Mesh meta-analysis of the efficacy of original and biosimilar TNF-α inhibitors in the treatment of ankylosing spondylitis / 中华风湿病学杂志

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.

Clinical features and prognosis of lymphoma patients with monoclonal immunoglobulin / 白血病·淋巴瘤

Objective:To analyze the clinical features and prognosis of lymphoma patients with monoclonal immunoglobulin (McIg).Methods:The data of 14 patients who were pathologically diagnosed as lymphoma and with McIg in the First Affiliated Hospital of Fujian Medical University from January 2014 to January 2019 were retrospective analyzed. At the same time, 40 lymphoma patients without McIg were sellected as controls. The patients'age, gender, international prognostic index (IPI) score, B symptoms, tumor cell source and Ki-67 index were analyzed by prognostic single factor analysis. Kaplan-Meier method was used for survival analysis, and the overall survival (OS) and progression-free survival (PFS) were compared between the two groups.Results:Among 14 lymphoma patients with McIg, 6 were males and 8 were females. The median age of onset was 63 years (42-78 years). There were 13 cases of clinical stage Ⅲ-Ⅳ, and 12 cases of extranodal disease. The most common type was IgM-κ. The results of univariate analysis showed that IPI score≥3 points and elevated D-dimer level were related to poor prognosis (both P < 0.05). At the end of follow-up, the median OS time of lymphoma patients with McIg had not reached, the 2-year OS rate was 64.3%, and the median PFS time was 16 months; the median OS time of lymphoma patients without McIg had not reached, the 2-year OS rate was 90.8%, and the median PFS time was 37 months; the difference of OS between the two groups was statistically significant ( P = 0.040). Conclusions:Most lymphoma patients with McIg have extranodal involvement, the clinical stage is more inclined to stage Ⅲ-Ⅳ, IPI score ≥3 points and elevated D-dimer level are poor prognostic factors. The secretion of McIg is an important factor for the poor prognosis of patients with lymphoma.

Mutations of vitamin D receptor gene found in patients with multiple myeloma / 中华肿瘤杂志

Objective@#To explore the mutations of vitamin D receptor (VDR) gene in patients with multiple myeloma (MM).@*Methods@#Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the mutations of VDR gene(loci Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ, Taq Ⅰ) in forty MM cases and 84 healthy control subjects.@*Results@#A synonymous mutation (ATC→ATA , both encode isoleucine) at cDNA codon1421 of VDR gene was found in one MM patients, which correlated to a better therapeutic response. Rare Bsm Ⅰ AA genotype and Taq Ⅰ CC genotype were detected in a MM patient, which might be related to the relapsing and refracfory disease. Meanwhile, a rare allele(rs201747972, global MAF: A=0.0005/1), was found in another MM patient, which might be related to MM cell lines of two origins. rs11574113 G>C, rs2229829 C>A and rs201747972 C>T polymorphic loci(the same as Fok Ⅰ, Bsm Ⅰ, Apa Ⅰ and Taq Ⅰ) were found in a MM patient, which were associated with nonsense-mediated mRNA decay(NMD), contributing to the onset of MM.@*Conclusions@#A new synonymous mutation, rare genotype, rare allele and new SNP are found in this study. These data enrich the genetic information of MM in China, and are helpful for the further research on MM pathogenesis.

Cell-specific expression of the diphtheria toxin A-chain coding sequence induces cancer cell suicide / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To test whether the diphtheria toxin A (DT-A) chain coding sequence linked to murine immunoglobulin Kappa light chain (IgKappa) promoter and enhancer have selective cytocidal effects on IgKappa producing cells.</p><p><b>METHODS</b>The diphtheria toxin A gene or beta galactosidase (beta-gal) gene were linked to a murine IgKappa promoter and enhancer to construct pcDNA3IgKappaDTA or pcDNA3IgKappaLacZ plasmids. These plasmids were transfected into IgKappa producing or non-producing cells by the liposome coated DNA method. Expression of beta-gal activity and effects on cell growth of transfected cells were assessed.</p><p><b>RESULTS</b>The beta-gal gene, under the control of cytomegalovirus (CMV) promoter, can express in all cell lines. Expression of beta-gal under the control of the IgKappa promoter was detected only in the IgKappa producing cell line, CA46. Expression of beta-gal was greatly suppressed when cotransfected with pcDNA3IgKappaDTA in CA46 cells. Cell growth of CA46 cells transfected with pcDNA3IgKappaDTA plasmid was significantly inhibited compared with CA46 cells transfected with pcDNA3IgKappaLacZ.</p><p><b>CONCLUSION</b>Selective killing of IgKappa producing cells can be attained by introducing the diphtheria toxin A gene under the control of IgKappa promoter and enhancer.</p>