager 5.3 software was used for data analysis.Results Four RCTs were included in this systematic review.The combination group compared with GS group,a total number of 1 145 patients,and the combination group compared with CS group,a total number of 1 067 patients.The outcomes showed:① Among those 4 RCTs that comparing the combination with GS,three RCTs reported western ontario and mcmaster universities osteoarthritis index (WOMAC) score.Summarized results of these 3 RCTs showed no significant difference between combination group and GS group (all P values ＞0.05).MDs of WOMAC score in pain,stiffnessand function were-6.60[95％CI(-18.79,5.59),-15.90(-43.09,11.29) and-6.44 (-16.46,3.59)].② Two long-term (≥6 months) study (n=937) compared the combination with CS group and showed no significant difference (all P values ＞0.05).Pooled MD of WOMAC score in pain and function were-0.80 (-4.96,3.36) and-1.76 (-4.46,0.94) respectively.③ Subgroup analysis in 1 RCT showed that in moderate-to-severe knee pain group (n=142) combination obviously improve the WOMAC score in pain,stiffnessand function compared with CS groupand the differences werestatistically significant (all P values ＜0.05).MDs were-10.46(-17.98,-2.94),-9.70(-18.48,0.92) and 9.39 (-17.33,-1.45).Conclusion There is no evidence to support that the combination of GS and CS for knee OA cansignificantlyimprovethe WOMAC score compared with either GS or CS.For patients with-moderate-to-severe knee pain,combination might be superior toeither GS or CS.
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6-sulfo LacNAc dendritic cells (slanDCs),characterized by expressing the Fc receptors that absent in classic dendritic cells (DCs),have been identified as a novel subgroup of peripheral blood DCs.Hitherto,the majority researches of slanDCs are about inflammation and autoimmunity diseases,but a growing body of literature has shown that slanDCs may play important roles in anti-tumor immunity by inducing antibody-dependent cell-mediated cytotoxicity,releasing special cytokines,cross-talking with mesenchymal stem cells or natural killer cells,and signal transduction through Toll-like receptor pathway and mitogen-activated protein kinase pathway.slanDCs may be an ideal anti-tumor therapy tool.
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Objective To explore the clinical features of sentinel polyps (rectal polyps with proximal colon carcinoma), and the correlation between sentinel polyps and proximal colon carcinoma. Methods The clinical data of 331 patients with rectal polyps were retrospectively analyzed. According to the combination condition of proximal colon carcinoma, the patients were divided into sentinel polyps group (observation group, 37 cases) and pure rectal polyps group (control group, 294 cases). The family history, laboratory examination, colonoscopy, clinical pathological features, treatment, sequelae and short-term prognosis were compared between 2 groups. Results The family history rate, positive rate of tumor marker and the incidences of polyps maximum diameter>1 cm, polyps>5 pieces, adenomatous polyp in observation group were significantly higher than those in control group:35.1%(13/37) vs. 4.8%(14/294), 67.6%(25/37) vs. 6.8%(20/294), 62.2%(23/37) vs. 46.6%(137/294), 43.2%(16/37) vs. 11.9%(35/294) and 83.8%(31/37) vs. 35.4%(104/294), and there were statistical differences (P<0.01). The patients in control group did not have special find in colonoscopy. The majority patients in observation group had new organisms around the lumen growth in colonoscopy, but the intestinal canal between rectal polyps and proximal colon carcinoma did not have special find. The majority pathologic type of proximal colon carcinoma patients in observation group was papillary adenoearcinoma and tubular adenocarcinoma, 75.7%(28/37). Duke stage:A stage was in 11 cases (29.7%, 11/37), B stage in 11 cases (29.7%, 11/37), C stage in 9 cases (24.3%, 9/37), and D stage in 6 cases (16.2%, 6/37). In control group, 282 patients (95.9%, 282/294) were treated by endoscope, and they were cured and discharged. In observation group, 15 patients (40.5%, 15/37) were treated with radical operation, 9 patients (24.3%, 9/37) by endoscope, 7 patients (18.9%, 7/37) with palliative surgery, 4 patients (10.8%, 4/37) with chemotherapy, and 2 patients (5.4%, 2/37) with symptomatic treatment;the patients were followed up for 6-12 months, the 23 patients with complete tumor resection did not relapse, 12 patients showed tumor reduction or symptomatic relief, and the other 2 patients died. Conclusions If maximum diameter over 1 cm, multiple and adenomatous polyps exist, the possibility of carcinogenesis of the polyps or the proximal colon should be awared. The patients should be followed up in short-term and complete the whole colon examination.
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Objective:To explore the role of γδ T cells in the transdifferentiation of immature dendritic cells(imDC) into osteoclasts(OC). Methods:(1) Peripheral blood mononuclear cells(PBMNC) were cultured with zoledronate(Zol) and recombinant human interleukin-2(IL-2),and PBMNC from healthy volunteers were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) and recombinant human interleukin-4(IL-4) to differentiate into imDC,which were then cultured with receptor activator nuclear factor к B ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) to differentiate into OC. The purity of γδ T cells,and phenotype changing of OC transdifferentiated from imDC were investigated by flow cytometry. (2) Co-culture system was es-tablished using millicell inserts.γδT cells isolated with immune magnetic bead were placed in the upper compartment and imDC in the lower compartment in the ratio of 10∶1. To explore the role of γδ T cells during differentiation of imDC into OC,tartrate resistant acid phosphatase( TRAP) staining and bone resorption observation staining were used. Tumor necrosis factor-alpha( TNF-α) of supernatant liquid from different cultures was measured using ELISA(Enzyme linked immunosorbent assay) kit. Results:(1) γδT cells can be ex-panded from PBMNC of MM patients, and the production capacity was similar to that of healthy volunteers ( 68. 87%± 20. 94% vs 69. 33%±16. 84%,P>0. 05 ) . ( 2 ) OC could be transdifferentiated from imDC when cultured with RANKL and M-CSF. ( 3 ) The number of TRAP+ multinuclear cell and the absorption area of dentine were significantly lower in the group of imDC indirectly co-cultured with γδ T cells than in the group of control imDC(5.67±0.58 vs 28.33±2.08,4.97%±4.3% vs 28.47%±12.8%, respectively). (4) Under the circumstance of γδ T cell-imDC indirect coculture,TNF-α got significantly higher. Conclusion: γδ T cells might inhibit the transdifferentiation of imDC into OC.γδ T cells-based immunotherapy is expected to be a new treatment for myeloma bone disease.
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Objective To evaluate the efficacy and safety of combination chemotherapy with vinorelbine and cisplatin in the treatment of metastatic breast cancer resisting to anthracycline and taxane.Methods 20 patients with advanced metastatic breast cancer were given following regimen:Vinorelbine 25mg/m2 was given intraveniously in day 1 and day 8,cisplatin 75mg/m2 was given intraveniously in day 1 or 25mg/m2 was given intraveniously in day1 to day 3,repeated every 3 weeks.Evaluation of response and adverse reactions were practiced every 2 cycles.Results 20 patients were evaluable,among them,2 cases reach CR,8 cases PR,4 cases SD and 6 cases PD,with a median followup of 6 months(4 ～ 18months),16 patients survived and 4 patients died.The median time to progression and the median survival time was 5 months(3 ～ 15 months) and 8 months(4 ～ 18 months) respectively.The treatment well tolerated,The main toxicity was myelosuppression and gastrointestinal reaction with WHO grade Ⅲ～Ⅳ gastrointestinal reaction,neutropena and thrombocytopenia being in 25% 、65% and 10% .Conclusion The regimen of NP is safe and effective in treating advanced metastatic breast cancer resisting to anthracycline and taxane.In addition,it was able to improve survival rate and adverse reactions could be tolerated.
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Objective To investigate the number of osteoclast (OC) precursor in the peripheral blood of patients with ankylosing spondylitis (AS) and its relationship with serum receptor activator of nuclear factor KB-ligand (RANKL) and Osteoprotegerin (OPG) concentration as well as the disease activity. Methods The peripheral blood mononuclear cells from 8 cases of AS patients and 5 healthy controls were cultured in the medium containing macrophage colony-stimulating factor (M-CSF) (25 ng/ml) and RANKL (40 ng/ml). After being cultured for 14 days, cytochemistry was applied to detect tartrate-resistant acid phosphatase (TRAP) expression and the cells with TRAP expression and ≥3 nuclei were counted and defined as OC. Bone resorption assay was used to demonstrate OC function. ELISA was used to measure serum RANKL and OPG concentration in 23 cases of AS and 17 healthy controls. The relationship was analyzed in AS patients between the number of OC precursors and serum RANKL and OPG concentration as well as the disease activity. The indicators of disease activity were Bath ankylosing spondylitis disease activity index (BASDAI), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). T test, t' test and Spearman correlation were selec-ted. Results ① Significantly higher OC production was observed in the peripheral blood of AS patients than that of healthy control group. The OC number per ten fields was 10.9±3.4 and 6.2±1.3 respectively (P<0.05); ② There was significant difference between AS patients and healthy controls in serum concentration of OPG and RANKL and the ratio of RANKL/OPG. OPG was significantly higher in AS patients [(157±49) pg/ml] than in healthy controls [(105±20) pg/ml] (P<0.05). RANKL was significantly higher in AS patients [(5.4± 3.8) pg/ml] than in healthy controls [(1.6±0.8) pg/ml] (P<0.05). The ratio of RANKL/OPG was significantly higher in AS patients (0.037±0.026) than in healthy controls (0.016±0.008) (P<0.01 );③Significantly positive correlation was observed between the OC number and the serum concentration of RANKL (r=0.692, P=0.009), the ratio of RANKL/OPG (r=0.813, P=0.001);④ In AS patients, serum concentration of OPG was found to have significantly negative correlation with BASDAI (r=-0.444, P=0.044). Serum RANKL concentration was found to have significantly positive correlation with BASDAI (r=0.543, P=0.011). The ratio of RANKL/OPG was found to have significantly positive correlation with BASDAI (r=0.672, P=0.001). Conclusion ① More OC precursors exist in the peripheral blood of AS patients. These cells may differentiate into osteoclasts, which might play a role in joints destructions in AS;② The mechanism of high OC production is likely to be due to high RANKL concentration which is caused by inflammatory reaction.
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Objective To investigate the association between tumor necrosis factor ? (TNF ?) gene polymorphism and ankylosing spondylitis (AS).Methods Genomic DNA from 98 Chinese AS patients and 70 ethnically matched controls were typed for TNF(308) polymorphism by allele specific polymerase chain reaction (AS PCR).Results The TNF genotypes in AS patients were respectively TNF1 homozygote 37%,TNF2 homozygote 10% and TNF1 and TNF2 heterozygote 53%.While TNF genotypes in controls group were respectively TNF1 homozygote 67%,TNF2 homozygote 3% and TNF1 and TNF2 heterozygote 30%.Significant difference was found in the distribution of TNF 308 genotype between both groups ( ? 2=15 73, P
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Objective:To explore the methods and condition in which calcium ionorphore(CI) induces the CML cells to differentiate into dendritic cells(DCs).Methods:Mononuclear cells were separated from peripheral blood or bone marrow of CML patients whose WBC counts were more than 30?30~9 L~ -1 when samples were collected,then lymphocytes and monocytes were discarded by pouring out supernatant twice at different culture time point. Slightly adherent cells were cultured in RPMI1640 containing 10%FCS(Fetal calf serum),with or without CI(375 ng/ml) and GM-CSF(200 ng/ml) at 37℃,5%CO_2 humidified atmosphere for 96 h. To evaluate the effect of CI on inducing CML cells to differentiate into DCs,the phenotype of these cells were analyzed by flow cytometry and the morphology change was observed under inverted microscope and electron microscope. Better condition was also explored for DCs differentiation from CML cells under the effect of CI.Results:After 96 h of culture with CI and GM-CSF,the CML cells acquired morphology of mature DCs and significantly up-regulation of CD80,CD86,CD40,CD86 and HLA-DR.Conclusion:CML cells might acquire typical morphology and immunological phenotype of mature DCs when being cultured with CI and GM-CSF.
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Objective:To investigate the effect of calcium ionorphore on B7 costimulatory molecules of chronic myeloid leukemia cells line K562.Methods:Well growing K562 cells were cultured in the medium containing calcium ionorphore(375 ng/ml),with K562 cells without CI treatment as control.The cells′ viability and number were calculated by Trypan Blue exclusion at 0,48 and 96 h.Before and after 96 h of cultured,B7-1 and B7-2 expression was assayed by flow cytometry.The proliferation of allogeneic human T cells was measured by MTT colorimetry.Results:B7 costimulatory molecules were abcent or lowly expressed on K562 cells.After 96 h of CI treatment,B7 costimulatory molecules of K562 cells were markedly upregulated and marked activation of allogeneic T cells occurred.No notable morphological change was found during the culture.K562 cells cultured in medium with CI grow slowly than that without CI.Conclusion:B7 costimulatory molecules expression on chronic myeloid leukemia cells line K562 surface was defective.These costimulatory molecules on K562 cells can be upregulated by calcium ionorphore.Calcium ionorphore may inhibit the growth of K562 cells.