Characteristics of the means and methods used in soccer training / Características dos meios e métodos utilizados no treinamento de futebol / Características de los medios y métodos utilizados en el entrenamiento de fútbol

ABSTRACT Introduction The correct understanding and implementation of the tasks set by the coach for the player are achieved through a wide variety of training sessions. To date, the question of training effectiveness and the preparation of professional soccer players for matches has not been sufficiently studied. Objective Study the means and methods used in soccer training. By comparison, find out which method is most effective in achieving a positive result during the game and maintaining the players' health. Methods The study used mathematical and physical methods and comparative analysis. In the study, the main training methods in a team were considered. A comparative analysis was made between two types of individual soccer players' training to improve physical and technical parameters. Result We established which parameters influence the choice of the training scheme. The effectiveness of both training systems is proven by the statistical indicators of soccer players who train according to these methods. Conclusion The effectiveness of the training methodology chosen by a soccer player depends on his initial physical abilities and professional skills. The study's practical significance is determined by the fact that the proposed methods can be used in training professional athletes. Evidence level II; Therapeutic studies - outcomes research.

RESUMO Introdução A correta compreensão e implementação das tarefas definidas pelo treinador para o jogador é alcançada através de uma ampla variedade de sessões de treinamento. Até hoje, a questão da eficácia do treinamento e a preparação dos jogadores profissionais de futebol para os jogos não foi suficientemente estudada. Objetivo Estudar os meios e métodos utilizados no treinamento de futebol e, por comparação, descobrir qual dos métodos é mais eficaz para obter um resultado positivo durante o jogo e manter a saúde dos jogadores. Métodos O estudo utilizou métodos matemáticos e físicos, assim como análise comparativa. No decorrer do estudo, foram considerados os principais métodos de treinamento em uma equipe. Foi realizada uma análise comparativa entre dois tipos de treinamento individual de jogadores de futebol, objetivando melhorar parâmetros físicos e técnicos. Resultado Foram estabelecidos quais parâmetros influenciam a escolha do esquema de treinamento. A eficácia de ambos os sistemas de treinamento é comprovada pelos indicadores estatísticos dos jogadores de futebol que treinam de acordo com estes métodos. Conclusão A eficácia da metodologia de treinamento escolhida por um jogador de futebol depende de suas habilidades físicas iniciais e habilidades profissionais. O significado prático do estudo é determinado pelo fato de que os métodos propostos podem ser utilizados no treinamento de atletas profissionais. Evidência nível II; Estudos terapêuticos - pesquisa de resultados.

RESUMEN Introducción La correcta comprensión y ejecución de las tareas establecidas por el entrenador para el jugador se consigue a través de una amplia variedad de sesiones de entrenamiento. Hasta hoy, la cuestión de la eficacia del entrenamiento y la preparación de los futbolistas profesionales para los partidos no se ha estudiado suficientemente. Objetivo Estudiar los medios y métodos utilizados en el entrenamiento de fútbol y, por comparación, averiguar qué método es más eficaz para conseguir un resultado positivo durante el juego y mantener la salud de los jugadores. Métodos El estudio utilizó métodos matemáticos y físicos, así como análisis comparativos. En el transcurso del estudio, se consideraron los principales métodos de formación en un equipo. Se realizó un análisis comparativo entre dos tipos de entrenamiento individual de jugadores de fútbol, con el objetivo de mejorar los parámetros físicos y técnicos. Resultado Se estableció qué parámetros influyen en la elección del esquema de entrenamiento. La eficacia de ambos sistemas de entrenamiento queda demostrada por los indicadores estadísticos de los futbolistas que entrenan según estos métodos. Conclusión La eficacia de la metodología de entrenamiento elegida por un futbolista depende de sus capacidades físicas iniciales y de sus habilidades profesionales. La importancia práctica del estudio viene determinada por el hecho de que los métodos propuestos pueden utilizarse en el entrenamiento de atletas profesionales. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Influence of family support on the physical activities and motor skills of children and adolescents / 中国学校卫生

Objective@#To explore the relationship between family background and parental support and adolescents physical activity and motor skills, and to provide a corresponding theoretical basis for the health promotion of children and adolescents in China.@*Methods@#From November to December 2019, 140 junior high school students aged 12-14 years in a junior high school in Shanxi Province were selected, and physical activity was recorded for 7 days using an ActiGraph GT3X+ accelerometer. The Activity Support Scale for Children (ACTS CN) was used to evaluate parents support and attitude towards children s activities and behaviors. The Canadian Agility and Movement Skill Assessment (CAMSA) was used to evaluate the motor ability development of adolescents.@*Results@#The daily participation time in moderate to vigorous physical activity (MVPA) was (40.57±13.54) and (31.65± 9.98 ) min for males and females, respectively, with a statistically significant difference ( t =4.44, P <0.05); The average motor skill scores were (10.8±1.9) and (10.1±1.9), and completion times were (17.7±2.8) and (19.1±2.5)s, respectively; regression analyses showed that mothers education, monthly household income, mothers attention to children s exercise and fathers support for club participation were all significantly associated with adolescents MVPA ( B =-0.28,-0.16,-0.16, 0.18, P <0.05). Parental provision of exercise space was significantly associated with motor ability ( r =0.17, 0.17, P <0.05).@*Conclusion@#Parents with higher levels of education have a more positive influence on their children s physical activity participation. Parental presence can contribute to a certain extent to the level of physical activity of adolescents, and a supportive environment provided from parents can positively influence the level of motor skills of adolescents.

Bone marrow mesenchymal stem cell derived exosomes miR-21-5p promotes proliferation, migration and invasion of prostate cancer PC-3 cell by downregulating PHLPP2 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of exosome originated from bone marrow mesenchymal stem cell (BMSCs) on proliferation, migration and invasion of prostate cancer PC-3 cell and its mechanism. Methods: qPCR was used to detect the expression level of miR-21-5p in prostate cancer cell lines. The morphology of exosomes isolated from BMSCs was observed with an electron microscope. Western blotting was used to detect the expressions of exosome surface markers and the epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin). Dual luciferase reporter gene experiment was used to detect the targeted regulation relationship between miR-21-5p and PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2). PC-3 cells were co-cultured with 10 μl BMSCs exosomes suspension (Exo group), transfected with sh-PHLPP2 or antagomiR, then CCK-8 and Transwell experiments were used to detect changesinproliferation,migrationandinvasionofPC-3cell.Results: miR-21-5p was highly expressed in prostate cancer PC-3 cell line. The exosomes in the supernatant of BMSCs culture fluid were successfully isolated, and the typical vesicle-like structures of exosomes were observed under transmission electron microscope. Exosomes expressed specific proteins such as CD9, CD63 and CD81. In the Exo group, the proliferation, invasion, migration, as well as the expressions of N-cadherin, Vimentin and miR-21-5p in PC-3 cells were significantly higher than those in the control group (all P<0.05). PHLPP2 is a target gene of miR-21-5p. Compared with the control group, the expression of PHLPP2 in PC-3 cells of Exo group and sh-PHLPP2 group was significantly reduced (0.66±0.09, 0.42±0.05 vs 1.09±0.08, all P<0.01); cell viability, invasion and migration were significantly improved (all P<0.01); and E-cadherin expression level was significantly reduced while N-cadherin and Vimentin expressions were significantly increased (both P<0.05). Conclusion: miR-21-5p is highly expressed in prostate cancer PC-3 cell line. BMSC exosome miR-21-5p can increase the proliferation, migration and invasion ability of PC-3 cells through targeted down-regulation of PHLPP2.

131 I therapy without antithyroid drug pretreatment for patients with severe hyperthyroidism: Analysis of 637 cases / 解放军医学杂志

[Abstract] Objective To evaluate the safety and long-term results of131I therapy without antithyroid drug (ATD) pretreatment for patients with severe hyperthyroidism (SH). Methods Clinical data of 637 patients with SH, admitted in the Department of Nuclear Medicine, the former 307th Hospital of Chinese PLA from Jan. 1975 to Dec. 2014, treated with131I without ATD pretreatment and followed up for more than one year, were recruited in present study. SPSS 20.0 software was used to analyze the therapeutic efficacy, serum levels of thyroid hormone (TH) and thyroid therapeutic activity, etc. Results Based on the clinical characteristics, the 637 patients were divided into seven groups: severe thyroid dysfunction, thyrotoxic heart disease, complicated with severe liver dysfunction, complicated with large goiter, complicated with huge goiter, complicated with severe cytopenia, and complicated with thyrotoxic periodic paralysis, etc. Five hundred and Forty cases (84.8%) were cured, 53 cases (8.3%) with complete remission, and 44 cases (6.9%) with incomplete remission. Hypothyroidism was noted in 363 cases (57.0%). No significant clinical worsening was found in 637 patients after131I therapy. The thyroid hormones (TH) level returned to normal within 12 months after131 I therapy in 510 patients (80.1%). The efficacy of131I therapy was closely correlated to the administered activity of131I. The dose of131 I therapy was 2.59 to 11.11MBq per gram of thyroid with an average of (3.82±0.80)MBq, and the total131I activity administrated for the individuals was 85.1-3496.5MBq with an average of (447.7±407.0)MBq. The cure rate after one dose of131I therapy was 81.8%. The serum TH level was decreased significantly in patients with severe jaundice by lithium carbonate prescribed shortly before and after131I therapy. The131I therapy instead of surgical treatment is safe and effective for those patients complicated with huge goiter and heart disease and unsuitable for surgery.131I therapy does not affect fertility, and there have been 57 patients who have given birth of 59 healthy babies. Conclusion131I therapy without ATD pretreatment is safe and effective for patients with SH. Based on comprehensive treatment, the individualized131I therapy for such patients should be considered as early as possible.

Di (2-ethylhexyl) phthalate-induced hypospadias in SD rats is related with Mafb expression: a transcriptome profiling-based study / 南方医科大学学报

OBJECTIVE@#To investigate the transcriptome profile of genital tubercles (GTs) in male SD rats and explore the mechanism of hypospadias induced by Di (2-ethylhexyl) phthalate (DEHP).@*METHODS@#Forty time-pregnant SD rats were randomly divided into 4 equal groups, namely GD16 group and GD19 group (in which the male GTs were collected on gestation day[GD]16 and GD19 for RNA-seq, respectively), control group and DEHP exposure group (with administration of oil and 750 mg/kg DEHP by gavage from GD12 to GD19, respectively).In the control and DEHP exposure groups, the GTs were collected from the male fetuses on GD19.5, and scanning electron microscopy and HE staining were used to observe the morphological changes.The differentially expressed genes (DEGs) in the GTs were screened using lllumina HiSeq 2000 followed by GO and KEGG enrichment analyses to characterize the transcriptome profile.Immunofluorescence assay was performed to verify the DEGs (Mafb) identified by RNA-seq results.Immunofluorescence assay and Western blotting were used to examine the expression levels of Mafb in the penile tissue.@*RESULTS@#A total of 1360 DEGs were detected in the GTs between GD16 group and GD19 group by RNA-seq.Among these genes, 797 were up-regulated and 563 were down-regulated.These DEGs were mainly enriched in the cell adhesion plaque signaling pathway, axon guidance signaling pathway, and extracellular matrix receptor signaling pathway.Compared with that in GD16 group, Mafb was significantly up-regulated in GD19 group, which was consistent with the sequencing results.Mafb and β-catenin were significantly down-regulated in DEHP-exposed group compared with the control group ( < 0.01).@*CONCLUSIONS@#Mafb expression increases progressively with the development of GTs in male SD rats.DEHP exposure causes significant down-regulation of Mafb and β-catenin, suggesting that β-catenin signaling pathway that affects Mafb is related to DEHP-induced hypospadias in SD rats.

Comparative study on the inhibitory effect of dual specific oncolytic adenovirus and doxorubicin on breast cancer cells / 中国肿瘤生物治疗杂志

@#Objective: To explore the difference in the proliferation inhibition of doxorubicin and dual specific oncolytic adenoviruses (Ad-VT, Ad-T, Ad-VP3 and d-Mock) on breast cancer cells and normal mammary cells. Methods: The proliferation inhibition rates of doxorubicin and recombinant adenovirus(Ad-VT, Ad-T, Ad-VP3and Mock) on breast cancer cells were detected through WST-1 experiment, and the effects of two drugs on the inhibitory rates of normal mammary epithelial cells were also detected. Moreover, the apoptosis rates of doxorubicin and oncolytic adenoviruses on breast cancer cells and normal mammary epithelial cells were evaluated by Annexin V flow cytometry, Hoechst and JC-1 staining, and the difference in the apoptosis rates were also compared. Results: All the recombinant adenovirus could effectively suppress the proliferation of breast cancer cells (P<0.05 or P<0.01), the inhibition effects followed the order ofAd-VT>Ad-T>Ad-VP3>Ad-MOCK, and the inhibition effect was positively correlated with time. Doxorubicin could also effectively suppress the proliferation of breast cancer cells (P<0.05 or P<0.01), and the inhibition effect was markedly enhanced with the increases in does and time. However, doxorubicin also showed strong inhibition effect on the normal mammary epithelial cells, and the inhibition rate achieved 80% under 72 h and 5 ug/ml doxorubicin, while that of oncolytic adenovirus Ad-VT on MCF-10A was 20% at 72 h. The apoptosis effects of oncolytic adenoviruses-induced breast cancer cellwere increased with time, and the apoptosis rate efficiency followed the order of Ad-VT>Ad-T>Ad-VP3>Ad-MOCK, but they displayed low ability to induce normal mammary cell apoptosis. The apoptosis effects of doxorubicin-induced breast cancer cell were similar to that of the normal mammary epithelial cell (P <0.05 or P<0.01), which followed the dose of 0.05<0.5<5 μg/ml. Conclusion: Dual specific oncolytic adenoviruses can effectively suppress the proliferation of breast cancer cells, but they have low inhibition on normal mammary cells, which have displayed superior safety and provide a new method for the biotherapy of tumor.

Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review

A comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81) and externally (0.49-0.87). Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.

Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Adult Patients with Diabetes: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus (DM) patients with episodes of recurrent severe hypoglycemia,by using meta-analysis to synthesize data across studies.PubMed,EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia.Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method.Effect sizes,which are the standardized differences between the experimental group and the control group,were calculated.Of the 853 studies,7 studies met the inclusion criteria.Compared with control subjects,the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients,and poor performance of processing speed in type 2 DM patients.There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence,executive function,processing speed and psychomotor efficiency.Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia,whereas general intelligence,executive function,and psychomotor efficiency are spared.

Current situation and prospect of fertility preservation in male cancer patients / 中国医师杂志

With the rapid development of tumor subjects and the advance of medical technology,tumor mortality is declining in spite of the increase in tumor incidence.The male survivors pay more and more attention to their prognosis to improve the quality of their life.In the meantime,whether they could produce their own offspring become the main concern of tumor patients with good prognosis.However,until now,male tumor patients,their relatives,different social sectors and even some of our health workers,havent noticed the importance of fertility preservation and long-term fertility desires of male patients with tumor which will lead to declined or even irreversible sterility induced by the lack of fertility preservation before anti-tumor therapy.It's an important way to do fertility counseling,learn the risk of their treatment plans and choose the appropriate technique of fertility preservation which will improve prognosis quality of life of male tumor patients.This article will review the effects of tumor and the treatment on male fertility,their subjective needs and concerns,main methods for fertility preservation and the domestic and foreign research present situation.

Research progress of the IDO in reproductive immunology / 中国医师杂志

Indoleamine 2,3-dioxygenase (IDO) is a kind of immune regulation enzyme.IDO is the only rate-limiting enzyme that can catalyze the oxidative clearage of indole ring in tryptophan and its catabolism along the kynurenine pathway.IDO1 is one of the important mechanisms in maternal immune tolerance,which participates in the regulation of maternal-fetal immune relationship.The newly discovered IDO2 also plays an important role in this relationship.The abnormal expression of IDO2 is associated with the male infertility.

Metabolic analysis of the effect of rheum on a taurocholate-induced acute pancreatitis rat model

ABSTRACT The effects of rheum on serum parameters in a taurocholate-induced acute pancreatitis (AP) rat model were investigated using pathological and biochemical tests, and a proton nuclear magnetic resonance (1H NMR)-based metabonomic strategy. Healthy rats and rats with AP were either treated with rheum (7.5% at a dose of 1.5 g/kg) or left untreated. Serum samples were collected from the AP and rheum-treated groups at 6, 12, and 24 h after treatment. The effect of rheum on pathological changes in the pancreatic was investigated to validate the AP model. We obtained 1H NMR spectra and analyzed the results using the partial least squares discriminant method. The results of the pathological and metabolic analyses revealed an amelioration of multiple metabolic abnormalities and an increase in the aerobic respiration ratio after treatment, compared with the AP groups. These results were attributed to improvements in energy supply and the elimination of metabolic products. The study also promoted NMR-based metabonomic analysis as a feasible method of assessing traditional Chinese drugs.

Safety of the offspring conceived by assisted reproductive technology with cryopreserved donor sperm / 中华男科学杂志

<p><b>Objective</b>To investigate the pregnancy outcomes of assisted reproductive technology (ART) with cryopreserved donor sperm and the safety of the offspring thus conceived.</p><p><b>METHODS</b>The Human Sperm Bank of CITIC Xiangya Hospital provided cryopreserved donor semen to 31 reproductive centers in China between January 2006 and December 2012, with which 50247 ART cycles were accomplished. We compared the rates of birth defects and spontaneous abortion of intracervical insemination (ICI), intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI).</p><p><b>RESULTS</b>A total of 39 047 ART cycles were performed by artificial insemination with cryopreserved donor sperm, including 36 674 cycles of ICI and 2 372 cycles of IUI. Among the 8 612 clinical pregnancies achieved by ICI, there were 917 cases of spontaneous abortion (at <28 gestational wk) (10.6%) and 6133 live births, with 43 cases of birth defect (0.70%). Of the 547 clinical pregnancies achieved by IUI, there were 41 cases of spontaneous abortion (7.5%) and 426 live births, with 2 cases of birth defect (0.47%). Totally, 11 200 cycles of IVF and ICSI were accomplished with cryopreserved donor sperm. Of the 5 860 clinical pregnancies achieved by IVF, there were 456 cases of spontaneous abortion (7.8%) and 5089 live births, with 55 cases of birth defect (1.08%). Among the 350 clinical pregnancies achieved by ICSI, there were 30 cases of spontaneous abortion (8.6%) and 229 live births, with 3 cases of birth defect (1.31%). The birth defect rate of ART with cryopreserved donor sperm was significantly lower than that published by the Chinese Ministry of Health (0.86% vs 1.53%,P<0.01).</p><p><b>CONCLUSIONS</b>The safety of the offspring conceived by ART with cryopreserved donor sperm is controllable.</p>

HIV related risky behavioral network and molecular epidemiology of HIV seroconcordant couples in Taizhou municipality of Zhejiang Province / 浙江大学学报·医学版

<p><b>UNLABELLED</b>Obstract: To characterize and analyze risky sexual networks and genetic scales to potential HIV transmission for HIV seroconcordant couples in Taizhou municipality of Zhejiang Province.</p><p><b>METHODS</b>HIV seroconcordant positive couples were invited as index cases to participate in an egocentric survey on HIV related risky behavior and behavioral network prior to HIV diagnosis during 2008-2011. Within-couple HIV transmission pairs were determined by the combination of both behavioral and phylogenetic analysis.</p><p><b>RESULTS</b>Totally 27 HIV seroconcordant couples were enrolled in this study. Male spouses were more likely to report having two or more sexual partners in the past years prior to HIV diagnosis than female spouses (88.9% vs. 37.0%). Among 27 couples, 20 couples including 17 couples by male but not female spouses, 3 couples by female but not male spouses reported having two or more sexual partners (i.e., multiple sexual partners) prior to HIV diagnosis; and 7 couples by both spouses reported having multiple sexual partners. Twenty four of 27 sexual networks were determined to be HIV transmission pairs (20) or potential transmission pairs (4), 3 couples were subtyped with discordant HIV subtypes or large genetic distance and thus had different sources of HIV transmissions. In addition, among 27 concordant couples, HIV drug resistance (HIVDR) or primary HIVDR existed in 6 ART-naïve participants in 4 networks; among them, 2 networks were determined to be potential HIVDR transmission couple pairs.</p><p><b>CONCLUSIONS</b>The HIV strains isolated in HIV infected spouses characterized with diversity and CRF01_AE was the main strain subtype. One of the spouses with risky behavior infected HIV was the main route of transmission to other spouses through unprotected sexual contacts. HIVDR was isolated from some HIV infected individuals, suggesting the risk for HIVDR transmission in married couples. The results provide enhanced evidence for urgent development of tailored prevention strategies, such as couple-based HIV counseling and testing services to reduce HIV secondary transmission.</p>

Effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration of laryngeal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of histone deacetylase 6 (HDAC6) in laryngeal squamous cell carcinoma, and to analyze the effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration of laryngeal squamous cell carcinoma cell line Hep-2 cells, and to explore their possible molecular mechanisms.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expression of HDAC6 protein in 55 cases of laryngeal squamous cell carcinoma and 20 cases of normal laryngeal mucosa. HDAC6 siRNA and control siRNA were transfected into Hep-2 cells via lipofectamine 2000, and the interfering effect was analyzed using Western blotting. The effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration were determined by cell counting kit-8 (CCK-8), flow cytometry and Boyden chamber, respectively. Finally, Western blotting was used to detect the expressions of cell cycle, proliferation and migration related proteins.</p><p><b>RESULTS</b>There was a high level expression of HDAC6 protein in laryngeal squamous cell carcinoma, and its expression was not related to age and sex of the patients (P > 0.05), but closely associated with the degree of histological differentiation, TNM staging and lymph node metastasis (P < 0.05). HDAC6 siRNA effectively down-regulated the expression of HDAC6 protein in laryngeal squamous cell carcinoma cell line Hep-2 cells, and downregulation of its expression obviously inhibited cell proliferation, arrested cell cycle at G(0)/G(1) phase and decreased cell migration ability in Hep-2 cells. Additionally, the downregulation of HDAC6 protein expression markedly decreased the expressions of cyclin D1, cyclin E, cdk2 and MMP-9 proteins, but increased the expressions of p21 and E-cadherin proteins.</p><p><b>CONCLUSIONS</b>HDAC6 may play a pivotal role in the carcinogenesis and development of laryngeal squamous cell carcinoma. The downregulation of HDAC6 expression-mediated cell proliferation inhibition, cell cycle arrest and decreased cell migration ability may be closely associated with the decrease of cyclin D1, cyclin E, cdk2 and MMP-9 proteins and increase of p21 and E-cadherin proteins.</p>

Arsenic trioxide restores ERα expression in ERα-negative human breast cancer cells and its treatment efficacy in combination with tamoxifen in xenografts in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the demethylation effect of arsenic trioxide (As2O3) on ERα-negative human breast cancer MDA-MB-435s cells and its possible mechanisms, and to observe its treatment efficacy in combination with tamoxifen (TAM) after ERα re-expression.</p><p><b>METHODS</b>MTT assay was used to examine the inhibitory effect of As2O3 treatment alone or in combination with TAM on cell proliferation. A nude mouse xenograft model was used to further examine the treatment efficacy in vivo. MSP was used to detect the methylation status of ERα gene after treated with As2O3 in MDA-MB-435s cells and the transplanted tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and Erα. Western bolt was used to detect the DNMT1 and ERα protein expression. The diameter of xenograft tumors was measured weekly, and the tumor growth curve was drawn.</p><p><b>RESULTS</b>The level of proliferation of the MDA-MB-435s cells was significantly suppressed after treatment with different concentration of As2O3 alone or As2O3 combined with TAM, and the 4 µmol/L As2O3 + TAM treatment for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 µmol/L As2O3 had demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein expression was inhibited and accompanied by ERα mRNA and protein re-expression. The unmethylation specific bands of ERα gene were enhanced after treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERα mRNA and protein re-expression. An significant decrease of volume and weight of the xenograft tumors in the As2O3 treated alone or combined with TAM groups was observed compared with those of the normal saline group or TAM alone group (P < 0.05), and the 4 mg/kg As2O3 + TAM group had the highest inhibition rate of tumor weight (79.5%) and volume (76.4%).</p><p><b>CONCLUSIONS</b>ERα can be re-expressed in ERα-negative breast cancer MDA-MB-435s cells after treated with As2O3 by inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine therapy after ERα re-expression. As2O3 combined with TAM may provide a new therapeutic approach for patients with ERα-negative breast cancer in the clinic.</p>

Expression and significance of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase in non-melanoma skin cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression and significance of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-2, TIMP-1) in non-melanoma skin cancer (NMSC).</p><p><b>METHODS</b>Thirty six patients with squamous cell carcinoma (SCC) and 32 patients with basal cell carcinoma (BCC), confirmed by pathology, were selected, and 30 cases of normal skin were selected as control. The expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in all samples were examined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The expression rate, expression intensity and expression level of each factor were recorded. The results were compared between the groups.</p><p><b>RESULTS</b>The expression rates of MMP-2 and MMP-9 in the control group were 30.0% and 36.7%, the expression levels of MMP-2 and MMP-9 in the control group were 57.216 ± 12.785 and 59.318 ± 13.262, all significantly lower than those in the tumor edge and center of the SCC and BCC groups (P < 0.01). The expression rates of TIMP-1 and TIMP-2 in the control group were 96.7% and 100%, their expression levels were 121.738 ± 25.516 and 122.612 ± 25.964, all significantly higher than those in the SCC and BCC groups (P < 0.01). The expression levels of MMP-2 and MMP-9 in the tumor center and edge of SCC group were significantly higher than those in the corresponding parts of the BCC group, while the expression levels of TIMP-1 and TIMP-2 were significantly lower than those in the BCC group (P < 0.01). The expression levels of MMP-2 and MMP-9 in the tumor edge of the SCC and BCC groups were significantly higher than those in the tumor centers (P < 0.01), while the expression levels of TIMP-1and TIMP-2 were significantly lower than those in the tumor centers (P < 0.01).</p><p><b>CONCLUSION</b>MMP-2, MMP-9 and TIMP-2, TIMP-1 may play an important role in the development, progression, invasion and metastasis of non-melanoma skin cancer.</p>

Silencing of Bmi-1 gene by RNA interference enhances sensitivity to doxorubicin in breast cancer cells.

The oncogene Bmi-1 is highly up-regulated in breast carcinoma and is found to be efficient in preventing apoptosis of the cancer cells. Doxorubicin is an important chemotherapeutic agent against breast carcinoma. However, the effective therapeutic response to doxorubicin is often associated with severe toxicity. The present study is targetted at developing a strategy to increase doxorubicin sensitivity to lower doses without compromising its efficacy. A stable cell line with a persistent silencing of Bmi-1 was established. MTT assay was performed to evaluate 50% inhibitory concentration (IC50) values of doxorubicin. Apoptosis was detected by FCM and the expression of related genes [phosphor-Akt (pAkt), totle-Akt (tAkt), Bcl-2 and Bax] was studied by Western blot. In vivo, the sensitivity of the tumor tissues against doxorubicin was evaluated by transplanted MCF-7 nude mice model and the apoptosis of tissue cells was detected by TUNEL assay. The expression of pAkt and Bcl-2 was down-regulated, whereas Bax was up-regulated in Bmi-1 silencing cells. The results obtained indicated that silencing of Bmi-1 can render MCF-7 cells more sensitive to doxorubicin which induced a significantly higher percentage of apoptosis cells in vitro and in vivo. All together these results clearly demonstrate that Bmi-1 siliencing combined treatment of doxorubicin might be a new strategy for biological treatment on breast cancer.

Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice.</p><p><b>METHODS</b>The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.</p><p><b>RESULTS</b>Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.</p>

Correlation of TOP2A gene expression and survival of breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the TOP2A RNA expression and the relationship of TOP2A protein expression with metastasis-free interval in breast cancer patients.</p><p><b>METHODS</b>TOP2A expression was analyzed prior to surgery in 86 patients. The level of TOP2A gene amplification was analyzed by fluorescence in situ hybridization (FISH), its RNA expression level with RT-PCR, and their correlation with TOP2A protein expression was assessed by immunohistochemistry (IHC). The correlation between RNA expression level and metastasis-free interval in breast cancer patients was also analyzed.</p><p><b>RESULTS</b>Aberrations (amplification or deletion) of TOP2A copy number was observed in 25.6% (22/86) of the cases. TOP2A protein expression was detected in 66.3% (57/86) of the samples. There was a significant correlation between the TOP2A RNA expression and protein expression (P < 0.001). TOP2A gene expression was significantly associated with the metastasis-free interval in the breast cancer patients (P = 0.001). There was no significant correlation between TOP2A gene amplification and TOP2A protein expression (P = 0.211).</p><p><b>CONCLUSIONS</b>TOP2A RNA level is an objective and reliable prognostic indicator in breast cancer.</p>