Functional recovery of denervated muscle by neurotization using nerve guidance channels

Tissue‐engineered muscle has been proposed as a means of repairing volumetric muscle defects to restore anatomical and functional recovery. We have previously demonstrated that denervated muscle, which is analogous to engineered muscle construct, can be reinnervated by direct transplantation of host nerve (neurotization) in a rat model. However, the use of this approach is not possible if the length of host nerve is inadequate and cannot be mobilized to the insertion site of the engineered muscle. In this study we investigated whether neurotization coupled with nerve guidance channels would increase the regeneration of neuromuscular junctions (NMJs) in completely denervated muscle and encourage neurofunctional recovery. Seventy‐two Lewis rats were evaluated in three groups, a normal control group (n = 8), a denervated group (n = 32) and a neurotization coupled with nerve guidance group (n = 32). Neurofunctional behaviour and histological evaluations were performed at 4, 8, 12 and 20 weeks postoperatively. Extensor postural thrust (EPT) and compound muscle action potential (CMAP) amplitude were significantly improved in the nerve guidance group when compared with the denervated group, even though these values were different from those of the normal control group at 20 weeks postoperation. Regeneration of axons and NMJs was demonstrated histologically in the nerve guidance group. Neurotization coupled with nerve guidance channels leads to regeneration of axons and NMJs in completely denervated muscle. To our knowledge, this is the first report to show that nerve guidance can allow re‐innervation in denervated muscle containing long‐gap nerve injuries. Copyright © 2013 John Wiley & Sons, Ltd.     

Upgrading and upstaging of low-risk prostate cancer among Korean patients: a multicenter study

Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy (41.6%–50.6%). We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a “worsening prognosis” as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 (47.5%) patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level (odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007–1.271; P= 0.037), percent positive biopsy core (OR: 1.018; 95% CI: 1.002–1.035; P= 0.032), and small prostate volume (≤30 ml) (OR: 2.280; 95% CI: 1.351–3.848; P= 0.002) were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort.     

大鼠慢性前列腺炎模型中TRPA1及相关炎症因子的表达

目的:探讨模拟慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)动物模型疼痛产生的分子机制。方法:取SD大鼠36只,随机分为实验组和对照组,每组18只。实验组向前列腺双腹侧叶注射50μl 3%无菌λ-角叉菜胶制作大鼠无菌性前列腺炎症性疼痛模型,对照组注射等量无菌生理盐水。两组分别于造模后1周、2周和4周3个时间节点,每个节点6只大鼠,解剖获取大鼠前列腺组织、L6~S1段背根神经节(DRG)及脊髓,采用免疫组化联合Western印迹法检测神经生长因子(NGF)、瞬时受体电位通道蛋白A1(TRPA1)及降钙素基因相关肽(CGRP)在不同组织内的表达情况。结果:慢性前列腺炎症性疼痛大鼠前列腺组织中NGF、CGRP、TRPA1蛋白的表达均高于对照组(P<0.05),且随造模时间的延长各蛋白表达逐渐减弱,组间比较差异有统计学意义(P<0.05)。在大鼠L6~S1段DRG及脊髓内,造模后1周,实验组NGF、CGRP及TRPA1表达与对照组比较差异无统计学意义(P>0.05),造模后2周及4周,各蛋白表达呈持续高水平状态,与造模后1周大鼠比较差异无统计意义(P>0.05),但各实验组大鼠与对照组蛋白表达比较差异均有统计学意义(P<0.05),两时间点上两组蛋白表达比较差异无统计学意义(P>0.05)。结论:前列腺内注射λ-角叉菜胶方法制作的大鼠前列腺炎症性疼痛模型,可在分子水平模拟CP/CPPS的产生机制;TRPA1在CP/CPPS患者疼痛产生上可能发挥中继通道的作用。     

Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

Purpose: To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods: Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F (18 patients), the patients were treated with fondaparinux sodium, 2.5 mg, 1/d for 11 d. In group L (18 patients), the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome (MODS) and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin III were measured by the coagulation analyzer. Results: The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L (p < 0.05). Antithrombin III got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and 11th d (p<0.05). Fibrinogen levels were gradually increased, and there was no significant difference between two groups (p>0.05). D-dimer was significantly decreased after anticoagulant therapy for 5 d (p<0.01), and there were significant differences between two groups on the 5th d and 7th d (p < 0.05). It showed no significant difference on the 11th d (p>0.05). Conclusion: Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.     

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88^−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b⁻Gr-1⁺ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88^−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88^−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88^−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.