Cytokine is a key molecular link between chronic inflammation and gallbladder cancer (GBC) progression. The potential mechanism of cytokine-associated modulation of microRNAs (miRNAs) expression in GBC progression is not fully understood. In this study, we investigated the biological effects and prognostic significance of interleukin-6 (IL-6) -induced miRNAs in the development of GBC. We identify that inflammatory cytokine, IL-6 promotes proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GBC both in vitro and in vivo. Among all the changed miRNAs in miRNA profiling, miR-33a expression was significantly decreased in IL-6 treated GBC cell lines, as well as in GBC tissues compared with case-matched normal tissues and cholecystitis tissues. In turn, miR-33a suppresses IL-6−induced tumor metastasis by directly binding Twist which was identified as an EMT marker. High expression of miR-33a suppressed xenograft tumor growth and dissemination in nude mice. The downregulation of miR-33a was closely associated with advanced clinical stage, lymph node metastasis, and poor clinical outcomes in patients with GBC. miR-33a acts as a tumor suppressor miRNA in GBC progression and may be considered for the development of potential therapeutics against GBC.

Type 1 diabetes mellitus (DM) is one of the most common and debilitating diseases to affect the world. Many patients are afflicted by microvascular and macrovascular complications, and succumb to end-stage renal disease (ESRD). Although dialysis and insulin therapy provides better glycemic control, it nonetheless significantly decreases a patient's quality of life. Moreover, they cannot reverse ESRD or alleviate complications. Simultaneous pancreas-kidney (SPK) transplantation has revolutionized the way we manage type 1 DM; it provides a physiological means of achieving normoglycemia while rendering patients free of dialysis. Understanding this procedure is important because it is becoming a more common management strategy for patients with type 1 DM. In this review, we will begin with a brief summary of type 1 DM, followed by a comprehensive description of SPK procedure, including the history and technique. We will then present the outcomes of transplantation.

Abstract. The present study aimed to investigate the expression of interleukin-6 (IL-6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL-6 and epithelial-mesenchymal transition (EMT)-associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, the protein and mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin in 20 GBC tissues were analyzed. The IL-6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E-cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL-6, Twist and Vimentin and underexpression of E-cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor-node-metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL-6, Twist and Vimentin and a reduced expression level of E-cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL-6, Twist and E-cadherin. The increased expression levels of IL-6 and Twist and the reduced expression of E-cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL-6 is associated with EMT-associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC.

Background: Prompt Doppler ultrasonography to aid in diagnosis is often key to managing testicular torsion, but there may be delays in access; a faster, more widely available alternative is point-of-care ultrasonography (POCUS). The purpose of this study was to develop and evaluate a scrotal POCUS curriculum for urology and emergency medicine residents. Methods: Content experts in urology, emergency medicine and diagnostic imaging collaborated in a modified Delphi method to design a practical didactic curriculum for scrotal POCUS for the identification of testicular torsion. Training included 3 online video teaching modules and a 1-hour hands-on teaching session with standardized adult patients. We evaluated participants’ competency in scrotal POCUS using a validated scale. We assessed participants’ knowledge, comfort and confidence in performing scrotal POCUS before and after the intervention and at 3 months. Results: Twenty-four urology (n = 12) and emergency medicine (n = 12) residents participated in the curriculum. After hands-on practice, 23 participants (96%) were deemed competent at scrotal POCUS. Pre–post testing showed significant improvement in knowledge (mean score 63% v. 80%, p < 0.001), comfort (mean Likert score 0.6 v. 3.6, p < 0.001) and confidence (mean Likert score 1.0 v. 2.1, p < 0.001) after the intervention. These effects were maintained at the 3-month assessment. Conclusion: The scrotal POCUS curriculum was effective and acceptable to both urology and emergency medicine residents. The findings suggest that scrotal POCUS can be learned effectively through a short hands-on session and didactic instruction.

BackgroundWhile substantial progress has been made in blocking acute transplant rejection with the advent of immune suppressive drugs, chronic rejection, mediated primarily by recipient antigen presentation, remains a formidable problem in clinical transplantation. We hypothesized that blocking co-stimulatory pathways in the recipient by induction of RNA interference using small interference RNA (siRNA) expression vectors can prolong allogeneic heart graft survival.MethodVectors expressing siRNA specifically targeting CD40 and CD80 were prepared. Recipients (BALB/c mice) were treated with CD40 and/or CD80 siRNA expression vectors via hydrodynamic injection. Control groups were injected with a scrambled siRNA vector and sham treatment (PBS). After treatment, a fully MHC-mismatched (BALB/c to C57/BL6) heart transplantation was performed.ResultAllogeneic heart graft survival (>100 days) was approximately 70% in the mice treated simultaneously with CD40 and CD80 siRNA expression vectors with overall reduction in lymphocyte interstitium infiltration, vascular obstruction, and edema. Hearts transplanted into CD40 or CD80 siRNA vector-treated recipients had an increased graft survival time compared to negative control groups, but did not survive longer than 40 days. In contrast, allogenic hearts transplanted into recipients treated with scrambled siRNA vector and PBS stopped beating within 10–16 days. Real-time PCR (RT-PCR) and flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40 and CD80 expression in splenic dendritic cells of siRNA-treated mice. Functional suppressive activity of splenic dendritic cells (DCs) isolated from tolerant recipients was demonstrated in a mixed lymphocyte reaction (MLR). Furthermore, DCs isolated from CD40- and CD80-treated recipients promoted CD4 + CD25 + FoxP3+ regulatory T cell differentiation in vitro.ConclusionThis study demonstrates that the simultaneous silencing of CD40 and CD80 genes has synergistic effects in preventing allograft rejection, and may therefore have therapeutic potential in clinical transplantation.