ABSTRACT
OBJECTIVE： To evaluate the therapeutic efficacy and safety of 2 kinds of selective Janus kinase 1 （JAK-1） inhibitor Upadacitinib and Filgotinibfor in the treatment of rheumatoid arthritis， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Medline， Embase， the Cochrane library， CBM， CJFD， Wanfang database and VIP， RCTs about placebo （control group） versus Upadacitinib or Filgotinibfor （trial group） in the treatment of rheumatoid arthritis on the basis of methotrexate or other antirheumatic drugs were collected during the establishment of the database to Jan. 2019. Meta-analysis of therapeutic efficacy [the proportion of patients with remission rate of 20％ （ACR20）， ACR50， ACR70 according to the criteria of American Rheumatism Association， the proportion of patients with 28-joint disease activity score （DAS28）＜3.2] and safety [the incidence of adverse event （AE）， severe adverse event （SAE）， infection， severe infection， herpes zoster， liver injury] were conducted by using Rev Man 5.3 software after data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS： A total of 8 RCTs were included， involving 2 738 patients. Meta-analysis showed that the proportion of patients with ACR20 [OR＝3.37，95％CI（2.80，4.05），P＜0.001]， ACR50 [OR＝3.78，95％CI（2.98，4.78），P＜0.001] and ACR70 [OR＝4.31，95％CI（3.05，6.09），P＜0.001]， the proportion of patients with DAS28＜3.2 [OR＝3.86，95％CI（2.98，5.00），P＜0.001]， the incidence of AE [OR＝1.33，95％CI（1.11，1.61）， P＝0.002]， the incidence of infection [OR＝1.43，95％CI（1.12，1.81），P＝0.004] in trial group were significantly higher than control group； there was no statistical significance in other indexes （P＞0.05）. CONCLUSIONS： JAK-1 inhibitors Upadacitinib and Filgotinib can improve the effect indexes of ACR20， ACR50 and ACR70 and the proportion of patients with DAS28＜3.2 of rheumatoid arthritis patients； it can not increase the incidence of SAE， severe infection， herpes zoster， liver injury， but can increase the risk of AE and infection.
ABSTRACT
OBJECTIVE： To evaluate the efficacy and safety of apremilast in the treatment of moderate-to-severe plaque psoriasis systematically. METHODS： Retrieved from PubMed， Embase， Cochrane Library， VIP， CNKI and CBM， RCTs about apremilast or apremilast combined with other drugs （trial group） versus placebo （control group） in the treatment of moderate- to-severe plaque psoriasis were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with bias risk evaluation tool of Cochrane System Evaluator Manual 5.1.0. RESULTS： Totally 7 studies were included， involving 2 332 patients. Results of Meta-analysis showed that case number of psoriasis assessment and severity index （PASI） decreased by 75％ （PASI 75％） [OR＝6.44，95％CI（4.90，8.45），P＜0.000 01]， PASI 90％ [OR＝8.13， 95％CI（4.65， 14.22）， P＜0.000 01] and sPGA 0 or 1 [OR＝3.89，95％CI（3.00，5.05），P＜0.000 01]， the incidence of ADR [OR＝1.87，95％CI（1.44，2.43）， P＜0.000 01] in trial group were significantly more or higher than control group. Subgroup analysis by apremilast dose showed that case number of 20 mg PASI 75％ [OR＝4.72，95％CI（2.77，8.05），P＜0.000 01]， 30 mg PASI 75％ [OR＝7.05，95％CI（5.13，9.69），P＜0.000 01]， 20 mg PASI 90％ [OR＝4.27，95％CI（1.80，10.09），P＝0.001]， 30 mg PASI 90％ [OR＝11.11，95％CI（5.27，23.43），P＜0.000 01]， 20 mg sPGA 0 or 1 [OR＝2.82，95％CI（1.51，5.26），P＝0.001]， 30 mg sPGA 0 or 1 [OR＝4.13，95％CI（3.10，5.50），P＜0.000 01]， the incidence of 30 mg ADR [OR＝1.94，95％CI（1.51，2.49），P＜0.000 01] in trial group were significantly more or higher than control group. There was no statistical significance in the incidence of serious ADR [OR＝1.27，95％CI（0.77，2.07），P＝0.35] or case number of ADR leading to withdrawal [OR＝1.48，95％CI（1.00，2.20），P＝0.05] between 2 groups. CONCLUSIONS： Apremilast is effective for moderate-to-severe plaque psoriasis in dose-dependent manner and improve the quality of life， but increase the incidence of ADR.
ABSTRACT
This study is to report the preparation of complexes of Ad5 and anionic liposomes (AL-Ad5), the amplification of adenoviruses with enhanced green fluorescent protein (eGFP) reporter gene performed by HEK 293 cells, the adenoviral vectors purified by cesium chloride gradient centrifugation, and the titer of adenovirus determined by cytopathic effect (CPE) method, hexon capsid immunoassay and quantitative-PCR (Q-PCR), separately. The prescription and experiment conditions were optimized by central composite design (CCD). The complexes of Ad5 and AL-Ad5 were formulated by the calcium-induced phase change method. The morpholopy, particle size and zeta potential were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. Additionally, the bicolourable fluoresce-labeled complexes (F(labeled)-AL-Ad5) were prepared and their intracellular location in MDCK cells was detected by confocal laser scanning microscopy (CLSM). The results indicate that the complexes of AL-Ad5 exhibited a uniform distribution with a particle size of 211 +/- 10 nm and a zeta potential of -41.2 +/- 2.2 mV. The result of CLSM demonstrates that the intracellular location of red fluoresce-labeled adenovirus was consistent with that of green fluoresce-labeled liposomes suggesting that the naked adenovirus was well encapsulated by the anionic liposomes in complexes of AL-Ad5.