Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma / 中国医学科学院学报

Objective To investigate the role of ATP citrate lyase(ACLY)in the development of hepatocellular carcinoma(HCC)and the impact of this enzyme on the immune microenvironment of HCC.Methods We utilized the University of Alabama at Birmingham Cancer Data Analysis Portal and the Gene Expression Profiling Interactive Analysis to identify the changes in ACLY expression and prognosis across different tumor types from The Cancer Genome Atlas.With HCC as the disease model,we analyzed the ACLY expression in HCC samples from the gene expression database.Furthermore,we collected the clinical specimens from HCC patients to verify the mRNA and protein levels of ACLY.In addition,we conducted transcriptome sequencing after knocking down the expression of ACLY to analyze the differentially expressed genes and investigated the impact of ACLY expression interference on cell proliferation and other functions.Finally,we explored the correlations of ACLY with immune cells and immune infiltration in the tumor microenvironment,new antigens,and immune checkpoint genes.Results ACLY expression was significantly up-regulated in solid tumors including HCC(all P<0.05),and high ACLY expression was associated with overall survival rate in HCC(P=0.005).Furthermore,high ACLY expression affected the presence of immune cells(e.g.,tumor-associated fibroblasts)and the expression of genes involved in lipid metabolism(all P<0.05).Conclusions ACLY is closely related to the occurrence and development of HCC and lipid metabolism abnormalities.Moreover,it has a specific impact on the immune microenvironment of HCC.

Role and clinical significance of MLLT1 super elongation complex subunit in the occurrence and development of hepatocellular carcinoma / 解剖学报

Objective To investigate the role of MLLT1 in hepatocellular carcinoma (HCC)and its impact on the tumor immune microenvironment. Methods Multivariate Cox regression analysis and tumor gene analysis tools such as GEPIA and UALCAN were used to explore the expression of the MLLT1 gene and its prognostic significance in different tumors. Real-time PCR, Western blotting, and immunohistochemistry were used to investigate the differential expression of MLLT1 between HCC tumor tissue and normal tissue. MTT assay and cell cycle analysis were performed to assess the effect of MLLT1 knockdown on cell proliferation and cell cycle. The correlation between MLLT1 and immune cells, as well as immune infiltrates in the tumor microenvironment, and their correlation with immune neoantigens, immune checkpoints, tumor mutation burden, and microsatellite instability were also explored. Results The MLLT1 gene was found to be aberrantly expressed in various solid tumors including HCC, and its high expression was associated with poor prognosis in HCC. Knockdown of MLLT1 inhibited HCC cell proliferation and blocked the cell cycle. High expression of MLLT1 was found to affect the content of multiple immune cells, including CD4

Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice / 解剖学报

Objective To explore the effect of melatonin ( MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases ( PI3K)/protein kinase B ( Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the frypothalamus. Methods Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1 mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone (LH)were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in frypothalamus were detected by Real-time PCR and Western blotting. Results Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time ( P < 0. 05 ) , decreased significantly ovarian and uterine volume and index (P<0. 05) , decreased significantly serum LH levels (P<0. 05) , and decreased significantly mRNA and protein expression levels of the frypothalamic PI3K/Akt/mTOR pathway (P<0. 05). Conclusion Melatonin delays puberty initiation in mice by a mechanism that ma)' be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway.

Correlation between tumor necrosis factor-α and interleukin-1β in exhaled breath condensate and pulmonary function in chronic obstructive pulmonary disease / 中国热带医学

@#Abstract: Objective To explore the correlation between lung function in patients with chronic obstructive pulmonary disease (COPD) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels in exhaled breath condensate (EBC), and to provide a convenient methodological basis for the diagnosis and treatment of COPD and the determination of its efficacy. Methods A total of 81 COPD patients and 40 healthy controls were selected from the respiratory department of the Fourth Affiliated Hospital of Guangzhou Medical University from August 2020 to February 2022 as the research subjects. The COPD patients were divided into 41 cases in the acute exacerbation group and 40 cases in the remission group according to their status. All participants underwent lung function detection, venous blood and EBC collection, and the levels of TNF-α and IL-1β in EBC and venous blood were analyzed by enzyme-linked immunosorbent assay (ELISA), and correlation analysis was performed by Pearson correlation analysis method. Results The levels of TNF-α and IL-1β in EBC of in the acute exacerbation group, the healthy control group, the remission group were (5.16±0.18) pg/μL and (7.75±0.27) pg/μL, (2.66±0.31) pg/μL and (2.41±0.24） pg/μL, (3.61±0.29) pg/μL and (3.17±0.38) pg/μL, respectively. Compared with the healthy control group, the levels of TNF-α and IL-1β in EBC in the COPD acute exacerbation group were significantly higher than those in the healthy control group and the COPD remission group (F=9.451, 8.217, P<0.001). Serum tests were consistent with this result. Correlation analysis showed that the levels of TNF-α and IL-1β in EBC were significantly positively correlated with the level of serum inflammation levels (P<0.001), while significantly negatively correlated with lung function (P<0.001).  Conclusions TNF-α and IL-1β in EBC are potential biomarkers of inflammation in patients with COPD, and their detection can be used to effectively assess lung function in patients with COPD. 

Influence of gymnastic games on standing long jump / Influência dos jogos de ginástica em saltos em distância horizontal / Influencia de los juegos gimnásticos en el salto de longitud horizontal

ABSTRACT Introduction The standing long jump consists of four parts: pre-swing, take-off, flying, and landing. Objective Analyze the influence of gymnastics game fitness on standing long jump. Methods Eight kindergartens in a city were selected and divided into experimental and control groups. The children in the experimental group were intervened in gymnastics and game fitness modules. Each module was intervened in a rolling cycle in the morning and afternoon outdoor activities of children from June 1, 2021, to March 31, 2010, for nine months. Results During the intervention period, there was no significant difference between the experimental group and the control group (P > 0.05), but there was a significant difference between the experimental group and the girls before and after the experimental intervention (P < 0.05), while the difference between boys was not statistically significant, indicating that the range of ankle movement of girls was slightly more affected than boys during the fitness intervention. Conclusion With the increase in age and training time, the change range of joint angles of older children in the experimental group is significantly higher than that in the control group. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução O salto em distância horizontal consiste em quatro partes: corrida de aproximação, impulsão, voo e queda. Objetivo Estudar a influência da ginástica no salto em distância horizontal. Métodos Oito jardins de infância em uma cidade foram selecionados e divididos em um grupo experimental e um grupo de controle. As crianças do grupo experimental atuaram nos módulos de ginástica e de condicionamento físico. Cada módulo foi submetido a um ciclo contínuo de atividades ao ar livre de manhã e à tarde de atividades infantis, de 1º de junho de 2021 a 31 de março de 2010, por um total de 9 meses. Resultados Durante o período de intervenção, não houve diferença significativa entre o grupo experimental e o grupo controle (P > 0,05), mas houve diferença significativa entre o grupo experimental e as meninas antes e depois da intervenção experimental (P < 0,05), enquanto a diferença entre os meninos não foi estatisticamente significativa, indicando que a amplitude do movimento do tornozelo das meninas foi ligeiramente mais afetada do que a dos meninos durante a intervenção de condicionamento físico. Conclusão Com o aumento da idade e do tempo de treinamento, a faixa de variação do ângulo de articulação das crianças mais velhas no grupo experimental foi significativamente maior do que a do grupo de controle. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El salto de longitud horizontal consta de cuatro partes: carrera de aproximación, impulsión, vuelo y caída. Objetivo Analizar la influencia de la gimnasia en el salto de longitud de pie. Métodos Se seleccionaron ocho guarderías de una ciudad y se dividieron en un grupo experimental y otro de control. Los niños del grupo experimental realizaron módulos de gimnasia y fitness. Cada módulo intervino en un ciclo continuo de actividades al aire libre por la mañana y por la tarde desde el 1 de junio de 2021 hasta el 31 de marzo de 2010, durante nueve meses. Resultados Durante el período de intervención, no hubo diferencias significativas entre el grupo experimental y el grupo de control (P > 0,05), pero sí entre el grupo experimental y las chicas antes y después de la intervención experimental (P < 0,05), mientras que la diferencia entre los chicos no fue estadísticamente significativa, lo que indica que la amplitud de movimiento del tobillo de las chicas se vio ligeramente más afectada que la de los chicos durante la intervención de acondicionamiento físico. Conclusión Al aumentar la edad y el tiempo de entrenamiento, el rango de variación de los ángulos articulares de los niños mayores del grupo experimental es significativamente mayor que el del grupo de control. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Analysis of clinical significance and prognostic impact of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia / 中华血液学杂志

Objective: This study aimed to investigate the clinical and prognostic significance of TET2 single nucleotide polymorphism I1762V in patients with acute myeloid leukemia (AML) . Methods: The high-throughput sequencing method was used to sequence 58 hematological tumor-related genes in bone marrow samples from 413 patients with AML. TET2 I1762V and other somatic mutations were annotated and compared with patients' clinical information and prognosis. Results: I1762V was found in 154 patients with AML, which was significantly different from the general population in NyuWa Chinese Population Variant Database (χ(2)=72.4, P<0.001) . I1762V was not related to sex, age, and karyotype of patients with AML (P>0.05) . Patients with I1762V had a significantly higher proportion of NPM1 and KIT gene mutations than others (P<0.001) . NPM1 and KIT mutations were mutually exclusive. The survival analysis results revealed that the overall survival (OS) and progression-free survival (PFS) of patients with AML with I1762V were significantly greater than those of wild-type patients (HR=0.57, P=0.030; HR=0.55, P=0.020) , whereas the OS and PFS in patients with AML with DNMT3A mutation (with or without I1762V mutation) were lower than those of wild-type patients (HR=1.79, P=0.030; HR=1.74, P=0.040) . Conclusion: TET2 SNP I1762V has been linked to AML. I1762V is a prognostic factor of patients with AML, which can be used to guide the treatment and evaluate the prognosis of AML.

Changes in liver function of Tibetans with different BMI during the early stage of migration to plain / 中国学校卫生

Objective@#To explore the changes in liver function of Tibetan youth living in plateau with different body mass index (BMI) during the early stage of migration to the plain, and to provide scientific basis for high attitude de adaptation.@*Methods@#A total of 3 035 Tibetan youth who firstly migrated to the plain (Shaanxi) from the plateau (Tibet) were selected as the research subjects, and were screened for symptoms of plateau de adaptation. Participants were divided into four groups: underweight, normal weight, overweight and obese, and received liver function test on the 3rd, 6th, 9th dayafter migration, respectively. Chi square test was used to detect the abnormal rate of liver function indicators among each group, and binary Logistic regression analysis was used to explore the relationship between BMI and abnormal liver function indicators.@*Results@#The alanine aminotransferase(ALT), Aspartate aminotransferase(AST), γ glutamyl transpeptidase (GGT) of overweight Tibetan male and obese Tibetan male and female adolescents, the total bile acid (TBA) of overweight Tibetan male and obese Tibetan female were higher than those of the normal weight group at the early stage of de adaptation( P <0.05). With the de adaptation for 3, 6, 9 days, the indexes showed an overall upward trend, including: direct bilirubin (DBIL) in overweight male and female adolescents, total protein (TP) and globulose (GLOB) in obese female adolescents( P <0.05). The abnormal rate of overweight group (male ALT: 13.9%), obesity group (male and female ALT, GGT: 34.3%, 26.7%, 11.4%, 13.3%; female AST:10.0%) was significantly higher than that in underweight (2.8%, 3.5%, 0, 1.0%, 1.5%) and normal group(3.5%, 3.4%, 0.9%, 3.6%, 4.1%)( χ 2=48.07, 20.55, 20.55, 17.93, 10.23 , P <0.05). Binary Logistic regression analysis showed that after adjusting for age and gender, overweight was positively correlated with abnormal ALT( OR=2.10, 95%CI =1.20-3.62). Obesity was positively correlated with abnormal ALT( OR=5.50, 95%CI =4.23-7.40) and GGT( OR=4.10, 95%CI =2.03-6.74)( P <0.05).@*Conclusion@#During the early stage of migration to the plain among Tibetan youth living on the plateau, changes in liver function indicators are related to BMI. Overweight and obese Tibetans have a higher abnormal rate of liver damage indicators. It is suggested that individuals with high risk of obesity should undergo health examination and medical supervision when migrates from plateau to plain.

Strategy Optimization and Clinical Analyze of Multiple Nucleotide Polymorphism Analysis in the Chimerism Detection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

AbstractObjective: To investigate the sample selection, result correction and clinical application value of multi nucleotide polymorphism chimerism detection method based on Next-generation sequencing.@*METHODS@#The chimerism samples from November 2018 to June 2020 were collected, and Pearson correlation coefficient (r) was used to analyze the consistency of bone marrow and peripheral blood results detected by MNPseq; according to the different information integrity before transplantation, the calibration model was constructed to analyze the correction value of the micro chimerism results in each model; the clinical results were retrospectively analyzed to verify the reliability and practicability of chimerism results correction and the clinical value of MNPseq method.@*RESULTS@#The results of bone marrow and peripheral blood chimerism detected by MNPseq method were consistent with each other and showed significant correlation (r=0.985, P<0.01). The three groups of calibration models were constructed according to different pre-transplant information. For the no donor and pre-transplant patients information group, the correction value was 1%; while for the group with pre-transplant patients and without donor information, 0.61% of the chimerism rate and 13 heterotopic points were used as the correction value; 0.26% of the chimerism rate and 21.57% of the heterotopic points were used as the correction value for the group with pre-transplantation patients and donor information. After correction, the number of the patients with incomplete chimerism decreased from 276 (74.19%) to 141 (37.91%) (P<0.01). Among 18 (18/141, 12.77%) patients with incomplete chimerism, the results of MNPseq in the patients were 25-39 days earlier than those in STR and flow MRD, and the result showed statistical significance.@*CONCLUSION@#MNPseq method can be used to monitor chimerism with peripheral blood instead of bone marrow samples, and the results can be corrected to detect the changes of graft status in vivo in a more timely manner.

Protective effects of Baicalin injection on severe acute pancreatitis through regulating follistatin-like-1 signaling pathway by down-regulating miR-429 expression in mice

Abstract In China, Scutellaria is used for treating inflammatory-related diseases. Baicalin is the main active component of Scutellaria and has protective effects on acute pancreatitis. However, the mechanism of Baicalin is still unclear. In this study, the protective effects of baicalin on acute pancreatitis induced by taurocholate and its mechanism are investigated. In this study, mice were randomly divided into three groups: sham operation, model, and treatment groups. Acute pancreatitis in mice was induced by intraperitoneal injection of taurocholate (35 mg/kg). The treatment group was given baicalin (100 mg/kg) 2 h before acute pancreatitis induction. The mRNA expression levels of miR-429, nuclear factor kappa B65(NF-kB65), toll-like receptor 4(TLR4), TNF receptor associated factor6 (TRAF6), NF-kappa-B inhibitor(IkB), Follistatin-like 1 (FSTL1), and interleukin-1 receptor-associated kinase (IRAK) in the liver tissues 24 h after intraperitoneal injection were detected by RT-PCR. Then, the expression levels of NF-kB65, p-NF-κB65, TLR4, TRAF6, IkB, FSTL1, IRAK, p- IRAK, and p- IkB-а proteins were detected by Western blot. IL-6, TNF-α and IL-1 ß in plasma were measured by ELISA, and histopathological changes in the pancreases of the mice were observed. The results showed that after baicalin treatment, miR-429 expression in the pancreatic tissues and the expression levels of NF-kB65, TLR4, TRAF6, p-IkB-а, FSTL1, and p-IRAK decreased. Similarly, pancreatic myeloperoxidase (MPO) activity and the plasma levels of IL-6, TNF-а, IL-12, IL-1ß1, endotoxin, serum amylase, and lipase were reduced. Thus, the pancreatic injury induced by taurocholate was alleviated. The present study indicates that pretreatment with Baicalin can alleviate acute pancreatic injury induced by taurocholate in mice. The mechanism may be associated with the decreased miR-429 expression, reduced FSTL1 signaling pathway activity, TLR4 and TLR4/MyD88 signaling pathway inhibition, and reduced pancreatic inflammation. FSTL1 is the regulatory target for miR-429

Dietary factors associated with overweight and obesity in primary school students in Shenyang / 中国学校卫生

Objective@#To understand the prevalence of overweight and obesity, dietary habits and main food intake frequency among primary school students in Shenyang, so as to provide a reference for exploring the effect of diet related factors on the development of overweight and obesity in children.@*Methods@#A total of 2 041 students from two primary schools in a certain district of Shenyang were selected by convenience sampling in May 2017, with height and weight measured, meanwhile the questionnaire survey regarding dietary habits and the frequency of main food intake were administered.@*Results@#The rates of overweight and obesity were 18.4% and 22.1% respectively, and the rate of overweight and obesity in boys (21.0%，27.8%) were significantly higher than that in girls (15.8%,16.2%)(χ 2=22.45,53.40，P<0.01). The results of univariate analysis showed that frequency of eating breakfast, eating speed, appetite, picky eaters or not, and the frequency of fruit, seafood and canned food intake were associated with overweight and obesity in primary school students (χ 2=7.67，97.92，229.70，95.88，6.40，6.58，7.96，P<0.05). Multivariate Logistic regression analysis showed that slow eating speed (OR=0.46, 95%CI=0.29-0.69) and normal eating speed (OR=0.47, 95%CI=0.32-0.69) were associated with lower rates of overweight and obesity; good appetite (OR=43.73, 95%CI=5.88-325.36) was associated with higher rates of overweight and obesity in primary school students (P<0.01).@*Conclusion@#The detection rate of overweight and obesity is relatively high among primary school students in Shenyang, and the rate of obesity is already higher than that of overweight; The frequency of common food intake has little impact on the development of overweight and obesity in primary school students, but fast eating speed and good appetite are the risks of overweight and obesity among them.

Sarcopenia predicts prognosis of patients with renal cell carcinoma: A systematic review and meta-analysis

ABSTRACT Sarcopenia, a concept reflecting the loss of skeletal muscle mass, was reported to be associated with the prognosis of several tumors. However, the prognostic value of sarcopenia in patients with renal cancer remains unclear. We carried out this metaanalysis and systematic review to evaluate the prognostic value of sarcopenia in patients with renal cell carcinomas. We comprehensively searched PubMed, Embase, and Cochrane Library from inception to December 2018. Hazard ratio (HR) and 95% confidence interval (CI) were pooled together. A total of 5 studies consisting of 771 patients were enrolled in this quantitative analysis, 347 (45.0%) of which had sarcopenia. Patients with sarcopenia had a worse OS compared with those without sarcopenia (HR=1.76; 95%CI, 1.35-2.31; P <0.001). In the subgroup of patients with localized and advanced/metastatic diseases, sarcopenia was also associated with poor OS (HR=1.48, P=0.039; HR=2.14, P <0.001; respectively). With a limited sample size, we did not observe difference of PFS between two groups (HR=1.56, 95% CI, 0.69-3.50, P=0.282). In the present meta-analysis, we observed that patients with sarcopenia had a worse OS compared with those without sarcopenia in RCC. Larger, preferably prospective studies, are needed to confirm and update our findings.

Overexpression of long noncoding RNA PTPRG-AS1 is associated with poor prognosis in epithelial ovarian cancer

SUMMARY OBJECTIVE Long noncoding RNAs (lncRNAs) have been shown to play a critical role in tumor progression. Abnormal expression of LncRNA PTPRG antisense RNA 1 (PTPRG-AS1) has been reported in several tumors. Hence, we aimed to determine the expression and clinical significance of PTPRG-AS1 in epithelial ovarian cancer (EOC) patients. METHODS The expressions of PTPRG-AS1 were assessed in 184 pairs of EOC tumor specimens and adjacent normal tissues. The levels of target lncRNAs and GAPDH were examined using standard SYBR-Green methods. The relationships between the expressions of PTPRG-AS1 and the clinicopathological features were analyzed using the chi-square test. Multivariate analysis using the Cox proportional hazards model was performed to assess the prognostic value of PTPRG-AS1 in EOC patients. RESULTS We confirmed that the expressions of PTPRG-AS1 were distinctly higher in the EOC tissue compared with the adjacent non-tumor specimens (p < 0.01). Higher levels of PTPRG-AS1 in EOC patients were associated with advanced FIGO stage (p = 0.005), grade (p = 0.006), and distant metastasis (p = 0.005). Survival analyses revealed that patients with high expressions of PTPRG-AS1 had a distinctly decreased overall survival (p = 0.0029) and disease-free survival (p = 0.0009) compared with those with low expressions of PTPRG-AS1. Multivariate assays indicated that PTPRG-AS1 expression was an independent prognostic factor for both overall survival and disease-free survival in EOC (Both p < 0.05). CONCLUSIONS Our study suggests that PTPRG-AS1 may serve as a novel prognostic biomarker for EOC patients.

RESUMO OBJETIVO Sabe-se que RNAs longos não codificantes (lncRNAs) desempenham um papel crítico na progressão tumoral. A expressão anormal do RNA 1 anti-senso LncRNA PTPRG (PTPRG-AS1) já foi relatada em diversos tumores. Assim, buscamos determinar a expressão e significância clínica do PTPRG-AS1 em pacientes com câncer de ovário epitelial (COE). METODOLOGIA As expressões do PTPRG-AS1 foram avaliadas em 184 pares de amostras tumorais de COE e tecidos normais adjacentes. Os níveis de lncRNAs e GAPDH alvo foram examinados usando o método padrão de SYBR Green. As relações entre as expressões do PTPRG-AS1 e as características clínico-patológicas foram analisadas através do teste qui-quadrado. Uma análise multivariada utilizando o modelo de riscos proporcionais de Cox foi realizada para avaliar o valor prognóstico do PTPRG-AS1 em pacientes com COE. RESULTADOS Constatou-se que as expressões do PTPRG-AS1 foram nitidamente maiores nos tecidos de COE em relação aos espécimes adjacentes não tumorosos (p<0,01). Níveis mais elevados do PTPRG-AS1 em pacientes com COE foram associados a um estágio avançado de FIGO (p = 0,005), grau (p = 0,006) e metástases à distância (p = 0,005). As análises de sobrevida revelaram que pacientes com expressões elevadas do PTPRG-AS1 tiveram uma diminuição significativa da sobrevida global (p = 0,0029) e da sobrevida livre de doença (p = 0,0009) em relação àqueles com baixas expressões do PTPRG-AS1. As análises multivariadas indicaram que a expressão do PTPRG-AS1 foi um fator de prognóstico independente tanto para a sobrevida global quanto para a sobrevida livre de doença em pacientes com EOC (p < 0,05). CONCLUSÃO Nosso estudo sugere que o PTPRG-AS1 pode ser um novo biomarcador prognóstico para pacientes com COE.

Down-regulated PTTG1 expression promotes the senescence of human prostate cancer LNCaP-AI / 中华男科学杂志

Objective@#To investigate the effect of the down-regulated expression of pituitary tumor-transforming gene 1 (PTTG1) on the senescence of human castration-resistant prostate cancer LNCaP-AI cells.@*METHODS@#Human castration-resistant prostate cancer LNCaP-AI cells were induced in vitro and transfected with siRNA targeting PTTG1 (the siRNA-PTTG1 group), the reagent lip3000 only (the mock group) or siRNA negative control vector (the NC group). All the cells were cultured in fetal bovine serum (FBS) or charcoal-stripped bovine serum (CSS) and counted with the cell counting chamber. The senescence characteristics of the transfected LNCaP-AI cells were examined by senescence-associated β-galactosidase (SA-β-Gal) staining, and the expressions of the senescence-related β-galactosidase-1-like proteins (Glb1), the cyclin-dependent kinase inhibitors p-21CIP1 and p-27Kip1, and the chromatin-regulating heterochromatin protein 1γ (HP1γ) were detected by Western blot.@*RESULTS@#The expression of PTTG1 in the human prostate cancer LNCaP-AI cells was significantly reduced in the siRNA-PTTG1 group compared with those in the mock and NC groups (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05). Culture with FBS markedly increased while that with CSS decreased the number of LNCaP-AI cells transfected with siRNA, but both FBS and CSS enhanced the proliferation of the LNCaP-AI cells in the mock and NC groups. SA-β-Gal staining revealed that reducing the expression of PTTG1 induced a remarkably higher positive rate of the LNCaP-AI cells in the siRNA-PTTG1 than in the mock and NC groups (［63.5 ± 2.35］% vs ［11.3 ± 1.24］% and ［12.4 ± 1.15］%, P < 0.05). The siRNA-PTTG1 group, in comparison with the mock and NC groups, showed a significantly down-regulated expression of PTTG1 (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05), but up-regulated expressions of p-21CIP1 (0.32 ± 0.03 vs 0.20 ± 0.02 and 0.21 ± 0.03, P < 0.05), p-27Kip1 (0.38 ± 0.02 vs 0.20 ± 0.03 and 0.22 ± 0.01, P < 0.05), Glb1 (0.24 ± 0.01 vs 0.13 ± 0.01 and 0.15 ± 0.01, P < 0.05), and HP1γ (0.41 ± 0.01 vs 0.26 ± 0.01 and 0.27 ± 0.02, P < 0.05) in the LNCaP-AI cells.@*CONCLUSIONS@#Down-regulated expression of PTTG1 induces senescence of human castration-resistant prostate cancer LNCaP-AI cells.

Magnetic resonance imaging of the zone of calcified cartilage in the knee joint using 3-dimensional ultrashort echo time cones sequences / 中华医学杂志(英文版)

BACKGROUND@#The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated the feasibility of direct imaging of the ZCC in both cadaveric whole knee specimens and in vivo healthy knees using a 3-dimensional ultrashort echo time cones (3D UTE-Cones) sequence on a clinical 3T scanner.@*METHODS@#In all, 12 cadaveric knee joints and 10 in vivo healthy were collected. At a 3T MR scanner with an 8-channel knee coil, a fat-saturated 3D dual-echo UTE-Cones sequence was used to image the ZCC, following with a short rectangular pulse excitation and 3D spiral sampling with conical view ordering. The regions of interests (ROIs) were delineated by a blinded observer. Single-component T2* and T2 values were calculated from fat-saturated 3D dual-echo UTE-Cones and a Carr-Purcell-Meiboom-Gill (T2 CPMG) data using a semi-automated MATLAB code.@*RESULTS@#The single-exponential fitting curve of ZCC was accurately obtained with R2 of 0.989. For keen joint samples, the ZCC has a short T2* ranging from 0.62 to 2.55 ms, with the mean ± standard deviation (SD) of 1.49 ± 0.66 ms, and with 95% confidence intervals (CI) of 1.20-1.78 ms. For volunteers, the short T2* ranges from 0.93 to 3.52 ms, with the mean ± SD of 2.09 ± 0.56 ms, and the 95% CI is 1.43 to 2.74 ms in ZCC.@*CONCLUSIONS@#The high-resolution 3D UTE-Cones sequence might be used to directly image ZCC in the human knee joint on a clinical 3T scanner with a scan time of more than 10 min. Using this non-invasive technique, the T2* relaxation time of the ZCC can be further detected.

Cytotoxic effect of in vitro expanded NK cell-carrying oncolytic reovirus on colorectal cancer cells / 中国肿瘤生物治疗杂志

@# Objective: To evaluate whether human NK cells expanded in vitro can be used as carrier cells of reovirus and to investigate its clinical application value. Methods: Expansion of human NK cells in vitro, and flow cytometry was used to analyse the purity of CD3-CD56+ cells. Expanded NK cells were loaded with reovirus and observed by confocal microscopy, to determining the location of reovirus on NK cells. CCK-8 assay was used to detect reovirus-induced oncolysis of expanded NK cells carrying reovirus (Reo-NK) to tumor cells in the presence of neutralizing antibodies; Real-time fluorescence quantitative PCR was used to assess the relative expression of viral RNA in tumor cells. Cytotoxicity assay were performed to detect Reo-NK cells against KRAS mutant (DLD-1) and KRAS wild type (CaCo-2, HT29) colorectal cancer cell lines, ELISA matched paired antibodies assay was performed to measure the perforin level released by NK cells. Results: Confocal microscopy demonstrated that NK cells retained reovirus on the surface. Expanded NK cells could delivery reovirus to tumor cells in the presence of neutralizing antibodies, and the reovirus after delivery still had significant oncolytic activity (P<0.01); Corresponding qPCR result displayed that the expression of viral RNA in tumor cells significantly increased over time (P<0.01). Compared with NK group, Reo-NK group evidently enhanced the cytotoxicity on colorectal cancer cell lines with both KRAS gene mutant and wild (all P<0.05), and significantly increased the release of perforin (all P<0.05). Conclusion: In vitro expanded NK cells provide a convincing cell carrier for reovirus, while reovirus enhances the cytotoxicity of NK cells, and the combination of the two show a stronger killing effect on colorectal cancer cells，that has important clinical application value.

An investigation on health risk behaviors among high school students in Jiangxi province / 中国学校卫生

Objective@#To determine health risk behaviors related to accidental injury of adolescent in Jiangxi province,and to provide a peference for taking targeted measures to prevent the occurence of adolescent’s risk behaviors. @*Methods@#By using the cluster stratified sampling, students of grade one and grade two from 10 classes in 5 middle schools in Nanchang city and from 1 middle school in Wuyuan county were selected. Health risk behaviors were investigated through questionnaire survey and were compared within the two areas.@*Results@#Regarding to safety, the rates of never or rarely wearing a helmet when riding a bicycle during the past 12 months, never or rarely wearing a seat belt, text or Email while driving a vehicle and in a physical fight were very high. In Wuyuan county, 35.2% of the students have ever tried cigarette smoking, 51.5% of the students have had at least one drink of alcohol, 4.0% of the students have ever had sexual intercourse, 32.7% of the students describe their weight as slightly or very overweight, 49.1% of the students trying to lose weight. After standardized, the rate of health risk behaviors in Nanchang city was higher than that in Wuyuan county.@*Conclusion@#here are more healthrisk behaviors found among middle school students in Nanchang than in Wuyuan county.The targeted measures should be taken to develop healthy behavior habits of the students to effectively reduce its occurence.

Vaccarin hastens wound healing by promoting angiogenesis via activation of MAPK/ERK and PI3K/AKT signaling pathways in vivo

Abstract Purpose To explore the potential role and unclear molecular mechanisms of vaccarin in wound healing. Methods Rats' skin excision model to study the effects of vaccarin on wound healing in vivo . Hematoxylin and eosin staining was performed to evaluate Histopathologic characteristics. Immunohistochemistry was employed to assess the effects of vaccarin in accelerating angiogenesis. Western blot was used to evaluate relative protein expressed levels. Results Vaccarin could significantly promote wound healing and endothelial cells and fibroblasts proliferation in the wound site. Immunohistochemistry and Western blot studies showed that the nodal proteins and receptor (bFGFR) related to angiogenesis signaling pathway were activated, and the microvascular density in the wound site was markedly higher than that in the control group. Conclusions The present study was the first to demonstrate that vaccarin is able to induce angiogenesis and accelerate wound healing in vivo by increasing expressions of p-Akt, p-Erk and p-bFGFR. This process is mediated by MAPK/ERK and PI3K/AKT signaling pathways.

Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre-clinical animal models

Abstract Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.

Qualitative characterization of flavonoids in Scutellariae Radix by using PREC-IDA-EPI / 中国中药杂志

Flavonoids are the most abundant constituents and induce these the rapeutic effects against inflammation, gastrointestinal infections, cardiovascular diseases, and respiratory. Most of these flavonoids have low content in Scutellarie Radix. It was difficult to detect some minor compounds by using LC-MS method with full scan. Based on the review of flavonoids that had been extracted from Scutellariae Radix, a method with PREC-IDA-EPI technique was developed and applied to Scutellariae Radix by using UPLC-MS/MS. A total of 97 flavonoids were identified, including 29 aglycones and 68 -glycosides. This study laid the foundation for pharmacodynamicss of Scutellariae Radix.It is believed that an individual detection scheme based on the PREC-IDA-EPI technique could be used to identify unknown compounds.

Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus / 中国中药杂志

To study the effect and underlying mechanism of Mahuang Tang against influenza A virus ， the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods， and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER)， median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4， TLR7， MyD88 and TRAF6 in MDCK cells at 24， 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92，1.59 g·L⁻¹ respectively， the TI values were 12.53， 38.78 respectively， and when the concentration of Mahuang Tang was 5.00 g·L⁻¹， ER values were 50.21%， 98.41% respectively， showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile， as compared with the virus group， the virus load was significantly inhibited in Mahuang Tang groups， and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4， TLR7，MyD88 and TRAF6 at 24， 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.