The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Multiple correspondence analysis of the influencing factors of injury among left behind primary school students in Pingliang / 中国学校卫生

Objective@#To explore the distribution characteristics of the influencing factors of injury among left behind primary school students, so as to provide a reference for identifying high risk injury groups and carrying out accurate injury intervention.@*Methods@#From August 2021 to July 2022, a questionnaire survey was conducted among 3 769 students from grades 4 to 6 from nine primary schools in three townships in Pingliang City by using the a random cluster sampling method. Multiple correspondence analysis was used to analyze the influencing factors of injury.@*Results@#The detection rate of injuries among non left behind pupils was 21.8%(573/2 631), whereas the detection rate of injuries among left behind pupils was 40.9%(466/1 138). In addition, a statistically significant difference was observed in the detection rate of injuries between left behind pupils and non left behind pupils ( χ 2=146.21, P <0.01). Among the injuries of left behind pupils, 263 had fall related injuries, accounting for the highest proportion ( 56.4 %). Whether it was an only child，and different grades, gender, personality, psychological status, monitoring type, and maternal education level were statistically significant ( χ 2=39.05, 96.69, 143.00, 155.80, 461.39, 285.35, 17.10, P <0.01). The multiple correspondence analysis category graph showed higher rates of fall injuries, blunt injuries and sharp injuries among boys, extroverted personality types, and left behind pupils whose grandparents were their legal guardians. Animal bites, burns and other injury types were higher among left behind pupils with an introverted personality, pupils in peer/other guardianship situations, and those with a sub mental health status. Unharmed left behind students mainly included those with intermediate personality and mental health characteristics.@*Conclusion@#The injury detection rate among left behind primary school students is high. Gender, personality type, guardianship type, and mental health status are closely related to injury. Extroverted boys under grandparents guardians are identified as high risk groups for injury prevention and control. Under the guidance of the precision prevention model, precision intervention strategies for all round high risk groups should be carried out in order to effectively reduce the occurrence of injuries among left behind pupils.

Impact of posture and recovery methods on sports injuries / Impacto da postura no esporte e métodos de recuperação nas lesões esportivas / Impacto de la postura y métodos de recuperación en las lesiones deportivas

ABSTRACT Introduction Exercise methods with incorrect posture or inadequate repetitive movements may cause irreversible long-term body damage. There is a growing interest in ergonomics in martial arts, but taekwondo lacks studies. Objective Evaluate the postural ergonomics impact on injuries and rehabilitation in taekwondo athletes. Methods 13 taekwondo team members from a sports academy had their posture and injury characteristics evaluated. Research methods, experimental and mathematical statistics investigated the athletes' postural and body diagnosis, confronting the information with their injury history, pain, and injury duration. Results Nine athletes suffered injuries and pain in the pelvic girdle and ankle joints; the odds are 69.23%, pelvic girdle and ankle joints have the highest frequency of injuries, followed by knee injuries (46.15%), and foot joints (30.77%). Injuries to the thigh, wrist, and shoulder joints were detected in 23.08% of athletes. Conclusions The results of this study indicate postural dysfunctions can be corrected with motor function evaluation and early rehabilitation based on ergonomic sports posture. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução Métodos de exercício com postura incorreta ou movimentos repetitivos inadequados podem causar danos corporais irreversíveis à longo prazo. Há um crescente interesse sobre a ergonomia nas artes marciais porém o taekwondo carece de estudos. Objetivo Avaliar o impacto da ergonomia postural nas lesões e a reabilitação em atletas de taekwondo. Métodos 13 membros da equipe de taekwondo de uma academia esportiva tiveram suas posturas e características de lesão avaliadas. Usando método de pesquisa, experimental e estatística matemática, investigou-se os dados de diagnóstico postural e corporal dos esportistas confrontando as informações com o histórico de lesões, dor e tempo de lesão. Resultados Há 9 atletas que sofreram lesões e dores na cintura pélvica e articulações do tornozelo, as probabilidades são de 69,23%, as articulações da cintura pélvica e do tornozelo têm a maior frequência de lesões; seguida por lesões no joelho (46,15%), e as articulações dos pés (30,77%). Lesões nas coxas, articulações do pulso e ombros foram detectadas em 23,08% esportistas. Conclusões Os resultados deste estudo mostram que as disfunções posturais podem ser corrigidas com avaliação da função motora e a reabilitação precoce baseados na postura ergonômica do esporte. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción Los métodos de ejercicio con posturas incorrectas o movimientos repetitivos inadecuados pueden causar daños corporales irreversibles a largo plazo. Existe un creciente interés por la ergonomía en las artes marciales, pero el taekwondo carece de estudios. Objetivo Evaluar el impacto de la ergonomía postural en las lesiones y en la rehabilitación de los atletas de taekwondo. Métodos Se evaluaron las posturas y las características de las lesiones de 13 miembros del equipo de taekwondo de una academia deportiva. Utilizando el método de investigación, experimental y estadística matemática, se investigaron los datos de diagnóstico postural y corporal de los atletas, confrontando la información con su historial de lesiones, el dolor y el tiempo de lesión. Resultados Hay 9 atletas que sufrieron lesiones y dolor en las articulaciones de la cintura pélvica y el tobillo, las probabilidades son del 69,23%, las articulaciones de la cintura pélvica y el tobillo tienen la mayor frecuencia de lesiones; seguidas de las lesiones de rodilla (46,15%), y las articulaciones del pie (30,77%). Se detectaron lesiones en las articulaciones del muslo, la muñeca y el hombro en el 23,08% de los atletas. Conclusiones Los resultados de este estudio muestran que las disfunciones posturales pueden corregirse con la evaluación de la función motora y la rehabilitación temprana basada en la postura deportiva ergonómica. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Physical changes in taekwondo athletes caused by strengthening the core / Alterações físicas nos atletas de taekwondo provocadas pelo fortalecimento do core / Cambios físicos en los atletas de taekwondo causados por el fortalecimiento del core

ABSTRACT Introduction: Taekwondo is a complete sport with combative nature among related sports. Their athletes need a higher strike force in the legs and a body with relatively high sensitivity and stability. The center of force production, from which all movements originate, is called the core. Objective: The purpose of this study is to analyze possible physical changes in Taekwondo athletes caused by strengthening the core. Methods: Baseline data from core training was recorded using various scientific analysis methods. Rigorous methods of comparison were also employed. The six indices of athletic ability were tested in experimental and control groups in Taekwondo athletes. Results: The data in the athletes' strength and exercise styles before and after core strengthening showed significant differences. Conclusion: Strengthening the core of athletes can rapidly improve the development of physical strength. Core strengthening is an effective procedure for improving strength training in Taekwondo athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O Taekwondo é o esporte mais completo com natureza combativa entre os esportes relacionados. Seus atletas precisam ter maior força de ataque nas pernas e um corpo com sensibilidade e estabilidade relativamente altas. O centro de produção de força, de onde se originam todos os movimentos é chamado de core. Objetivo: O objetivo deste estudo é analisar as possíveis alterações físicas nos atletas de Taekwondo provocadas pelo fortalecimento do core. Métodos: Dados basais do treinamento no core foram registrados usando uma variedade de métodos de análise científica. Foram empregados também, rigorosos métodos de comparação. Os 6 índices de capacidade atlética foram testados em grupos experimentais e de controle nos atletas de Taekwondo. Resultados: Os dados na força dos atletas e nos estilos de exercício antes e depois do fortalecimento do core mostraram grandes diferenças. Conclusão: O fortalecimento no core dos atletas pode melhorar rapidamente o desenvolvimento da força física. O fortalecimento do core mostrou-se um procedimento eficaz de melhora no treinamento de força nos atletas de Taekwondo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El taekwondo es el deporte de naturaleza combativa más completo entre los deportes relacionados. Sus atletas necesitan tener una mayor fuerza de ataque en las piernas y un cuerpo con una sensibilidad y estabilidad relativamente altas. El centro de producción de la fuerza, desde donde se originan todos los movimientos, se llama core. Objetivo: El propósito de este estudio es analizar los posibles cambios físicos en los atletas de Taekwondo causados por el fortalecimiento del core. Métodos: Se registraron los datos de referencia del entrenamiento básico utilizando diversos métodos de análisis científico. También se emplearon métodos rigurosos de comparación. Los 6 índices de capacidad atlética se probaron en grupos experimentales y de control en atletas de Taekwondo. Resultados: Los datos en la fuerza de los atletas y en los estilos de ejercicio antes y después del fortalecimiento del core mostraron grandes diferencias. Conclusión: El fortalecimiento del core de los atletas podría mejorar rápidamente el desarrollo de la fuerza física. Se ha demostrado que el fortalecimiento del core es un procedimiento eficaz para mejorar el entrenamiento de la fuerza en los atletas de taekwondo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Research progress on the health effects of occupational noise exposure on cardiovascular system of workers / 中国职业医学

@#Noise is a common occupational hazardous factor in the workplace. In addition to the specific damage to the auditory ， system of workers it can also harm the cardiovascular system and cause a serious disease burden. The mechanism of ， occupational noise on the cardiovascular system of workers is mainly oxidative stress inflammation and vascular endothelial ， - - - damage. As a stressor noise mainly leads to the changes of sympathoadrenal medullary system and hypothalamic pituitary ， ， ， - ， adrenal axis. The substances that play an important role include catecholamines cortisol angiotensin Ⅱ endothelin 1 - endothelial nitric oxide synthase and interleukin 6. The population epidemiological studies have shown that occupational noise ， exposure can lead to elevated blood pressure abnormal electrocardiogram and elevated blood lipids in workers. The influencing （ ， ， ） factors include noise characteristics intensity cumulative noise exposure and frequency and noise combined with other （ ， ， ， - ， occupational hazards such as high temperature welding fumes organic solvents hand transmitted vibration and work ） ， ， ， shifts . However due to the influence of research conditions experimental design and other factors some research conclusions still have limitations. More prospective and comprehensive studies are needed to verify the relevant conclusions in the future.

Associação da hipertensão com a gravidade e a mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China: Estudo unicêntrico e retrospectivo / Association of hypertension with severity and mortality in hospitalized patients with COVID-19 in wuhan, China: A single-centered, retrospective study

Resumo Fundamento A doença Coronavírus 2019 (COVID-19), causada pela síndrome respiratória aguda grave Coronavírus 2 (SARS-CoV-2), espalhou-se pelo mundo. Objetivo Investigar a associação entre a hipertensão e a gravidade/mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China. Métodos Um total de 337 pacientes diagnosticados com COVID-19 no Sétimo Hospital da cidade de Wuhan, de 20 de janeiro a 25 de fevereiro de 2020, foram inseridos e analisados em um estudo de caso unicêntrico e retrospectivo. O nível de significância adotado para a análise estatística foi 0,05. Resultados Dos 337 pacientes com diagnóstico confirmado de COVID-19, 297 (87.8%) tiveram alta do hospital e 40 pacientes (22,9%) morreram. A idade média foi de 58 anos (variando de 18 a 91 anos). Havia 112 (33,2%) pacientes diagnosticados com hipertensão no momento da internação (idade média, 65,0 anos [variação, 38-91 anos]; sendo 67 homens [59,8%, IC95%: 50,6%-69,0%], p=0,0209). Pacientes com hipertensão apresentaram uma porção significativamente maior de casos graves (69 [61,6%, IC95%: 52,5%-70,8%] vs. 117 [52,0%, IC95%: 45,4%-58,6%] em pacientes graves e 23 [19,3%, IC95%: 12,9%-28,1%] vs. 27 [12,0%, IC95%: 7,7%-16,3%] em pacientes críticos, p=0,0014) e maiores taxas de mortalidade (20 [17,9%, IC95%: 10,7%-25,1%] vs. 20 [8,9%, IC95%: 5,1%-12,6%, p=0,0202). Além disso, pacientes hipertensos apresentaram níveis anormais de vários indicadores, como linfopenia e inflamação, e nas funções cardíacas, hepáticas, renais e pulmonares no momento da internação. O grupo de pacientes com hipertensão também demonstrou níveis maiores de TNT e creatinina próximo da alta. Conclusão A hipertensão está altamente associada à gravidade ou mortalidade da COVID-19. Um tratamento agressivo deve ser considerado para pacientes hipertensos com COVID-19, principalmente com relação a lesões cardíacas e dos rins.

Abstract Background Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Objective To investigate the association between hypertension and severity/mortality in hospitalized patients with COVID-19 in Wuhan, China. Methods A total of 337 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, from January 20 to February 25, 2020, were enrolled and analyzed in a retrospective, single-center case study. The significance level adopted in the statistical analysis was 0.05. Results Of the 337 patients with confirmed diagnosis of COVID-19, 297 (87.8%) were discharged from the hospital and 40 patients (22.9%) died. The median age was 58 years (range, 18-91 years). There were 112 (33.2%) patients diagnosed with hypertension at admission (median age, 65.0 years [range, 38-91 years]; 67 [59.8%, 95%CI: 50.6%-69.0%] men, p=0.0209). Patients with hypertension presented a significantly higher portion of severe cases (69 [61.6%, 95%CI:52.5%-70.8%] vs. 117 [52.0%, 95%CI: 45.4%-58.6%] in severe patients and 23 [19.3%, 95%CI:12.9%-28.1%] vs. 27 [12.0%, 95%CI: 7.7%-16.3%] in critical patients, p=0.0014) and higher mortality rates (20 [17.9%, 95%CI: 10.7%-25.1%] vs. 20 [8.9%, 95%CI: 5.1%-12.6%, p=0.0202). Moreover, hypertensive patients presented abnormal levels of multiple indicators, such as lymphopenia, inflammation, heart, liver, kidney, and lung function at admission. The hypertension group still displayed higher levels of TnT and creatinine at approaching discharge. Conclusion Hypertension is strongly associated with severity or mortality of COVID-19. Aggressive treatment may be considered for COVID-19 patients with hypertension, especially regarding cardiac and kidney injury.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study

ABSTRACT Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. Subjects and methods: This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. Results: Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. Conclusion: The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

An updated meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer

Aim of Study: There were many reports published on the relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer in these years. In previous, we conducted a meta-analysis to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer. This study was conducted to update it. Materials and Methods: The association studies were identified from PubMed and Cochrane Library on March 1, 2016. Results: Sixty-three reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 21,220 patients with lung cancer and 21,496 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations and in Asians (overall populations: Odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.07–1.28, P = 0.006; Asians: OR = 1.41, 95% CI: 1.23–1.62, P < 0.00001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population, and Africans. Conclusion: GSTT1 null genotype is associated with the lung cancer risk in overall populations and in Asians

Relationship between extracellular vesicles and radiation-induced tissue injury / 中国组织工程研究

BACKGROUND: Radiation-induced tissue injury is one of the more serious side effects of cancer patients after radiotherapy. Recent studies have shown that in the radiation-induced tissue injury model, extracellular vesicles as intercellular information carriers have two sides. On the one hand, they participate in the radiation-induced tissue injury process to mediate tissue damage. On the other hand, they participate in radiation-induced tissue injury repair by transferring biologically active substances. OBJECTIVE: To summarize the damage and repair effects of extracellular vesicles from different sources on radioactive tissue damage and to clarify the relationship between extracellular vesicles and radiation-induced tissue injury, which will be beneficial to explore new treatment strategies for radiationinduced tissue injury. METHODS: Databases of PubMed and CNKI were retrieved with the keywords of “extracellular vesicles, radiation-induced tissue damage (bone, brain, intestine, etc.), WNT signal” in Chinese and “radiation-induced tissue injury, extracellular vesicles, tissue repair and regeneration, vascular endothelial cells, bystander effects” in English. The retrieval time was from 1989 to 2020. After initial screening of titles and abstracts, irrelevant articles were excluded, and 61 eligible articles were included for result analysis. RESULTS AND CONCLUSION: Extracellular vesicles are membrane-closed vesicles that are naturally released from cells under normal physiological or abnormal pathological conditions. On the one hand, under pathological conditions, radioactive tissue damage cannot be separated from the mediation of extracellular vesicles; on the other hand, extracellular vesicles carrying information molecules can promote the repair of radioactive tissue damage. Therefore, in the field of radioactive tissue damage repair and regeneration, extracellular vesicles have the potential to become a new cell-free therapy, but whether it can be applied to clinical use requires more in-depth research and exploration.

Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia / 北京大学学报(医学版)

OBJECTIVE@#To detect the ectodysplasin A (EDA) gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with EDA gene mutation.@*METHODS@#Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the EDA gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of EDA gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each EDA gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with EDA gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared.@*RESULTS@#Eight out of twelve HED families were identified to carry EDA gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs*73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226*) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with EDA gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (P>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence.@*CONCLUSION@#This study detected novel EDA gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of EDA gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.

Association between multivitamin supplementation and mortality among patients with Ebola virus disease: an international multisite cohort study

Introduction: Micronutrient supplementation is recommended in Ebola Virus Disease (EVD) care; however, there is limited data on its therapeutic effects. Methods: This retrospective cohort study included patients with EVD admitted to five Ebola Treatment Units (ETU) in Sierra Leone and Liberia during September 2014 to December 2015. A uniform protocol was used to guide ETU care, however, due to supply limitations, only a subset of patients received multivitamins. Data on demographics, clinical characteristics, and laboratory testing was collected. The outcome of interest was facility based mortality and the primary predictor was multivitamin supplementation initiated within 48 h of admission. The multivitamin formulations included: thiamine, riboflavin, niacin and vitamins A, C, and D3. Propensity score models (PSM) were used to match patients based on covariates associated with multivitamin administration and mortality. Mortality between cases treated and untreated within 48 h of admission were compared using generalized estimating equations to calculate relative risk with bootstrap methods employed to assess statistical significance. Results: There were 424 patients with EVD who had sufficient treatment data for analysis, of which 261 (61.6%) had daily multivitamins initiated within 48 h of admission. The mean age of the cohort was 30.5 years and 59.4% were female. In the propensity score matched analysis, mortality was 53.5% among patients receiving multivitamins and 66.2% among patients not receiving multivitamins, resulting in a relative risk for mortality of 0.81 (p=0.03) for patients receiving multivitamins. Conclusion: Early multivitamin supplementation was associated with lower overall mortality. Further research on the impact of micronutrient supplementation in EVD is warranted

Serum- and glucocorticoid-inducible kinase 3 is a potential oncogene in nasopharyngeal carcinoma / Quinase 3 sérica induzida por glicocorticoide é um potencial oncogene no 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.

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.

Neuroanatomical Circuitry between Kidney and Rostral Elements of Brain: a Virally Mediated Transsynaptic Tracing Study in Mice / 华中科技大学学报（医学）（英德文版）

The identity of higher-order neurons and circuits playing an associative role to control renal function is notwell understood.We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3~ days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice.PRV-614 infected neurons were detected in a number of mesencephalic (e.g.central amygdala nucleus),telencephalic regions and motor cortex.These divisions included the preoptic area (POA),dorsomedial hypothalamus (DMH),lateral hypothalamus,arcuate nucleus (Arc),suprachiasmatic nucleus (SCN),periventricular hypothalamus (PeH),and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN).PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH,Arc,SCN,PeH,PVN,the anterodorsal and medial POA.A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic.PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin.These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

The theory of homogeny of liver and kidney in the treatment of kidney and liver fibrosis / 中国结合医学杂志

Chronic kidney disease (CKD) and chronic liver disease are both very harmful to human health almost all over the world, which lead to the fibrosis of the two organs ultimately. Currently, there are few satisfactory therapeutic methods in treating the two diseases. Some research works from Chinese medicine and Western medicine were done in the area recently, the results showed that kidney and liver fibrosis shared similar biological signals and events such as epithelial-mesenchymal transition (EMT) and transforming growth factor β 1, the same herbal mesenchymal medicine exhibited significantly improving effects on both liver fibrosis and kidney fibrosis by involving similar mechanism. This coincides with the theory of homogeny of Liver (Gan) and Kidney (Shen) of Chinese medicine. It would provides new clues in exploring the treatment of liver fibrosis and kidney fibrosis.

Long-term Impact of Intrauterine MCMV Infection on Development of Offspring Nervous System / 华中科技大学学报（医学）（英德文版）

This study examined the impacts of intrauterine murine cytomegalovirus (MCMV) infection on the long-term learning and memory of offspring.Sexually matured male and female BALB/C mice without MCMV infection were identified by ELISA and then mated.Seventy pregnant mice were randomly divided into the virus group (n=40) and the control group (n=30),in which the pregnant mice were subjected to placenta inoculation of MCMV suspension (1 μL,1 × 106 PFU) or the same amount of cell culture medium,respectively,at gestational age of 12.5 days.Some pregnant mice [virus group (n=20),control group (n=l5)] were sacrificed by cervical dislocation at gestational age of 18.5 days,and the head circumference and brain weight of the mouse fetuses were measured,and the MCMV infection in their brain tissues was detected by PCR.The other pregnant mice [virus group (n=20),control group (n=15)] delivered naturally,and the learning and memory capability of the offspring at 70-day-old was analyzed by Morris water maze test.The results showed that 28.57％ mouse fetuses in the virus group developed viral infection in the brain.Their head circumference and brain weight were significantly reduced as compared with those in the control group (P＜0.01).The Morris water maze test revealed that the mouse offspring in the control group found the platform with straight-line trajectories after training.In contrast,the counterparts in the virus group intended to enter the central area,but looked for the platform with a circular trajectory.And the infected mice exhibited prolonged swimming distance and swimming latency (P＜0.01).It was concluded that:(1) placenta inoculation of MCMV can cause fetal brain infection and intrauterine development retardation; (2) the offspring of MCMV placenta inoculation mice showed a long-term decline in learning and memory capability.

Effect of Human Cytomegalovirus on Invasive Capability of Early Pregnant Extravillous Cytotrophoblasts / 华中科技大学学报（医学）（英德文版）

The effect of human cytomegalovirus (HCMV) on invasive capability of early pregnant extravillous cytotrophoblasts (EVTs) was investigated in vitro.Primary EVTs were obtained by complex phosphoesterasum digestion and gradient centrifugation from villous tissue aseptically taken from healthy pregnant women.Cytokeratin7 (CK7),vimentin (Vim) and c-erbB-2 were immunocytochemically detected to identify source of cells,and HCMVpp65 antigen was assayed to determine the infection state of primary EVTs by immunocytochemical staining.The EVTs were divided into two groups:control group and HCMV group,and the expression of c-erbB-2,matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins was detected in two groups by immunocytochemistry and Western blotting.Enzymic activity changes of MMP-2 and MMP-9 were tested by gelatin zymography in primary EVTs infected with HCMV.The invasion of primary EVTs was detected by cell invasion assay in vitro after they were infected by HCMV.The cell source identification showed that the cells obtained were highly-pure primary EVTs,and primary EVTs could be infected by HCMV.Primary EVTs could express c-erbB-2,MMP-2 and MMP-9 proteins,and as compared with control group,the protein expression was decreased significantly in HCMV groups (P＜0.05).Primary EVTs could secrete active MMP-2 and MMP-9 in vitro,and the activity of two MMPs was decreased significantly in HCMV groups (P＜0.05).The in vitro cell invasion assay showed that the number of primary EVTs permeating Matrigel in HCMV group was decreased (P＜0.05).We are led to conclude that HCMV can infect primary EVTs and inhibit their invasion capability,suggesting that the impaired EVT's invasion capability might be related to the abnormal expression of c-erbB-2,MMP-2and MMP-9 proteins.

Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway / 华中科技大学学报（医学）（英德文版）

This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α)expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells.PANC-1 cells were divided into three groups: Control group,insulin group and insulin+YC-1(a pharmacological inhibitor of HIF-1α)group in terms of different treatments.Cells in the insulin group or insulin+YC-1 group were treated with insulin(0.1,1,10 and 100 nmol/L)alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1,0.1,1,10 and 100μmol/L).HIF-1α mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively.Cell proliferation and invasion were measured by using growth curve and invasion assay,respectively.Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1α protein expression,and YC-1 could dose-dependently block this effect.However,neither insulin nor YC-1 altered HIF-1α mRNA levels in PANC-1 cells.Moreover,insulin could enhance the proliferation and invasion of PANC-1 cells,while YC-1 could weaken this effect.It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment.The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1αprotein.

In vitro Study on Human Trophoblast Cells Infected with HCMV / 华中科技大学学报（医学）（英德文版）

Human trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV.Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient.Cells and purity were identified by using immunocytochemistry assay with anti-CK7,Vim and β-hCG antibodies.HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection(p.i.).The results showed that highly purified trophoblast cells were obtained.Specific virus replication was increased dramatically at the 24th h p.i.,and then increased slowly during 48 h and 72 h.Apoptosis rate of trophoblast cells infected with HCMV was(34.68±3.14)% at 24th h p.i.,while that in control group was(15.32±2.34)%(P<0.05).It was suggested that highly purified trophoblast cells can be isolated by the simplified cell purification method.HCMV can infect human trophoblast cells,and be quickly replicated,resulting in the accelerated apoptosis of human trophoblast cells during early time.

Expression of NALP3 in the Spleen of Mice with Portal Hypertension / 华中科技大学学报（医学）（英德文版）

This study examined the mRNA expression of NALP3 in the spleen of the mice with hypersplenism due to portal hypertension(PH).The mouse hypersplenism models were established by oral administration of tetrachloromethane(2 mL/kg/week for 12 weeks by oral gavage).All the mice were randomly divided into a control group and an experimental group.The blood routine test was conducted,spleen index was calculated and spleen was histologically examined.Portal vein sera were taken for detection of the level of uric acid.The mRNA expressions of NALP3 and IL-1β in the spleen were detected by reverse transcriptase-polymerase chain reaction(RT-PCR).The results showed that the platelet count was significantly lower in the experimental group[(674±102)× 109/L]than in the control group[(1307± 181)× 109/L](P<0.05),while the spleen index was significantly higher[(9.83±1.36)μg/g]in the experimental group than in the control group[(4.11±0.47)μg/g](P<0.05).The histopathological changes of spleen followed the pattern of congestive splenomegaly.No significant difference was found in the uric acid level in the portal vein between the control group and the experiment group.The mRNA expressions of NALP3 and IL-1β were up-regulated significantly in the spleen in the experimental group as compared with those in the control group(P<0.05).It was concluded that NALP3 and IL-1β may play important roles in the pathogenesis of hypersplenism.