Mortality Risk factors and SOX2 and mTOR expression in Patients with Esophageal Cancer.

Causes of mortality in EC patients are not confined to cancer-specific mortality but include various protein expressions of SOX2 and mTOR in Esophageal Cancer patients and their correlation with the clinical stage. Data about the risk factors and involvement of cancer-specific protein are still lacking. This study aimed to define the risk factors and association of SOX2 and mTOR expression in mortality in patients with EC. We conducted a retrospective cohort study to assess the risk factors for cancer-specific mortality and cardiovascular mortality in patients with esophageal cancer (EC). The expression rates of SOX2, as well as MTO, were checked in patients. The multivariate analysis revealed a high-risk EC mortality with age ≥ 65 years, black race, grade, stage, and sequence of treatment; radiation after surgery; radiation before and after surgery; Surgery both before and after radiation. While the cardiovascular mortality increased with age ≥ 65 years, adenocarcinoma type, grade, stage, and sequence of treatment. The expression rates of SOX2, as well as mTOR, were 75.5 percent and 86.8 percent in Esophageal Cancer, while were 10.7 percent and 7.5 percent in osteochondroma, respectively, which was statistically significant (P<0.05). Risk factors for cancer-specific mortality and cardiovascular mortality in EC patients include older age at diagnosis, male sex, non-married status, grade III of the tumor, the regional or distant spread of the tumor, no cancer-directed therapy. The expression levels of SOX2, mTOR, and the total survival time were related to the different stages. It shows an upward trend for the expression levels of mTOR and SOX2 in Esophageal Cancer tissues. The expression levels of SOX2 and mTOR are related to the clinical stage, metastasis, and prognosis.

Regulation of Cued Fear Expression via Corticotropin-Releasing-Factor Neurons in the Ventral Anteromedial Thalamic Nucleus / 神经科学通报·英文版

The ventral part of the anteromedial thalamic nucleus (AMv) is in a position to convey information to the cortico-hippocampal-amygdalar circuit involved in the processing of fear memory. Corticotropin-releasing-factor (CRF) neurons are closely associated with the regulation of stress and fear. However, few studies have focused on the role of thalamic CRF neurons in fear memory. In the present study, using a conditioned fear paradigm in CRF transgenic mice, we found that the c-Fos protein in the AMv CRF neurons was significantly increased after cued fear expression. Chemogenetic activation of AMv CRF neurons enhanced cued fear expression, whereas inhibition had the opposite effect on the cued fear response. Moreover, chemogenetic manipulation of AMv CRF neurons did not affect fear acquisition or contextual fear expression. In addition, anterograde tracing of projections revealed that AMv CRF neurons project to wide areas of the cerebral cortex and the limbic system. These results uncover a critical role of AMv CRF neurons in the regulation of conditioned fear memory.

The evaluation and research process of cognitive impairment after aneurysmal Subarachnoid Hemorrhage / 医学研究生学报

Rupture of an intracranial aneurysm causes subarachnoid hemorrhage (SAH) occuring with a frequency of six to eight per 100 000, and has high morbidity and mortality. Cognitive dysfunction is the most common neurologic impairment after subarachnoid hemorrhage (SAH). Neuropsychological testing has been used to detect subtle cognitive impairment after SAH. However, the specific tests used often vary, and a test battery generates multiple scores that difficult to summarize and interpret. Also, detailed neuropsychological testing is invaluable for characterizing the extent and nuances of cognitive impairment in individuals. This article reviews the evaluation of cognitive impairment to further explore the mechanism and treatment.

Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways (AU)

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Mice lacking myotubularin-related protein 14 show accelerated high-fat diet-induced lipid accumulation and inflammation.

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1ß, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.

In vitro observation of haemolymph melanization and melanin-related biosynthesis enzyme genes in silkworm, Bombyx mori / 生物工程学报

The observation statistics suggested that the haemolymph melanization speed of larvae became fast and the growth inhibition of Escherichia coli was strong as the quantities of feeding on mulberry leaves increased. The RT-PCR result showed that the mRNA expressions of melanin biosynthesis enzyme BmTan, BmPo-1, BmYellow-f and BmDdc were high in the haemolyph of 5 L 3 d larvae. The qPCR analysis showed Bmtan, Bmddc, Bmyellow, Bmebony and Bmblack, especially Bmddc expression were significantly higher in black disease larvae than in normal larvae. Compared with control, Ddc inhibitors drastically inhibited the lipopolysaccharide-induced haemolymph melanization. In addition, the content of Dopa and Dopamine markedly rose after E. coli injection. These indicated that haemolymph melanization was linked to immune defenses and Bmddc may play a role in melanization response of haemolymph immune in silkworm.

PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma.

The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/ß-catenin signaling, is well known to play critical role during normal embryonic development. However, the possible involvement of PITX2 in human tumorigenesis remains unclear. In this study, we extend its function in human esophageal squamous cell carcinoma (ESCC). The real-time PCR, Western blotting and immunohistochemistry (IHC) methods were applied to examine expression pattern of PITX2 in two different cohorts of ESCC cases treated with definitive chemoradiotherapy (CRT). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point for PITX2 high expression in the training cohort. The ROC-derived cutoff point was then subjected to analyze the association of PITX2 expression with patients' survival and clinical characteristics in training and validation cohort, respectively. The expression level of PITX2 was significantly higher in ESCCs than that in normal esophageal mucosa. There was a positive correlation between PITX2 expression and clinical aggressiveness of ESCC. Importantly, high expression of PITX2 was observed more frequently in CRT resistant group than that in CRT effective group (p < 0.05). Furthermore, high expression of PITX2 was associated with poor disease-specific survival (p < 0.05) in ESCC. Then, the MTS, clonogenic survival fraction and cell apoptosis experiments showed that knockdown of PITX2 substantially increased ESCC cells sensitivity to ionizing radiation (IR) or cisplatin in vitro. Thus, the expression of PITX2, as detected by IHC, may be a useful tool for predicting CRT resistance and serves as an independent molecular marker for poor prognosis of ESCC patients treated with definite CRT.

Value of (18)F-FDG PET/CT in the diagnosis of laryngeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the clinical value of (18)F-FDGPET/CT in the diagnosis of larynx carcinoma. Methods Forty-seven patients with larynx carcinoma or suspected larynx carcinoma underwent (18)F-FDG PET/CT examination within a week before therapy. The value of (18)F-FDG PET/CT in the diagnosis and staging of the malignancy was compared with that of unenhanced contrast CT.</p><p><b>METHODS</b>Forty-seven patients with larynx carcinoma or suspected larynx carcinoma underwent (18)F-FDG PET/CT examination within a week before therapy. The value of (18)F-FDG PET/CT in the diagnosis and staging of the malignancy was compared with that of unenhanced contrast CT.</p><p><b>RESULTS</b>Among the 47 patients, a definite diagnosis of larynx carcinomas was established pathologically in 43 patients. For detection of primary tumors, the sensitivity, specificity and accuracy of (18)F-FDG PET/CT were 95.3%, 75% and 93.6%, as compared with 74.4%, 50%, and 72.3% with unenhanced contrast CT scan, respectively, showing significant differences in the diagnostic sensitivity and accuracy between the two modalities (Χ=7.340, P=0.007; Χ=7.532, P=0.006). Twenty-six of the 43 patients were identified to have lymph node metastasis, for which (18)F-FDG PET/CT showed a significantly higher diagnostic sensitivity than unenhanced contrast CT (92.3% vs 61.5%, Χ=6.933, P=0.008). In the 46 excised lymph nodes from 19 patients, 26 were found positive for metastasis, for which (18)F-FDG PET/CT showed a diagnostic sensitivity of 92%, significant higher than that with unenhanced contrast CT (64%, Χ=5.71, P=0.017). PET/CT detected synchronous tumor in one case. (18)F-FDG PET/CT resulted in a change of staging in 34.9% of the patients, including upstaging in 14 patients and down-staging in one patient.</p><p><b>CONCLUSION</b>(18)F-FDG PET/CT can be an important means for diagnosis and initial staging of larynx carcinoma.</p>

Intervention therapy of chemoradiotherapy-induced oral mucositis / 国际肿瘤学杂志

Oral mucositis is a common and serious complication secondary to chemo-radiotherapy for head and neck cancer that has a high morbidity and affects the treatment outcomes. Currently available interven-tions such as three-dimensional conformal radiotherapy and intensity-modulated radiation therapy are directed at minimizing local radiation exposure and providing symptomatic relief. Recently, a number of new treatment mo-dalities have been expected to be introduced for reduction of severity and duration of mucositis, such as kerati-nocyto growth factor, amifostine, zinc sulfate,anti-inflammation agents,glutamine,etc. These efforts are likely to improve the life quality of cancer patients significantly.