Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

[Incidence and predictors of 90-day poor clinical outcome after successful endovascular treatment for acute basilar artery occlusion].

Objective: To investigate the incidence and predictors of 90-day poor clinical outcome after successful endovascular treatment for acute basilar artery occlusion. Methods: Patients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, which was a prospective, multicenter registry study between June 2015 and December 2017. The demographic characteristics, past history, personal history, vital signs, National Institutes of Health Stroke Scale (NIHSS) score, imaging examination, onset/admission/puncture/end of operation, operation-related variables, medication during operation, patency of occluded blood vessels after operation, etiology classification, and 90-day modified Rankin scale (mRS) score were collected. Successful endovascular treatment was defined as modified thrombolysis in cerebral infarction (mTICI) 2b-3. Poor outcome was defined as 90-day mRS 4-6. Multivariate logistic regression analysis was performed to analyze the predictors of poor clinical outcome after successful endovascular treatment. Results: A total of 170 (128 males and 42 females) acute basilar artery occlusion patients undergoing successful endovascular treatment were included in the analysis, with the median age of [M (Q1, Q3)] of 64 (55, 70) years. Poor clinical outcome occurred in 72 patients (42.4%). Multivariate logistic regression analysis revealed that high baseline NIHSS score (OR=1.166, 95%CI: 1.109-1.225, P<0.001) and high baseline systolic blood pressure (OR=1.032, 95%CI: 1.010-1.053, P=0.003) were the independent predictors of poor clinical outcome. Conclusions: The incidence of 90-day poor clinical outcome after successful endovascular treatment for acute basilar artery occlusion is 42.4%. High baseline NIHSS score and systolic blood pressure are associated with the poor clinical outcome.

[Clinical characteristics of 57 patients with polyarteritis nodosa and renal involvement].

Objective: To investigate the clinical characteristics of polyarteritis nodosa (PAN) patients with renal involvement. Methods: PAN patients admitted to the department of rheumatology, department of pediatrics, department of nephrology, general internal medicine department and department of vascular surgery at Peking Union Medical College Hospital from June 2012 to August 2018 were enrolled in this study and were divided into two groups according to renal involvement or not. The clinical characteristics were analyzed. Results: A total of 94 PAN patients were finally enrolled and 57 (60.64%) presented kidney manifestation. The mean age of onset was (37.76±17.40) years old and the interval from onset to diagnosis was 10 (0 to 240) months. Forty patients were misdiagnosed once or more times. In patients with renal involvement, 9 cases suffered from renal ischemia or infarction, 31 with microscopic haematuria, 26 with proteinuria, renal artery or its branch involved in 17 cases, renal vein thrombosis in 1 case, 4 cases with pyeloureterectasis, one case with renal fascia thickening, 33 cases with impaired renal function (serum creatinine>84 µmol/L) including creatinine>140 µmol/L in 10 patients. Renal artery branch stenosis was the most common presentation [9 cases (52.94%)] of renal vascular involvement, other abnormalities including nodular dilatation [4 cases (23.53%)], occlusion [3 cases (17.65%)]. There were significant differences (P<0.05) in the PAN patients with and without renal involvement in the following: age of onset [(33.72±16.13) years vs. (43.97±17.66) years, t(2)=2.901, P=0.005], weight loss(≥4kg since PAN onset) [25(43.86%) vs. 7(18.92%), χ(2)=6.216, P=0.013], elevation of diastolic blood pressure [22(38.60%) vs. 7(18.92%), χ(2)=4.072, P=0.044], acromegaly gangrene [18(31.58%) vs. 21(56.76%), χ(2)=5.859, P=0.015], and gastrointestinal artery involvement [20(35.09%) vs. 6(1.22%), χ(2)=3.993, P=0.046]. Laboratory parameters and the application of glucocorticoid and cyclophosphamide therapies were similar in two groups (all P>0.05). Conclusion: Young PAN patients are more likely to be associated with renal involvement, especially gastrointestinal arteries.

[Endovascular thrombectomy in patients with intracranial large artery occlusion and atrial fibrillation].

Objective: To investigate the safety and efficacy of mechanical thrombectomy in patients with atrial fibrillation complicated with acute intracranial arterial occlusion. Methods: Fifty-eight patients with atrial fibrillation complicated with acute intracranial arterial occlusion in the intervention group of East (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. According to the TOAST (Trial of Org 10 172 in Acute Stroke Treatment) classification, patients were divided into ICAS (Intracranial Atherosclerotic Stenosis) group and cardiogenic embolism group. Clinical characteristics, treatment methods and clinical prognosis were compared between ICAS group and cardiogenic embolism group. Results: A total of 58 patients with atrial fibrillation complicated with acute intracranial arterial occlusion were included in this study, including 46 patients in the cardiogenic embolism group (79%) and 12 patients in the ICAS group (21%). The pre-hospital transport time in ICAS group was longer than that in cardiogenic embolism group (P<0.05).Patency rate in patients with atrial fibrillation complicated with acute intracranial arterial occlusion was 98.3% (57/58), The rate of patients with the 90-day function independent (mRS 0-2) was 51.7% (30/58). There were no statistically significant differences in functional independence, mortality rate, ICH and sICH at 90 days between the cardiogenic embolism group and the ICAS group. Conclusions: Mechanical thrombectomy is an effective method to treat patients with atrial fibrillation complicated with acute intracranial arterial occlusion.

Rutin prevents the ovariectomy-induced osteoporosis in rats.

OBJECTIVE: Our study aimed to explore the anti-osteoporotic effect of rutin (quercetin-3-O-rutinose) on ovariectomized female rats. MATERIALS AND METHODS: An ovariectomized (OVX) rat model of osteoporosis was employed to evaluate the anti-osteoporotic potency of rutin. One week after surgery, the rats were administered intragastrically with rutin or saline once daily respectively for 3 months. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DEXA). The bone microstructure was analyzed by hematoxylin and eosin (HE) staining of the left tibia histomorphology. Estradiol, IL-6, and TNF-α were measured by ELISA kits. RESULTS: The results showed that rutin significantly improved the bone mineral density (BMD) and increased the level of inflammatory factor of IL-6, TNF-α, and INF-γ in OVX rats. Rutin turned bone trabecula to be thickened and dense, and kept regular array. Moreover, rutin significantly improved the average thickness of trabecular bone and the average bone volume fraction. CONCLUSIONS: Rutin possessed with significant anti-osteoporotic activity, which can be considered as an idealistic anti-osteoporotic candidate for human osteoporosis diseases.