Upregulation and biological function of transmembrane protein 119 in osteosarcoma

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.

Relationship between HBeAg seroconversion with genotypes and HBV specific CTL in patients with chronic hepatitis B treated with Adefovir dipivoxil / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL in patients with chronic hepatitis B (CHB) treated with Adefovir dipivoxil.</p><p><b>METHODS</b>Seventy CHB patients had positive HBV DNA (HBV DNA > or = 1 x 10(4) copy/ml), 45 cases had positive HBeAg, of whom 23 cases (51. 11%) had genotype B, 22 cases (48.89%) had genotype C. ALT > 2 x upper limit of normal value (ULN), human leukocyte antigen (HLA)-A(n) positive, patients were treated with Adefovir dipivoxil (commercial name is Mingzheng, Zhengda Tianjing Pharmaceutical Company), 10 mg, orally, once a day. After treatment for 12 months, observe relationship between HBeAg seroconversion with HBV genotypes and HBV specific CTL.</p><p><b>RESULTS</b>After treatment with Adefovir dipivoxil for 12 months, HBV specific CTL (0.68% +/- 0.11%) was higher than that before treatment (0.33% +/- 0.11%), t = 8.36 P < 0.001, HBV DNA (3.01 +/- 0.2) log10 copy/ml was lower than that before treatment (6.27 +/- 0.70) log10 copy/ml, t = 12.63 P < 0.001, HBV DNA turned negative (< 500 copy/ml) 43 cases (61.43%), in 45 cases with positive HBeAg, HBeAg turned negative in 13 cases (28.89%), 8 cases had HBeAg seroconversion (17.78%), HBV specific CTL (0.86% +/- 0.05%) of patients with HBeAg seroconversion is higher than (0.61% +/- 0.07%) of patients without HBeAg seroconversion (37 cases, 82.22%) t = 7.88, P < 0.001. In 8 cases with HBeAg seroconversion, 7 cases had genotype B (30.43% of genotype B), 1 cases had genotype C (4.55% of genotype C), chi2 = 5.15, P < 0.05.</p><p><b>CONCLUSION</b>Adefovir dipivoxil can enhance HBV specific cellular immunity of CHB patients. After treatment, occurrence of HBeAg seroconversion is related to increase of HBV specific CTL level and may be related to genotypes.</p>

Influence of adefovir dipivoxil on HBV specific CTL in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the influence of adefovir dipivoxil on HBV specific CTL in patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>10 mg adefovir dipivoxil (Zhengda Tianjing Pharmaceutical Company) was used for CHB patients with positive HBV DNA (HBV DNA > or = 1 x 10(4) copies/ml), ALT > 2 x upper limit of normal value (ULN) and positive human leucocyte antigen (HLA)-A2, orally, once a day for 3 months. Real time fluorescent quantitative PCR was used to determine HBV DNA and flowcytometer was used to determine HBV specific CTL.</p><p><b>RESULTS</b>After treatment with adefovir dipivoxil for 3 months, HBV specific CTL (0.52 +/- 0.11)% was higher than that before treatment (0.34 +/- 0.14)%, t = 6.78 P < 0.01, HBV DNA of 28 cases turned to negative (<1 x 10(3) copies/ml) (62.22%). HBV DNA of 17 cases failed to turn negative 3 months after treatment, but their HBV DNA level was lower [(4. 18 +/- 0.4) log 10 copies/ml] than that before treatment [(6.23 +/- 0.73) log 10 copies/ml], t = 9.99, P < 0.01.</p><p><b>CONCLUSION</b>Adefovir dipivoxil can improve HBV specific cellular immunity in patients CHB.</p>

Study on the association between total plasma homocysteine levels, dietary habits and the risk of gastric cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the relationship between total plasma homocysteine (tHcy) levels, dietary habits and susceptibility of gastric cancer (CGC) in Yangzhong and Yixing cities, the two high GC risk areas in Jiangsu province.</p><p><b>METHODS</b>A population-based case-control study was conducted including 391 histologically-confirmed adenocarcinoma GC cases and 608 age and sex frequency-matched cancer-free controls. The plasma tHcy concentration was measured by enzymatic biochemical assay of homocysteine on microtiter plates, using crude lysate containing recombinant methionine 7-lyase. The relationship between different tHcy levels and risk of GC was analyzed and factors as vegetables and fruits intake, smoking and drinking status were also evaluated together with tHey levels on the risk of GC.</p><p><b>RESULTS</b>The average tHcy levels in GC cases were significantly higher than that in controls (P = 0.002). In addition, according to the quartile levels (7.9, 10.1, 13.7 micromol/L) in the controls, the risks of GC had an increase of 67% (adjusted OR = 1.67, 95% CI: 1.12-2.48), 98% (adjusted OR = 1.98, 95% CI: 1.33-2.94) and 112% (adjusted OR = 2.12, 95% CI: 1.44-3.15) compared to the lowest quartile of tHcy (< or = 7.9 micromol/L), respectively while the increasing trend was significantly noticed (chi2 = 15.78, P < 0.001). The increase of vegetables and fruits intake could decrease the risk of GC. Results from crossover analyses indicated that subjects with less vegetables and fruits intake or both smoking drinking together with plasma tHcy >15.0 micromol/L could increase the GC risk, when compared to the effect on GC risk of each factor.</p><p><b>CONCLUSION</b>These findings supported the hypothesis that the high level of plasma tHcy and the badness dietary habits were associated to the increased risk of GC. Further larger scale and genetics involved studies on the environment and genetic factors were needed to confirm our findings.</p>

The genetic polymorphism of HLA-DQA1 and HLA-DQB1 genes of Chinese Han population in Jiangsu area is studied by PCR-sequence-based typing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the polymorphism of HLA-DQA1 and DQB1 genes of Han population in Jiangsu of China.</p><p><b>METHODS</b>The alleles and haplotypes frequencies of HLA-DQA1 and DQB1 genes in 100 unrelated healthy individuals were analyzed by using polymerase chain reaction-sequence-based typing (PCR-SBT).</p><p><b>RESULTS</b>Among the 7 DQA1 alleles detected, the most common allele was DQA1*0301/02/03 with a frequency of 29.5%, which was followed by DQA1*0501, DQA1*0102 and DQA1*0201 with frequencies of 18.5%, 17.0% and 12.5%, respectively. Of the 13 DQB1 alleles detected, DQB1*0201/02 allele (21.5%) was the most frequent allele, followed by DQB1*0301/09 (14.5%), DQB1*0303 (13.5%) and DQB1*0603 (11.5%). The most common DQA1 vs DQB1 haplotype was DQA1*0301/02/03 vs DQB1*0303 with a frequency of 12.5%, which was followed by the DQA1*0201-DQB1*0201/02 (10.5%),DQA1*0501-DQB1*0201/02 (9.5%) and DQA1*0501-DQB1*0301/09 (7.0%).</p><p><b>CONCLUSION</b>The distribution of HLA-DQ alleles and haplotypes in Jiangsu Han population shares some genetic characteristics with other population in northern of China, but has its own characteristics. The data will provide useful information for anthropology, organ transplantation and disease association studies.</p>

The association of polymorphisms of CDT1 and GMNN gene with the risk of breast cancer in Chinese women: a case-control analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population.</p><p><b>RESULTS</b>No significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09).</p><p><b>CONCLUSION</b>These findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.</p>

Study on the coinfection of Hantavirus and Orientia tsutsugamushi in tissue cell culture / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the possibility of Hantavirus (HV) and Orientia tsutsugamushi (Ot) coinfection in their hosts.</p><p><b>METHODS</b>HV and Ot were used to infect Vero E6 cells cultured in vitro singly, simultaneously or successively. Genes of HV and Ot were identified in different generation cells with RT-PCR.</p><p><b>RESULTS</b>Five experiment groups of infected Vero E6 cells were tested, the results were as follows: HV and Ot were both positive in infected Vero E6 cells passaged 2 times and the positive rate increased following the passaged times in HV and Ot infection groups, simultaneously or successively. However, in the groups which were infected with HV and Ot separately, the gene of HV or Ot could be detected in infected Vero E6 cells passaged only once and the positive rate increased following the times of the passaged. The positive rate was higher in the singly infected groups than in those infected simultaneously or successively.</p><p><b>CONCLUSION</b>Coinfection of HV and Ot did exist in the hosts while HV and Ot could inhibit each other in the initial infection stage.</p>

Study on hepatitis C virus genotyping in Yixing area, Jiangsu province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the distribution of hepatitis C virus (HCV) genotypes in Yixing, Jiangsu province.</p><p><b>METHODS</b>Genotypes identification on sera samples were obtained from 158 donors who had already been anti-HCV positive through PCR method with type specific primer designed according to the sequence of 5'non-coding region (5'NCR). 5'NCR was also sequenced and compared with published date. Genotypes distribution was investigated in patients with different sex and clinical types of hepatitis C.</p><p><b>RESULTS</b>Of the total 158 patients, 95 were HCV RNA positive in which 80 patients having genotype 1b (80/95; 84.4%), 5 patients having genotype 2(5/95; 5.3%), 5 patients with 1b/2 mixed genotypes (5/ 95; 5.3%) and another 5 patients whose genotype undetermined. The difference on the distribution of HCV genotypes was significant between female and male patients (P < 0.05) but not in different kinds of hepatitis C patients.</p><p><b>CONCLUSION</b>Type 1b was the predominant HCV genotype in Yixing area.</p>