ABSTRACT
Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.
ABSTRACT
Type Ⅰ interferonopathies is a relatively new group of diseases in the last decade, which belong to auto-inflammatory disorders characterized by robust inflammation.Its low incidence and diverse clinical manifestations make it difficult for the clinical identification and diagnosis of this disease.In this article, the concept, pathogenesis, diagnosis and treatment options of this disease was introduced briefly, in order to enhance clinicians′ knowledge of them, thus achieving the goal of early recognition, early detection, early identification and early intervention for the benefit of more patients and their families.
ABSTRACT
OBJECTIVE：To systematically evaluate the efficacy and safety of pe ficitinib for treating rheumatoid arthritis （RA），and to provide evidence-based reference for the clinical treatment of RA. METHODS ：Retrieved from PubMed ，Embase， The Cochrane Library ，CJFD，VIP and Wanfang database during from their establishment to September 2019，randomized controlled trials （RCTs）about the efficacy and safety of Peficitinib （trial group ）versus placebo （control group ）in the treatment of RA were collected. The risk of bias assessment tool provided in Cochrane System Evaluator Manual 5.1.0 was used to evaluate the quality after data extracted from clinical studies which met the inclusion criteria. Meta-analysis of the efficacy [the proportion of patients who met the American College of Rheumatology 20％ improvement criteria （ACR20），ACR50，ACR70，the proportion of the patients with 28 joint disease activity index ＜2.6 calculated by erythrocyte sedimentation rate （DAS28-ESR＜2.6），the proportion of patients with 28 joint disease activity index ＜2.6 calculated by C-reactive protein （DAS28-CRP＜2.6），etc.] and safety（incidence of total ADR ）was performed by using Stata 16 statistical software. RESULTS ：Totally 5 RCTs were included ， 药学。E-mail：hyl3160131@163.com 5.11），P＜0.001]，150 mg[RR＝3.52，95％CI（1.78，6.96），P＜ 0.001]}，ACR70{total [RR ＝2.51，95％CI（1.52，4.14），P＜0.001]，100 mg[RR＝3.50，95％CI（1.62，7.58），P＝0.001]，150 mg [RR＝4.59，95％CI（1.47，14.30），P＝0.009]}，DAS28-ESR＜2.6{total [RR ＝4.83，95％CI（3.20，7.28），P＜0.001]，100 mg[RR＝ 5.37，95％CI（2.68，10.77），P＜0.001]，150 mg[RR＝7.44，95％CI（3.78，14.65），P＜0.001]} and DAS 28-CRP＜2.6{total [RR ＝3.41， 95％CI（2.65，4.39），P＜0.001]，100 mg[RR＝4.00，95％CI（2.67，5.99），P＜0.001]，150 mg[RR＝4.45，95％CI（2.99，6.63），P＜ 0.001]} in trial group were significantly higher than control group ，with statistical significance. In term of safety ，there was no statistical significance in the incidence of total ADR [RR ＝1.05，95％ CI（0.94，1.16），P＝0.395] between 2 groups. CONCLUSIONS：For the treatment of RA ，100 mg or 150 mg peficitinib once per day is superior to placebo in terms of ACR 20， ACR50 and ACR 70，DAS28-ESR＜2.6，DAS28-CRP＜2.6； the adverse events are mild and tolerable and it may be a new treatment option for RA.
ABSTRACT
The knowledge and understanding of myeloproliferative neoplasms (MPN) over the last hundred years has been reviewed in this article,focusing on clinical practice.The identification of JAK2 V617F gene mutation leads Philadelphia chromosome-negative (Ph) MPN into a new era of molecular biology.These advances not only provide a reliable diagnostic tool and important evidence for diagnosis of MPN,also induce a lot of investigation and manufacture of targeting drugs to JAK2 mutation.However,JAK2 V617F mutation is not the gold standard for the diagnosis of MPN,as unique as bcr-abl in CML.Certain routine lab results and differentiation with some other diseases are still necessary.A JAK1/JAK2 inhibitor,ruxolitinib,has been approved for clinical use,but indication should be followed.Further follow-up is needed to assess the longterm outcomes with respect to efficacy and safety.It is not time to give up conventional medicine,such as hydroxyurea or aspirin.