Reproducibility (test–retest) of vestibular evoked myogenic potential

IntroductionThere is still no consensus in the literature as to the best acoustic stimulus for capturing vestibular evoked myogenic potential (VEMP). Low-frequency tone bursts are generally more effective than high-frequency, but recent studies still use clicks. Reproducibility is an important analytical parameter to observe the reliability of responses.ObjectiveTo determine the reproducibility of p13 and n23 latency and amplitude of the VEMP for stimuli with different tone-burst frequencies, and to define the best test frequency.MethodsCross-sectional cohort study. VEMP was captured in 156 ears, on the sternocleidomastoid muscle, using 100 tone-burst stimuli at frequencies of 250, 500, 1000, and 2000 Hz, and sound intensity of 95 dB nHL. Responses were replicated, that is, recorded three times on each side.ResultsNo significant difference was observed for p13 and n23 latencies of the VEMP, captured at three moments with tone-burst stimuli at 250, 500, and 1000 Hz. Only the frequency of 2000 Hz showed a difference between captures of this potential (p < 0.001). p13 and n23 amplitude analysis was also similar in the test–retest for all frequencies analyzed.Conclusionp13 and n23 latencies and amplitudes of VEMP for tone-burst stimuli at frequencies of 250, 500, and 1000 Hz are reproducible.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

人胚雪旺细胞组织工程神经修复坐骨神经缺损的实验研究

目的：探索人胚雪旺细胞作为组织工程的种子细胞修复周围神经缺损的可行性。方法：通过组织工程方法用PLGA导管和polyglactin 910纤维负载人胚雪旺细胞预先构置好人工神经，然后用于修复大鼠20mm的坐骨神经缺损，并与神经切断后原位缝合以及用单纯的PLGA导管进行修复的实验组进行对照。通过活体肢体功能观察、靶器官肌肉测量、电生理检测、辣根过氧化物酶示踪、连续组织切片图像分析以及透射电镜等检查神经再生情况。结果：人工神经修复组神经再生良好，效果接近于神经原位缝合组，明显优于单纯的PLGA导管修复组。结论：人胚雪旺细胞构建的人工神经可以修复20mm的周围神经缺损。     

Neu–Laxova syndrome: a case report and review of the literature

Neu-Laxova syndrome (NLS) is a rare autosomal recessive syndrome, characterized by severe intrauterine growth retardation (IUGR), microcephaly, abnormal brain development, oedema and ichthyosis. It was first reported in 1971 by Neu et al. (Pediatrics 47: 610-612) and since then no more than 60 cases have been reported. A newborn girl delivered from a 29-year-old healthy mother was admitted to hospital with a thick membrane covering her body and dismorphic appearance. The diagnosis of NLS was made according to characteristic features. The syndrome is known to have a poor prognosis and the baby lived for 9 weeks. This case is one of the longest living cases of NLS and the fourth case reported from Turkey.     

Sciatic Neuropathy: Case Report and Discussion of the Literature on Postoperative Sciatic Neuropathy and Sciatic Nerve Tumors

Sciatic nerve injury and dysfunction is not an uncommon cause of lower extremity symptoms in a musculoskeletal practice. We present the case of a man who presented with lower extremity weakness, pain, and cramps, and was initially diagnosed at an outside institution with bilateral S1 radiculopathies and recommended for spine surgery. He came to us for a second opinion. Electrodiagnostic testing revealed an isolated sciatic neuropathy and the patient was referred for imaging, which showed a sciatic nerve sheath tumor. Review of the literature on sciatic neuropathies shows that there can be many possible etiologies of sciatic nerve dysfunction, but that hip arthroplasty continues to be the leading risk factor. Sciatic nerve tumors are not commonly described in the literature and their definitive management remains unclear.