Rac1和Cdc42在乳腺癌中的表达和临床意义

目的:研究Rac1和Cdc42在人乳腺癌中的表达及临床意义。方法:收集339例人乳腺癌组织样本,通过免疫组化的方法检测Rac1和Cdc42的表达情况,并分析其与乳腺癌临床病理学特征间的相关性。结果:Rac1和Cdc42在正常乳腺组织中几乎不表达,而在肿瘤组织的阳性表达率分别为35.9%和38.5%,均较正常乳腺组织显著升高,差异均具有统计学意义(P0.001和P0.05)。卡方检验分析表明,二者的表达与患者的年龄、肿瘤大小、组织分化程度、HER2状态无关(P0.05),而与TNM分期、淋巴结转移、肿瘤侵袭、ER状态和Ki-67表达有相(P0.05)。相关性分析表明,Rac1和Cdc42的表达与高TNM分期(r分别为0.443和0.295;P均0.001)、淋巴结转移阳性(r均为0.480和0.562;P均0.001)、肿瘤侵袭(r分别为0.412和0.440;P均0.001)、ER阴性表达(r分别为-0.517和-0.342;P均0.001)以及Ki-67高表达(r分别为0.338和0.454;P均0.001)呈正相关。结论:在乳腺癌组织中,Rac1和Cdc42作为癌基因表达增加,可能在乳腺癌恶性进程中发挥重要作用。     

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid,and Strontium Levels in Adult Men According to the US 2011–2012 National Health and Nutrition Examination Survey

BackgroundLittle is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012).MethodsUrinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio.ResultsAdjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; P_trend = 0.044), 1.84 (95% CI: 1.02, 3.34; P_trend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone.ConclusionsThe National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men.     

Prediction of Perioperative Cardiac Events through Preoperative NT-pro-BNP and cTnI after Emergent Non-Cardiac Surgery in Elderly Patients

Objectives

Clinical risk stratification has an important function in preoperative evaluation of patients at risk for cardiac events prior to non-cardiac surgery. The aim of this study was to determine whether the combined measurement of pre-operative N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin I (cTnI) could provide useful prognostic information about postoperative major adverse cardiac events (MACE) within 30 days in patients aged over 60 years undergoing emergent non-cardiac surgery.

Methods

The study group comprised 2519 patients aged over 60 years that were undergoing emergent non-cardiac surgery between December 2007 and December 2013. NT-pro-BNP and cTnI were measured during hospital admission. The patients were monitored for MACE (cardiac death, non-fatal myocardial infarction, or cardiac arrest) during the 30-day postoperative follow-up period.

Results

MACE occurred in 251 patients (10.0%). Preoperative NT-pro-BNP and cTNI level were significantly higher in the individuals that experienced MACE than in those who did not (P < 0.001). The confounding factors of age, sex, co-morbidities and preoperative medications were adjusted in a multivariate logistic regression analysis. This analysis showed that preoperative NT-proBNP level > 917 pg/mL (OR 4.81, 95% CI 3.446–6.722, P < 0.001) and cTnI ≥ 0.07 ng/mL (OR 8.74, 95% CI 5.881–12.987, P < 0.001) remained significantly and independently associated with MACE after the adjustment of the confounding factors. Kaplan-Meier event-free survival curves demonstrated that patients with preoperative simultaneous NT-proBNP level > 917 pg/mL and cTnT ≥0.07 ng/mL had worse event-free survival than individual assessments of either biomarker.

Conclusion

Preoperative plasma NT-proBNP and cTnI are both independently associated with an increased risk of MACE in elderly patients after emergent non-cardiac surgery. The combination of these biomarkers provides better prognostic information than using either biomarker separately.     

Olfactory Dysfunction and Neurotransmitter Disturbance in Olfactory Bulb of Transgenic Mice Expressing Human A53T Mutant α-Synuclein

Parkinson disease is a multi-system neurodegenerative disease characterized by both motor and non-motor symptoms. Hyposmia is one of the early non-motor symptoms occurring in more than 90% of Parkinson disease cases, which can precede motor symptoms even several years. Up to now, the relationship between hyposmia and Parkinson disease remains elusive. Lack of proper animal models of hyposmia restricts the investigation. In this study we assessed olfactory function in Prp-A53T-α-synuclein transgenic (αSyn^A53T) mice which had been reported to show age-dependent motor impairments and intracytoplasmic inclusions. We also examined cholinergic and dopaminergic systems in olfactory bulb of αSyn^A53T mice by immunofluorescent staining, enzyme linked immunosorbent assay and western blot. We found that compared to wild type littermates, αSyn^A53T mice at 6 months or older displayed a deficit of odor discrimination and odor detection. No significant changes were found in olfactory memory and odor habituation. Furthermore compared to wildtype littermates, in olfactory bulb of αSyn^A53T mice at 10 months old we detected a marked decrease of cholinergic neurons in mitral cell layer and a decrease of acetylcholinesterase activity, while dopaminergic neurons were found increased in glomerular layer, accompanied with an increase of tyrosine hydroxylase protein. Our studies indicate that αSyn^A53T mice have olfactory dysfunction before motor deficits occur, and the cholinergic and dopaminergic disturbance might be responsible for the Parkinson disease-related olfactory dysfunction.     

Quality of Life Is Related to Social Support in Elderly Osteoporosis Patients in a Chinese Population

Objective

To explore the association between quality of life and social support in elderly osteoporosis patients in a Chinese population.

Methods

A total of 214 elderly patients who underwent bone mineral density screening were divided into two groups: elderly patients with primary osteoporosis (case group, n = 112) and normal elderly patients (control group, n = 102). Quality of life and social support were compared between the two groups.

Results

Quality of life and social support were significantly different between the case and control groups. The physical function, role-physical, bodily pain, general health, vitality, social-functioning, role-emotional and mental health scores in case group were significantly lower than those in the control group (P < 0.01). The objective support, subjective support, utilization of support, and total scores in case group were significantly lower than those in the control group (P < 0.01). Quality of life and social support were positively correlated in the case group (r = 0.672, P < 0.01).

Conclusion

Quality of life and social support in elderly patients with osteoporosis in China were poorer than in elderly patients without osteoporosis and were positively correlated. Our findings indicate that increased efforts to improve the social support and quality of life in elderly osteoporosis patients are urgently needed in China. Further longitudinal studies should be conducted to provide more clinical evidence to determine causative factors for the observed association between risk factors and outcomes.     

High Level Expression of a Novel Family 3 Neutral β-Xylosidase from Humicola insolens Y1 with High Tolerance to D-Xylose

A novel β-xylosidase gene of glycosyl hydrolase (GH) family 3, xyl3A, was identified from the thermophilic fungus Humicola insolens Y1, which is an innocuous and non-toxic fungus that produces a wide variety of GHs. The cDNA of xyl3A, 2334 bp in length, encodes a 777-residue polypeptide containing a putative signal peptide of 19 residues. The gene fragment without the signal peptide-coding sequence was cloned and overexpressed in Pichia pastoris GS115 at a high level of 100 mg/L in 1-L Erlenmeyer flasks without fermentation optimization. Recombinant Xyl3A showed both β-xylosidase and α-arabinfuranosidase activities, but had no hydrolysis capacity towards polysaccharides. It was optimally active at pH 6.0 and 60°C with a specific activity of 11.6 U/mg. It exhibited good stability over pH 4.0–9.0 (incubated at 37°C for 1 h) and at temperatures of 60°C and below, retaining over 80% maximum activity. The enzyme had stronger tolerance to xylose than most fungal GH3 β-xylosidases with a high K_i value of 29 mM, which makes Xyl3A more efficient to produce xylose in fermentation process. Sequential combination of Xyl3A following endoxylanase Xyn11A of the same microbial source showed significant synergistic effects on the degradation of various xylans and deconstructed xylo-oligosaccharides to xylose with high efficiency. Moreover, using pNPX as both the donor and acceptor, Xyl3A exhibited a transxylosylation activity to synthesize pNPX₂. All these favorable properties suggest that Xyl3A has good potential applications in the bioconversion of hemicelluloses to biofuels.     

Apple Fruit Diameter and Length Estimation by Using the Thermal and Sunshine Hours Approach and Its Application to the Digital Orchard Management Information System

In apple cultivation, simulation models may be used to monitor fruit size during the growth and development process to predict production levels and to optimize fruit quality. Here, Fuji apples cultivated in spindle-type systems were used as the model crop. Apple size was measured during the growing period at an interval of about 20 days after full bloom, with three weather stations being used to collect orchard temperature and solar radiation data at different sites. Furthermore, a 2-year dataset (2011 and 2012) of apple fruit size measurements were integrated according to the weather station deployment sites, in addition to the top two most important environment factors, thermal and sunshine hours, into the model. The apple fruit diameter and length were simulated using physiological development time (PDT), an indicator that combines important environment factors, such as temperature and photoperiod, as the driving variable. Compared to the model of calendar-based development time (CDT), an indicator counting the days that elapse after full bloom, we confirmed that the PDT model improved the estimation accuracy to within 0.2 cm for fruit diameter and 0.1 cm for fruit length in independent years using a similar data collection method in 2013. The PDT model was implemented to realize a web-based management information system for a digital orchard, and the digital system had been applied in Shandong Province, China since 2013. This system may be used to compute the dynamic curve of apple fruit size based on data obtained from a nearby weather station. This system may provide an important decision support for farmers using the website and short message service to optimize crop production and, hence, economic benefit.     

Tumor Necrosis Factor-α-Induced Ototoxicity in Mouse Cochlear Organotypic Culture

Tumor necrosis factor (TNF)-α is a cytokine involved in acute inflammatory phase reactions, and is the primary upstream mediator in the cochlear inflammatory response. Treatment of the organ of Corti with TNF-α can induce hair cell damage. However, the resulting morphological changes have not been systematically examined. In the present study, cochlear organotypic cultures from neonatal mice were treated with various concentrations and durations of TNF-α to induce inflammatory responses. Confocal microscopy was used to evaluate the condition of hair cells and supporting cells following immunohistochemical staining. In addition, the ultrastructure of the stereocilia bundle, hair cells, and supporting cells were examined by scanning and transmission electron microscopy. TNF-α treatment resulted in a fusion and loss of stereocilia bundles in hair cells, swelling of mitochondria, and vacuolation and degranulation of the endoplasmic reticulum. Disruption of tight junctions between hair cells and supporting cells was also observed at high concentrations. Hair cell loss was preceded by apoptosis of Deiters’ and pillar cells. Taken together, these findings detail the morphological changes in the organ of Corti after TNF-α treatment, and provide an in vitro model of inflammatory-induced ototoxicity.     

Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis

Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07) and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS) to invasive cancer (OR=3.75; 95% CI, 1.8-7.78). Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43). Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.     

Region-Oriented and Staged Treatment Strategy in Reconstruction of Severe Cervical Contracture

Introduction

Severe cervical contracture after burns causes obvious impairment of neck movement and the aesthetic silhouette. Although various surgical techniques for treatment have been described, there is not a definitive strategy to guide treatment. Over the past 6 years, we have been utilizing a region-oriented and staged treatment strategy to guide reconstruction of severe cervical contracture. Satisfactory results have been achieved with this strategy.

Methods

The first stage of treatment focuses on the anterior cervical region and submental region. Procedures include cicatrix resection, contracture release, division and elevation of the platysma to form two platysma flaps, and skin grafting. Three to six months later, the second stage treatment is performed, which localize to the mental region. This includes scar resection, correction of the lower lip eversion, and reconstruction with free (para)scapular skin flap. Three subtypes of cervicomental angle that we proposed were measured as quantitative tool for evaluation of the reconstruction.

Results

24 patients who completed the treatment were reviewed. By the 3rd postoperative month, their CM angles changed significantly: the soft tissue CM angle was reduced from 135.0° ± 17.3° to 111.1° ± 11.3°, the osseous CM angle increased from 67.1° ± 9.0° to 90.5° ± 11.6° and the dynamic CM angle increased from 21.9° ± 8.7° to 67.4° ± 13.1°. 22 in 24 (91.7%) of these patients gained notable improvement of cervical motion and aesthetic contour.

Conclusions

Our results suggest that the region-oriented and staged treatment strategy can achieve satisfactory functional and aesthetic results, combining usage of both skin graft and skin flap while minimizing the donor site morbidity.