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BACKGROUND: Interleukin-1 is an important pro-inflammatory cytokine that has been documented in the regulation of bone inflammation and bone remodeling. A previous study has demonstrated that interleukin-1α can induce apoptosis while inhibiting osteoblast differentiation in MC3T3-E1 cells. OBJECTIVE: To investigate the role and mechanism of interleukin-1α on osteoclast activation and bone loss in mice. METHODS: (1) Cell test: RAW264.7 cells were either treated with interleukin-1α alone or with receptor activator of nuclear factor-κB ligand (RANKL) for 1 and 4 days. Cell viability was tested by cell counting kit-8 assay. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The mRNA and protein levels of osteoclast-specific genes and genes related to nuclear factor-κB pathway and Wnt/β-catenin pathway were tested by real-time fluorescence quantitative PCR, immunofluorescence staining or western blot. Bone marrow-derived macrophages were either treated with interleukin-1α alone or with RANKL and macrophage colony-stimulating factor for 7 days. The number of multinuclear osteoclasts was detected by tartrate resistant acid phosphatase assay. The protein levels of osteoclast-specific genes were tested by western blot. (2) Animal test: Twenty-four male C57BL/6J mice (6-8 weeks old) were assigned into two groups at random: control group and test group. Mice were subsequently treated with interleukin-1α solution or PBS by intraperitoneal injection twice a week for 5 weeks. Bone tissues from the femurs were performed with micro-computed tomography analysis and hematoxylin-eosin staining, tartrate resistant acid phosphatase, and immunofluorescence analysis. RESULTS AND CONCLUSION: Cell test: Interleukin-1α alone significantly increased RAW264.7 cell proliferation, but stimulated cell differentiation into osteoclasts in combination with RANKL (P < 0.05). Interleukin-1α significantly increased the expression of osteoclast-related markers and the number of tartrate resistant acid phosphatase-positive multinuclear cells in RAW264.7 cells and bone marrow-derived macrophages in the existence of RANKL or RANKL+macrophage colony-stimulating factor (both P < 0.05). Interleukin-1α was found to significantly enhance the nuclear factor-κB and Wnt/beta-catenin signaling in RAW264.7 cells (P < 0.05). Blocking of nuclear factor-κB or Wnt3 signaling not only reversed the activation of nuclear factor-κB and Wnt3 signaling but also weakened the enhanced expression of osteoclast-specific genes induced by interleukin-1α in RAW264.7 cells (P < 0.05). Animal test: interleukin-1α induced bone loss in mice while also upregulating the expression of osteoclast-specific markers, RANK, TRAF6 and p65, and Wnt3 in vivo (P < 0.05). The findings indicate that interleukin-1α can induce osteoclast activation and bone loss by promoting the nuclear factor-κB and Wnt signaling pathways.
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Objective:To investigate the expression of spindle and kinetochore-associated complex subunit 1 (SKA1) gene in clear cell renal cell carcinoma (ccRCC) and its clinical significance.Methods:The venous blood samples of 76 preoperative patients with ccRCC and 24 healthy subjects were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2018. The level of SKA1 in whole blood was detected by real-time fluorescence quantitative PCR, and the relationship between SKA1 level and clinicopathological characteristics was analyzed. SKA1 data were retrieved from Oncomine (v4.5), The Human Protein Atlas (THPA) gene databases, The Cancer Genome Atlas (TCGA) databasec (cBioportal) and Gene Expression Omnibus (GEO). The Kaplan-Meier method was used to perform patients′ survival analysis based on cBioportal ccRCC data, and the survival rates were compared by log-rank method. The relationship between SKA1 expression level and clinicopathological characteristics was analyzed by χ2 test. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of SKA1 mRNA in ccRCC, and enrichment analysis of SKA1 gene was carried out using KOBAS 3.0 online tool. Results:Two studies on the expression level of SKA1 mRNA in ccRCC were retrieved from Oncomine (v4.5) database, and there were 38 samples. The results showed that SKA1 mRNA was highly expressed in ccRCC tissues. Further detection showed that the expression level of SKA1 mRNA in ccRCC tissues was significantly higher than that in normal renal tissues [-2.21(-3.56, -1.59) vs. -3.41(-4.55, -1.65)], and there was a statistically significant difference ( Z=2.282, P=0.022). The analysis of THPA online website showed that SKA1 protein showed obvious moderate staining in ccRCC tissues, while weakly positive or no expression in normal renal tissues. SKA1 was mainly located in the plasma membrane, which was consistent with the results of mRNA analysis. The results of cBioportal showed that the expression level of SKA1 was significantly correlated with AJCC staging ( χ2=21.352, P<0.001), T staging ( χ2=19.967, P<0.001), N staging ( χ2=11.323, P=0.003) and M staging ( χ2=27.248, P<0.001). The relative level of SKA1 in peripheral blood of 76 patients with ccRCC was 0.301±0.147, and 0.162±0.052 in healthy subjects, with a statistically significant difference ( t=7.360, P<0.001). The level of SKA1 was correlated with AJCC staging ( t=2.445, P=0.017) and lymph node metastasis ( t=2.242, P=0.028). The results were consistent with tissue analysis in cBioportal database. Survival analysis showed that in cBioportal database, the expression level of SKA1 mRNA was related to the overall survival rate and disease free survival rate of patients with ccRCC ( χ2=22.440, P<0.001; χ2=23.830, P<0.001). In GEO database, the expression level of SKA1 mRNA was not related to the overall survival rate of patients with ccRCC ( χ2=0.241, P=0.632). The results of ROC analysis in cBioportal database showed that when the cut-off value was -0.944, the sensitivity and specificity of SKA1 mRNA in the diagnosis of ccRCC were 100% and 98.7%. The area under the ROC curve (AUC) was 0.991 (95% CI: 0.972-1.000). The results of ROC analysis of 76 patients with ccRCC showed that when the cut-off value was 0.235, the sensitivity and specificity of peripheral blood SKA1 in the diagnosis of ccRCC were 75.0% and 95.8%, and the AUC was 0.837 (95% CI: 0.761-0.914). KOBAS enrichment analysis showed that SKA1 high expression samples were enriched in gene sets such as chromosomal centromeres, microtubule polymerization and depolymerization regulation and mitotic spindle check-up points. Conclusion:SKA1 is highly expressed in ccRCC tissues, which is obviously related to the prognosis of patients. It can be used as a diagnostic indicator and potential therapeutic target for ccRCC.
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Objective To understand and evaluate the prevalence of myopia and its trend in children and adolescents aged 7-18 years in Han ethnic group in China from 2005 to 2014,and provide evidence for the prevention of myopia.Methods The data of 2005,2010 and 2014 Chinese National Students Constitution and Health Surveys were collected.The children and adolescents with complete detection data of binoculus were selected as study subjects.The sample size of three studies were 233 108,215 319 and 212 743,respectively.The method of curve fitting was used to simulate the myopia detection increase model and analyze the gender and area specific myopia detection increase trends and characteristics from 2005 to 2014.Results The overall myopia detection rate increased gradually in the children and adolescents aged 7 to 18,which was 47.5％ in 2005,55.5％ in 2010 and 57.1％ in 2014,respectively.The increase slowed in 2014.A "parabola" shape of myopia detection increase rate was observed.Myopia detection rate increased with age before puberty and decreased with age after puberty gradually.A "cross phenomenon" of myopia detection increase was observed in boys and girls between urban and rural areas.The increase of myopia detection was mainly in urban students before puberty and in rural students after puberty.The age of myopia prevalence peak has become earlier constantly in children and adolescents aged 7-18 years from 2005 to 2014,which was 13 years old in 2005,12 years old in 2010 and 11 years old in 2014.The increase rate was about 7％.During 2005-2014,the increase rate of myopia detection gradually increased in younger students and tended to zero in older students.Conclusion The detection rate of myopia was still high in children and adolescents in China.The age of myopia prevalence peak has become earlier gradually.
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Objective@#To investigate the characteristics of geographic distribution and change trend of myopia prevalence for children and adolescents aged 7-18 years old from 2005 to 2014, which provides the basis for the prevention of myopia.@*Methods@#Research material was selected from the data of 2005, 2010, and 2014 Chinese National Survey on Students Constitution and Health, including 31 provinces (with the exception of Hong Kong, Macao, and Taiwan). The complete detection data of binoculus in children and adolescents aged 7-18 years old were selected as our research objects. The research objects of three studies were 233 505, 216 474, and 215 160, respectively. We analyzed the characteristics of geographic distribution and change trend of myopia prevalence for children and adolescents aged 7-18 years old in 31 provinces from 2005 to 2014.@*Results@#The overall myopia detection rates in Chinese children and adolescents aged 7 to 18 years old in 31 provinces were 47.4% (111 707/235 505), 55.6% (120 456/216 474), and 57.2% (122 965/215 160) in 2005, 2010 and 2014, respectively. The growth range in this two phases were 8.0 percentage points, and 1.6 percentage points, respectively, and the difference was statistically significant (P<0.05). The detection rate of Myopia was growing quickly from 2005 to 2010 and only three provinces were in the situation of decline state including Tianjin, Hainan, and Ningxia. 90.3 percent (28/31) of provinces were in the situation of growth state and the growth range was 1.3%-22.3%. The growth of myopia was in the situation of slowdown from 2010 to 2014, and 38.7 percent (12/31) of the provinces were in negative growth districts including Hebei, Shanxi, Inner Mongolia, Zhejiang, Fujian, Shandong, Hubei, Guangxi, Guizhou, Tibet, Qianghai, and Xinjiang. The growth range in other provinces was 0.4%-24.7%.@*Conclusion@#The myopia detection rate was at a higher level and growing constantly in China. There was large difference for myopia of children and adolescents among the 31 provinces. However, the overall growth rate of myopia in children and adolescents was in the situation of a relatively low level form 2010 to 2014.
ABSTRACT
Objective To understand and evaluate the prevalence of myopia and its trend in children and adolescents aged 7-18 years in Han ethnic group in China from 2005 to 2014,and provide evidence for the prevention of myopia.Methods The data of 2005,2010 and 2014 Chinese National Students Constitution and Health Surveys were collected.The children and adolescents with complete detection data of binoculus were selected as study subjects.The sample size of three studies were 233 108,215 319 and 212 743,respectively.The method of curve fitting was used to simulate the myopia detection increase model and analyze the gender and area specific myopia detection increase trends and characteristics from 2005 to 2014.Results The overall myopia detection rate increased gradually in the children and adolescents aged 7 to 18,which was 47.5％ in 2005,55.5％ in 2010 and 57.1％ in 2014,respectively.The increase slowed in 2014.A "parabola" shape of myopia detection increase rate was observed.Myopia detection rate increased with age before puberty and decreased with age after puberty gradually.A "cross phenomenon" of myopia detection increase was observed in boys and girls between urban and rural areas.The increase of myopia detection was mainly in urban students before puberty and in rural students after puberty.The age of myopia prevalence peak has become earlier constantly in children and adolescents aged 7-18 years from 2005 to 2014,which was 13 years old in 2005,12 years old in 2010 and 11 years old in 2014.The increase rate was about 7％.During 2005-2014,the increase rate of myopia detection gradually increased in younger students and tended to zero in older students.Conclusion The detection rate of myopia was still high in children and adolescents in China.The age of myopia prevalence peak has become earlier gradually.