ABSTRACT Introduction: According to the American Heart Association guideline for coronary artery bypass grafting (CABG), female patients undergoing on-pump CABG (ONCAB) are at higher risk of short-term adverse outcomes than male patients. However, whether off-pump CABG (OPCAB) can improve the short-term outcome of female patients compared to ONCAB remains unclear. Methods: We conducted a meta-analysis to study the effect of the female sex on short-term outcomes of OPCAB vs. ONCAB. A total of 31,115 patients were enrolled in 12 studies, including 20,245 females who underwent ONCAB and 10,910 females who underwent OPCAB. Results: The in-hospital mortality in female patients who underwent OPCAB was significantly lower than in those in the ONCAB group with (2.7% vs. 3.4%; odds ratio [OR] 0.76; 95% confidence interval [CI] 0.65-0.89) and without (OR 0.68; 95% CI 0.52-0.89) adjustment for cardiovascular risk factor. The incidence of postoperative stroke in female patients who underwent OPCAB was lower than in those in the ONCAB group (1.2% vs. 2.1%; OR 0.59; 95% CI 0.48-0.73) before cardiovascular risk factor adjustment but was not significant (OR 0.87; 95% CI 0,66-1.16) after adjustment. There was no significant difference in the incidence of postoperative myocardial infarction between women who underwent OPCAB and those in the ONCAB group (1.3% vs. 2.3%; OR 0.88; 95% CI 0.54-1.43). Conclusion: In contrast to the American Heart Association CABG guideline, female patients who had OPCAB don’t have unfavorable outcomes compared with the ONCAB group.

This work presented a new PEG modified calix[4]arene stationary phase (C4A-PEG-2PTSC) for gas chromatographic (GC) separations. The statically coated C4A-PEG-2PTSC column exhibited moderate polarity and column efficiency of 2224 plates m-1 determined by 1-octanol at 120 oC. The results showed that the C4A-PEG-2PTSC column exhibited the good separation performance for various types of analytes containing halogenated benzenes, benzaldehydes, phenols, alcohols, anilines isomers and showed the different retention behavior with the comparative columns. Importantly, it showed the better separation capacity of toluidine and xylidine isomers than commercial HP-35 column. Moreover, it was applied in practical sample analysis to detect the content of isomer impurities. This work exhibited the good application potential of C4A-PEG-2PTSC stationary phase in GC analyses.

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and β4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and β4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and β4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes’ α5 and β4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes’ α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed β4. Psoriatic keratinocytes’ α5 was increased by IL-13/17A, decreased by IFN-γ; but β4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and β4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently.

ABSTRACT Due to large-scale wetland reclamation, the typical wetland had been conversed to different wetland use types (upland field, paddy field, and artificial forest) in the Sanjiang Plain. However, there are scarce data regarding soil aggregates and active organic carbons during land-use transition. Here, soil aggregates and the changes in content and storage of active organic carbon [total organic carbon (TOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC), and readily oxidized carbon (ROC)] were studied under three land-uses reclaiming wetlands as an upland field, paddy field, and artificial forest in Heilongjiang Province, China. The results showed that soil aggregate structure changed significantly under the three land-uses, of which the largest decrease of mean weight diameter (MWD) occurred in the upland field. Under the three land-use types, the content and storage of TOC and each active organic carbon in soil aggregates with different size fractions significantly decreased compared with that in the wetland. In addition, the proportion of the 1–2 mm soil aggregate was significantly lower than that of other particle sizes, which resulted in the lowest storage of TOC and active organic carbon at 1-2 mm and was found in the wetland, and different land-use types; small aggregates (<0.25 mm) with a small proportion were ignored in calculating organic carbon content and storage. The TOC and active organic carbon content in various soil aggregates varied significantly in different land-use types; the paddy field was most similar to the wetland because of seasonal flooding factors. In soil aggregates with various size fractions, the paddy field presented small changes in the TOC, DOC, and MBC content, and the ROC content was significantly lower than that in the upland field and the artificial forest land-use types. The TOC, DOC, and MBC content in the upland field and the artificial forest were significantly reduced compared with that in the paddy field due to the decrease of water content in the soil. In the artificial forest, which had less human disturbance, organic carbon content was less affected than in long-term cultivated upland fields due to its abundant plant root systems and large input of organic matter. The upland field could seriously affect the structure of soil aggregates and organic carbon in the wetlands and had the most negative impact on the wetland ecosystem.

Abstract Proteomics is a powerful tool to understand molecular connections between meat proteins and quality traits. In order to research the total proteome difference and molecular mechanisms related to quality traits in different parts of yak meat. This study was designed to investigate the differences in the proteomes of yak different muscles. In this paper, Tandem Mass Tags (TMT) coupled Liquid chromatography-tandem mass spectrometry (LC-MS/MS) to study the variations of proteome in different parts of yak after it is slaughtered. In total, 88 differentially expressed proteins (DEPs) were identified among striplon (WJR), slivsid (HGT) and chuck (JR). The quality analysis of DEPs showed heat shock proteins (HSPs) and structural proteins could be used as tenderness marker proteins for different parts of yak meat. Myosin and troponin-T may be flavour marker protein in yak meat. The bioinformatics analysis revealed that DEPs are involved in glycolysis, protein structure and phosphorylation. PPI analysis revealed thatmyosin, HSPs and metabolic enzymes may have the potential to be biological markers. This study highlights that the DEPs were responsible for meat quality different.

Abstract In order to study the tenderness mechanism of difference in different parts of Yak meat, the differentially expressed proteins (DEPs) and its correlation with quality of Yak meat were studied by TMT (Tandem Mass Tags, TMT) quantitative proteomic method. The results showed that 25, 40 and 34 DEPs were identified in JR/HGT, WJR/HGT and WJR/JR groups, respectively. Correlation analysis between DEPs and quality traits of yak meat showed that there were 12 DEPs with significant correlation were correlated closely with quality traits.The relative contents of the 11 DEPs were significantly different in different parts (p < 0.05).There are 8, 9 and 6 key DEPs in JR/HGT, WJR/HGT and WJR/JR groups, respectively.The expression of these DEPs were down-regulated and up-regulated in different parts, and was closely related to the cell growth and death, carbohydrate metabolism, amino acid metabolism, protein binding, motility activity and unfolded protein binding.The significant difference of the expression of these key proteins in different parts is the internal reason of the difference of quality traits among WJR, JR and HGT.This provide a reference for the study on the mechanism of difference in Yak meat.

Abstract To investigate the function and mechanism of GINS complex subunit 2 (GINS2) in osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head (SINFH). Clinical specimens were collected from 40 cases of SINFH patients and 40 cases of control patients. Then, SINFH mouse model was built. Immediately, osteoblasts and osteoclasts were induced and differented from the pre-osteoblast cell line MC3T3-E1 and the mononuclear macrophage cell line RAW264.7 of mice, respectively. The qRT-PCR assay was used for detecting the expressions of GINS2, p53 and growth arrest and DNA damage 45A (GADD45A). The cytoactive, proliferation and apoptosis of osteoblasts and osteoclasts of SINFH mice were measured by tartaric acid phosphatase staining, CCK-8 and Annexin V-FITC/PI dual staining, respectively. GINS2 was up-regulated while p53/GADD45A was down-regulated in femoral tissues in SINFH patients and mice. GINS2 was down-regulated while p53 and GADD45A were up-regulated in osteoblasts of SINFH mice, which presented opposite trends in osteoclasts formations. GINS2 decreased osteoblasts activities and increased osteoclasts activities, inhibited apoptosis and promoted proliferation in osteoblasts and osteoclasts via p53/GADD45A pathway. GINS2 affects activity/differentiation, apoptosis and proliferation of osteoblast and osteoclast in steroid-induced osteonecrosis of the femoral head by regulating p53/GADD45A signaling pathway.

Abstract Background This paper aims to assess the impact of antibiotic therapy management by clinical pharmacists on rational drug use (RDU) in the perioperative period of patients receiving retinal detachment surgery in China from the perspective of prescription structure. Methods: In this study, a retrospective study was used to compare the differences in the RDU between 233 patients (the experimental group) receiving medical treatment and 210 patients (the control group) without clinical pharmacist intervention. The data were collected with a set of indicators adjusted from the core medication use indicator proposed by the World Health Organization and the International Network of Rational Use of Drugs according to the background of China. Results: There were significant differences in average number of drugs per prescription (19.7 and 20.8, P = 0.001), percentage of drugs on the reimbursable list (98.32% and 72.4%, P = 0.003), and average treatment expenditure per prescription (555.3 yuan and 707 yuan) between the experimental group and the controlled group, while average number of antibiotics per prescription (4.2 and 4.3, P = 0.114), average number of injections per prescription (12.02 to 11.96, P = 0.804) were not changed significantly. Conclusions: More efforts are needed to improve the effectiveness of the antibiotic therapy management by clinical pharmacist on rational drug use, meanwhile the objective of cost-saving should be included in the service pattern of clinical pharmacy services.

RESUMO Objetivo: O VEGF-D é um potencial biomarcador para linfangioleiomiomatose (LAM); entretanto, seu desempenho diagnóstico ainda não foi sistematicamente estudado. Métodos: Foram realizadas buscas nos bancos de dados PubMed, EMBASE, Scopus, Web of Science e Cochrane Library para identificar estudos primários sobre o VEGF-D com relação ao diagnóstico de LAM. A qualidade dos estudos foi avaliada por meio da ferramenta Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). As estimativas sumárias de acurácia diagnóstica foram combinadas utilizando um modelo bivariado de efeitos aleatórios. Análises de subgrupo e de sensibilidade foram realizadas para explorar possíveis heterogeneidades. O sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE) foi aplicado para avaliar a qualidade das evidências e indicar a força das recomendações. Resultados: Dez estudos envolvendo 945 pacientes eram de alto risco em qualidade, segundo a ferramenta QUADAS-2. Os parâmetros diagnósticos combinados foram indicados da seguinte forma: sensibilidade = 0,82 (IC95%: 0,71-0,90); especificidade = 0,98 (IC95%: 0,94-0,99); e OR diagnóstica = 197 (IC95%: 66-587). A ASC da análise summary ROC foi de 0,98. As análises de subgrupo e de sensibilidade revelaram que o desempenho global não foi substancialmente afetado pela composição do grupo controle, valor de corte pré-especificado, país de origem ou diferentes valores de corte (p > 0,05 para todos). Uma forte recomendação para a dosagem de VEGF-D sérico para auxiliar no diagnóstico de LAM foi feita de acordo com o sistema GRADE. Conclusões: O VEGF-D parece ter grandes implicações potenciais para o diagnóstico de LAM na prática clínica em virtude da excelente especificidade e sensibilidade subótima.

ABSTRACT Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.

Abstract Objective: To modify the chronic atrial fibrillation of atrial tachycardia pacing in beagles with a homemade pacemaker placed outside the body and to evaluate connective tissue growth factor and fibrosis of atrial tissue in our modified atrial tachycardia pacing beagle model. Methods: Twelve adult beagles of either sex were randomly divided into an atrial tachycardia pacing group and a control group (n=6 in each group). We performed the temporary pacemaker implantation at the right atrial appendage and put the pacemaker into the pocket of dog clothing in the atrial tachycardia pacing group. After eight weeks of atrial tachycardia pacing, the electrocardiography, transthoracic echocardiography, hematoxylin-eosin staining, and Masson’s staining of the right atrial appendages were performed along with the immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot analysis of connective tissue growth factor, collagen I, and collagen III. Results: In the atrial tachycardia pacing group, atrial fibrillation was induced in five beagles (83.3%); the left atrium enlarged significantly; more canines had mitral regurgitation; and the Masson’s staining, quantitative real-time polymerase chain reaction, and Western blot results demonstrated more obvious fibrosis of the left atrium. Conclusion: The modified beagle model of atrial fibrillation using a right atrium pacemaker outside the body was effective, increased connective tissue growth factor and collagen I messenger ribonucleic acid overexpression, and induced atrial fibrosis.

Resumo Introdução: Perda auditiva induzida por ruído é uma das principais doenças ocupacionais causadas pela interação gene-ambiente. O Grainy Like 2, ou GRHL2 é um gene que tem sido considerado como candidato. Nesse sentido, muitos estudos avaliaram a associação entre o GRHL2 e perda auditiva induzida por ruído, embora os resultados sejam ambíguos e conflitantes. Objetivo: Identificar uma estimativa precisa da associação entre o polimorfismo rs3735715 no gene GRHL2 e a suscetibilidade à perda auditiva induzida por ruído. Método: Uma pesquisa abrangente foi feita para coletar dados até 8 de julho de 2018. No fim, quatro artigos elegíveis foram incluídos nesta metanálise, abrangeram 2.410 indivíduos. As odds ratios agrupadas com intervalos de confiança de 95% foram usadas para avaliar a força da associação. Resultados: Uma associação significante foi encontrada na população geral no modelo de dominância (GA/AA vs. GG, odds ratio = 0,707, intervalo de confiança 95% = 0,594-0,841) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,189, intervalo de confiança 95% = 1,062 a 1,333). Quando estratificados pelo local de trabalho dos indivíduos, também encontramos associação entre rs3735715 e risco de perda auditiva induzida por ruído no modelo de dominância (GA/AA vs. GG, odds ratio = 0,634, intervalo de confiança 95% = 0,514 ± 0,783) e modelo de alelo (alelo G vs. alelo A; odds ratio = 1,206, intervalo de confiança 95% = 1,054- 1,379). Conclusão: O polimorfismo Rs3735715 no gene GRHL2 pode influenciar a suscetibilidade à perda auditiva induzida por ruído. Estudos adicionais, amplos, bem desenhados e funcionais são necessários para confirmar essa associação em diferentes populações.

Abstract Instruction: Noise-induced hearing loss is a leading occupational disease caused by gene-environment interaction. The Grainy Like 2, GRHL2, is a candidate gene. In this regard, many studies have evaluated the association between GRHL2 and noise-induced hearing loss, although the results are ambiguous and conflicting. Objective: The purpose of this study was to identify a precise estimation of the association between rs3735715 polymorphism in GRHL2 gene and susceptibility of noise-induced hearing loss. Methods: A comprehensive search was performed to collect data up to July 8, 2018. Finally, 4 eligible articles were included in this meta-analysis comprising 2410 subjects. The pooled odds ratios with 95% confidence intervals were used to evaluate the strength of the association. Results: Significant association was found in the overall population in the dominant model (GA/AA vs. GG, odds ratio = 0.707, 95% confidence interval = 0.594-0.841) and allele model (G allele vs. A allele, odds ratio = 1.189, 95% confidence interval = 1.062-1.333). When stratified by source of the subjects, we also found association between rs3735715 and noise-induced hearing loss risk in the dominant model (GA/AA vs. GG, odds ratio = 0.634, 95% confidence interval = 0.514-0.783) and allele model (G allele vs. A allele, odds ratio = 1.206, 95% confidence interval = 1.054-1.379). Conclusion: Rs3735715 polymorphism in GRHL2 gene may influence the susceptibility of noise-induced hearing loss. Additional large, well-designed and functional studies are needed to confirm this association in different populations.

Resumen La válvula de energía nuclear es un equipo importante en cualquier sistema de energía nuclear. El método de elementos finitos se utilizó en este estudio para analizar la resistencia y la rigidez de la válvula de compuerta nuclear de alta temperatura y alta presión. Las características estructurales se optimizaron según los parámetros que afectan la resistencia del cuerpo de la válvula. La tecnología de acoplamiento fluido-sólido se utilizó para investigar la temperatura, la deformación y las distribuciones de tensiones en la estructura. Se observó una alta concentración de tensiones en el diseño inicial; El esfuerzo equivalente máximo excedió el rango permitido. Se desplegaron tres métodos de optimización en un esfuerzo por mejorar la distribución del estrés. Se encontró que la distribución de la tensión era más uniforme después de la optimización y la estructura de la válvula de compuerta de los tres esquemas probados cumplía con los requisitos de tensión relevantes. El esquema óptimo se determinó luego mediante una comparación adicional. Los resultados presentados aquí pueden proporcionar una referencia teórica para la optimización de los diseños de válvulas de energía nuclear.

Abstract The nuclear power valve is an important piece of equipment in any nuclear power system. The finite element method was used in this study to analyze the strength and rigidity of the high-temperature and high-pressure nuclear gate valve. The structural characteristics were optimized as per the parameters that affect the strength of the valve body. Fluid-solid coupling technology was utilized to investigate the temperature, deformation, and stress distributions in the structure. A high stress concentration was observed in the initial design; the maximum equivalent stress exceeded the allowable range. Three optimization methods were deployed in efforts to improve the stress distribution. The stress distribution was found to be more uniform post-optimization and the gate valve structure of all three schemes tested met the relevant stress requirements. The optimal scheme was then determined by further comparison. The results presented here may provide a theoretical reference for the optimization of nuclear power valve designs.

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.

Resumo Introdução: A quinase 3 sérica induzida por glicocorticoide, uma serina/treonina quinase que funciona downstream da via de sinalização PI3K, desempenha um papel crítico nos processos neoplásicos. É expressa por vários tumores e contribui para a carcinogênese. Objetivo: Investigar a expressão de quinase 3 sérica induzida por glicocorticoide no carcinoma nasofaríngeo, estudar os efeitos antitumorais do shRNA da quinase 3 sérica induzida por glicocorticoide, que inibem sua expressão em células de carcinoma nasofaríngeo, e discutir as implicações potenciais de nossos achados. Método: A expressão de proteína quinase 3 sérica induzida por glicocorticoide em linhagens de células de carcinoma nasofaríngeo (CNE-1, CNE-2, HNE-1, HONE-1 e SUNE-1) e a linhagem de células humanas imortalizadas do epitélio nasofaríngeo NP69 foram avaliadas por Western blot. A expressão da quinase 3 sérica induzida por glicocorticoide em 42 tecidos de CNF embebidos em parafina foi feita por imuno-histoquímica. Testes com MTT, citometria de fluxo e testes de raspagem foram feitos após as células CNE-2 terem sido transfectadas com o melhor plasmídeo shRNA da quinase 3 sérica induzida por glicocorticoide selecionado por Western blot, com o uso de lipofectamina para estudar seu efeito na proliferação, apoptose e migração celular. Resultados: Foi observada uma sobre-expressão da quinase 3 sérica induzida por glicocorticoide em tecidos e células de carcinoma nasofaríngeo humanas. A expressão de quinase 3 sérica induzida por glicocorticoide diminuiu acentuadamente após as células CNE-2 terem sido transfectadas com o shRNA da quinase 3 sérica induzida por glicocorticoide, conduzindo a forte inibição de proliferação e migração celular. Além disso, a taxa de apoptose aumentou nas células CNE-2 após o knockdown da quinase 3 sérica induzida por glicocorticoide. Conclusão: A expressão de quinase 3 sérica induzida por glicocorticoide foi observada com maior frequência à medida que o epitélio nasofaríngeo progride de tecido normal para carcinoma. Isso sugere que a quinase 3 sérica induzida por glicocorticoide contribui para o processo multietapas da carcinogênese do carcinoma nasofaríngeo. A quinase 3 sérica induzida por glicocorticoide representa um alvo para a terapia do carcinoma nasofaríngeo e há uma base para a investigação adicional dessa modalidade de tratamento adjuvante para o carcinoma nasofaríngeo.

Abstract Introduction: Serum- and glucocorticoid-inducible kinase 3, a serine/threonine kinase that functions downstream of the PI3K signaling pathway, plays a critical role in neoplastic processes. It is expressed by various tumors and contributes to carcinogenesis. Objective: The objective was to investigate serum- and glucocorticoid-inducible kinase 3 expression in nasopharyngeal carcinoma, to study the anti-tumor effects of serum- and glucocorticoid-inducible kinase 3 shRNA by inhibiting its expression in nasopharyngeal carcinoma cells and to discuss the potential implications of our findings. Methods: Serum- and glucocorticoid-inducible kinase 3 protein expression in nasopharyngeal carcinoma cell lines (CNE-1, CNE-2, HNE-1, HONE-1, and SUNE-1) and the human immortalized nasopharyngeal epithelium cell line NP69 were assayed by western blotting. Serum- and glucocorticoid-inducible kinase 3 expression in 42 paraffin-embedded nasopharyngeal carcinoma tissues were performed by immunohistochemistry. MTT assay, flow cytometry, and scratch tests were performed after CNE-2 cells were transfected with the best serum- and glucocorticoid-inducible kinase 3 shRNA plasmid selected by western blotting using lipofectamine to study its effect on cell proliferation, apoptosis, and migration. Results: Serum- and glucocorticoid-inducible kinase 3 was overexpressed in human nasopharyngeal carcinoma tissues and cells. Serum- and glucocorticoid-inducible kinase 3 expression decreased markedly after CNE-2 cells were transfected with the serum- and glucocorticoid-inducible kinase 3 shRNA, leading to strong inhibition of cell proliferation and migration. In addition, the apoptosis rate increased in CNE-2 cells after serum- and glucocorticoid-inducible kinase 3 knockdown. Conclusion: Serum- and glucocorticoid-inducible kinase 3 expression was more frequently observed as the nasopharyngeal epithelium progresses from normal tissue to carcinoma. This suggests that serum- and glucocorticoid-inducible kinase 3 contributes to the multistep process of NPC carcinogenesis. Serum- and glucocorticoid-inducible kinase 3 represents a target for nasopharyngeal carcinoma therapy, and a basis exists for the further investigation of this adjuvant treatment modality for nasopharyngeal carcinoma.