Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Research advances of tofacitinib in the treatment of ulcerative colitis / 中国药房

Ulcerative colitis （UC）is a chronic inflammatory bowel disease caused by multiple factors ，and its etiology and pathogenesis remain unclear . Tofacitinib，a small molecule rapidly absorbed by oral administration ，treats UC primarily by inhibiting Janus kinase （JAK）. Tofacitinib has been approved by the FDA and the European Medicines Agency for the treatment of moderate to severe UC . Many clinical studies on tofacitinib in the treatment of UC have been carried out abroad ，but there is no relevant report on its use in UC in China . This paper summarizes the relevant research advances of tofacitinib in the treatment of UC from its mechanism ，clinical application and safety . The results show that tefatinib mainly treats UC by inhibiting the expression of JAK and proinflammatory factors , regulating the overexpressed signaling transducers and activators of transcription , and repairing the intestinal mucosal barrier . Tofacitinib has good clinical efficacy ，but safety studies have shown that the risks of herpes zoster and thrombosis should not be ignored ，and the drug should be used with caution in pregnant ，children，adolescents， and elderly patients . The efficacy and safety of tofacitinib in Chinese population should be further studied in the future ，since it has not been used in UC patients in China .

Progress in Studies on Diagnosis and Surgical Treatment of Refractory Ulcerative Colitis / 胃肠病学

Ulcerative colitis (UC) is a chronic immune-mediated gastrointestinal inflammatory disease, the etiology has not been fully clarified. As a developing and emerging industrialized country, China is about to enter or has entered the stage of ' accelerated incidence rate and compound epidemic' of UC. Evaluate the clinical condition of refractory ulcerative colitis (RUC) at its early stage and select appropriate treatment is important. Although the kinds of drug become more and more, the rate of colon resection remains unchanged. When drug therapy cannot improve the symptoms of patient, surgical treatment should be considered. This article reviewed the progress in studies on diagnosis and surgical treatment of RUC.

Visual improvement of therapeutic plasma exchange for refractory optic neuritis patients in acute phase / 中华眼底病杂志

Objective To evaluate the visual improvement of therapeutic plasma exchange (TPE) for refractory optic neuritis (ON) patients in acute phase.Methods Seventy-five affected eyes from 44 refractory ON patients with severe visual defect or resistance to high-dose intravenous methylprednisolone (IVMP) therapy,who were admitted to The Chinese PLA General Hospital between January 2015 and August 2016,were recruited and received TPE therapy.Among these patients,11 were male and 33 were female;the average age was 39.1 ± 13.9;31 patients had two affected eyes,13 patients had one affected eye.The course of the disease on the group of patients were more than 2 weeks,and the visual acuity worsened for more than 10 days and continued to deteriorate.TPE treatment was performed on all of the patients.BCVA was recorded before and 24 h after treatment,and the visual function was scored using visual outcome scale (VOS).At the same time,the adverse reactions of TPE treatment were observed.The paired t-test was used to compare the VOS before and after treatment.The correlation between VOS before and after treatment was analyzed by Linear-by-Linear correlation analysis.Results Among 75 affected eyes,the post-therapy VOS 3.89 ±2.13 was significantly improved from pre-therapy VOS 5.56± 1.69 (t=6.77,P＜0.001).Forty-eight of 75 eyes were improved at lease 1 score of VOS,the overall rate of visual improvement was 64.0％.Especially among the eyes with initial vision of light perception,an improved rate of 82.4％ was presented.75.0％ in those eyes with initial vision of count fingers and 67.7％ in no light perception.Linear-by-Linear correlation analysis showed a significant linear correlation between the scores of VOS before and after TPE treatment (r=0.398,P=0.01).During the course of TPE treatment,5 patients had mild adverse reactions such as low calcium reaction and allergic reaction and were well controlled after treatment.Conclusion Using TPE to treat refractory ON in acute phased can improve the visual function of patients.