Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Bleeding post-transplantation intrarenal pseudoaneurysms

We herein present a case of an intrarenal pseudoaneurysm developing 2 weeks after renal transplantation. The patient presented with hemorrhagic shock. Computed tomography confirmed an intrarenal pseudoaneurysm with extravasation of contrast and a large surrounding hematoma. Angiography confirmed the pseudoaneurysm, and embolization of the segmental graft renal artery was performed. In view of the uncertain etiology and the possibility of a mycotic pseudoaneurysm, we administered empiric antimicrobial therapy. The clinical course, investigations, and management are described. Finally, a review of the literature regarding post-transplantation pseudoaneurysms is presented. 以下是一宗於移植後 2 週出現的腎內僞動脈瘤個案，患者以出血性休克表現。當時為其安排緊急電腦斷層攝影 (CT)，發現有一個腎內僞動脈瘤，並呈現顯影劑溢出現象，且被一大型血腫圍繞。緊急血管攝影證實為植入腎之僞動脈瘤，同時我們對涉及的節段性動脈予以栓塞處置。基於病因並不明確，而且不能排除黴菌性僞動脈瘤的可能性，因此我們實施了經驗性抗微生物學療法。在本文中，我們描述了本個案的臨床歷程、相關檢查及後續處置，並指出我們在治療上所遭遇到的困難。最後，我們對移植後僞動脈瘤的相關文獻作出了回顧

The pharmacokinetics and bioequivalence of Gengraf and Neoral in stable renal transplant recipients

AbstractObjectiveGengraf capsule, an AB-rated generic cyclosporine for Neoral, has been shown to be bioequivalent in previous studies. The objective of this study was to evaluate the pharmacokinetics and bioequivalence of Gengraf and Neoral in stable Chinese renal allograft recipientsMethodsIn a prospective, open-label, two-period design study, 20 renal allograft recipients receiving stable doses of Neoral were recruited. Subjects continued their Neoral regimen during period I (days 1-14). They were then switched from Neoral on a milligram-for-milligram basis to Gengraf during period II (days 15-28). Four-hour pharmacokinetic parameters (concentration before dosing [Ctrough], maximum blood concentration [Cmax], time to maximum concentration [Tmax], and area under the blood concentration-versus-time curve [AUC0-4]) were taken on days 1, 8, 21, and 28. Biochemical parameters were also evaluated.ResultsThere was no significant difference in the pharmacokinetics of Gengraf (Ctrough, Tmax, Cmax, and AUC0-4) as compared with that of Neoral in stable renal transplant recipients. The bioequivalent capsules were interchangeable with respect to Ctrough, Cmax and AUC0-4. The 90% confidence intervals of the ratio of Ctrough, Cmax, Tmax, and AUC0-4 of Gengraf and Neoral were 0.94 to 1.21 for Ctrough, 0.97 to 1.20 for Cmax, and 0.97 to 1.20 for AUC0-4. Ctrough and C2 remained stable throughout the study without any dosage adjustments. Gengraf was well tolerated, and had a comparable safety profile as Neoral.ConclusionGengraf are bioequivalent to Neoral. Gengraf is well tolerated and interchangeable with Neoral in stable Chinese renal allograft recipients