Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD).</p><p><b>METHODS</b>The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition.</p><p><b>RESULTS</b>Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis.</p><p><b>CONCLUSIONS</b>Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.</p>

Double electrodes simultaneous stimulation and implantation technique in deep brain stimulation / 中华创伤杂志(英文版)

Posttraumatic tremor is often one of the causes of disability in head injury patients. Usually, pharmacotherapy for this type of tremor is not effective. Since early 1970s, surgical ablation of the ventral thalamus has been used to treat various types of tremor. Nowadays, deep brain stimulation (DBS) confirms its efficacy in alleviating different forms of tremor, including posttraumatic tremor. Such therapy has been reported achieving around 80% success rate in the treatment of posttraumatic tremor. These successful results suggest that the application of DBS therapy can be considered as one of the alternative treatments for minimizing the tremor occurring from different pathologies.

Loss of heterozygosity on chromosome 22 in sporadic schwannoma and its relation to the proliferation of tumor cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and ultrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation.</p><p><b>METHODS</b>In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test.</p><p><b>RESULTS</b>Twenty-three schwannomas (42.6%, 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma (chi2 = 5.14, P < 0.05). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67 = 2.97, P = 0.0045; tPCNA = 2.93, P = 0.0051).</p><p><b>CONCLUSIONS</b>LOH on chromosome 22 is a frequent event in the tumorigenesis of sporadic schwannoma. And, there is a correlation between LOH on chromosome 22 and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from that in spinal schwannoma.</p>

Immunohistochemical study in dural arteriovenous fistula and possible role of ephrin-B2 for development of dural arteriovenous fistula / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although there were several clinical and experimental studies discussing the pathogenesis of dural arteriovenous fistula (DAVF), the pathological process leading to intracranial DAVF so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors for the development of DAVF and to study the biological activity of this uncommon lesion.</p><p><b>METHODS</b>We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from 6 patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors Flk-1 and Flt-1, ephrin-B2, MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques.</p><p><b>RESULTS</b>A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/6 cases. VEGF stained positive in all of the available specimens (6/6). Flk-1 showed a positive immunoreaction in only 2/6 cases and Flt-1 in 4/6 cases. Ephrin-B2 was expressed in the majority (5/6) of the cases.</p><p><b>CONCLUSIONS</b>These results support the hypothesis that DAVFs might be acquired dynamic vascular malformations with low biological activity. Vascular growth factors like VEGF and ephrin-B2 might play a pivotal role in the formation of DAVF.</p>

Relationship of survival rate, hematoma thickness and midline shift in patients with acute subdural hematomas / 中华外科杂志

<p><b>OBJECTIVE</b>To estimate outcomes of patients with acute subdural hematomas by analysing the hematoma thickness, midline shift and the differences between them.</p><p><b>METHODS</b>Ninety-five patients with acute subdural hematoma were retrospectively studied by calculating hematoma thickness, midline shift and their difference with a statistical analysis of Kaplan-Meier, Wilcoxon-Mann-Whitney U test.</p><p><b>RESULTS</b>The hematoma thickness ranged from 5.0 to 40.0 mm and midline shift was from 0 to 35.0 mm. Among these patients, 51% died and 49% survived after surgery. 18 patients (19%) showed good or satisfactory results. Kaplan-Meier analysis proved that the survival for patients with hematoma thickness approximately equal to l7 mm and a midline shift 15 mm or whose midline shift exceeded hematoma thickness by 2.2 mm, the survival rate was 50%. Glasgow outcome scale scores were correlated significantly with these parameters.</p><p><b>CONCLUSION</b>The hematoma thickness, midline shift and their difference provided a database from which criteria could be derived, that is crucial for prognosis estimation.</p>