Background Interleukin-4 (IL4) is one of the most important cytokines involved in a variety of allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified an association bet...Background Interleukin-4 (IL4) is one of the most important cytokines involved in a variety of allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified an association between the gene polymorphisms of IL4 and interleukin-4 receptor (IL4R) and asthma in different populations. However, these studies have been inconsistent and inconclusive. The aim of this study was to investigate the association between the single nucleotide polymorphism (SNP) of IL-4, IL-4R and asthma risk in case-controlled studies using meta-analysis. Method A genetic model-free approach was used to perform the meta-analysis. Asthma (atopy status nondefined), nonatopic and atopic asthma subgroups were separately analyzed. Next, the ethnic subgroup was analyzed. Heterogeneity and publication bias were also explored. Results Only two polymorphisms of IL4 (rs2243250 and rs2070874) and four polymorphisms of IL4R (rs1801275, rs1805011, rs1805010, and rs1805015) were included in the meta-analysis. Polymorphisms rs2243250 and rs2070874 of IL-4 and rs1801275 and rs1805011 of IL4R were associated with asthma. The overall odds ratio (OR) of rs2243250 in the CC versus TT+TC genotypes was 0.84 (95% CI: 0.75-0.94), and the Z-test for the overall effect was 3.0 (P=0.003). We obtained significant results from this polymorphism in the Caucasian ethnicity and adult groups. However, the overall OR of rs1801275 for the GG+AG versus AA genotype was 1.16 (95% CI: 1.00-1.35), and the Z-test for the overall effect was 1.87 (P=0.06). Moreover, significant results were only obtained from the sub-group analysis in Asians (P=0.02). In the rs1805011 polymorphism of IL4R, the overall OR for the CC +AC versus AA genotypes was 0.39 (95% CI: 0.16-0.95), and the Z-test for the overall effect was 2.08 (P=0.04). Conclusions Both the IL4 and IL4R polymorphisms were associated with asthma. The rs2243250 polymorphism of IL4 was more important in the white and adult groups展开更多
BACKGROUND Epstein-Barr virus(EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma(GCLS).Clinicopathological studies have indicated a better p...BACKGROUND Epstein-Barr virus(EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma(GCLS).Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas.Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.CASE SUMMARY We present two GCLS cases subjected to endoscopic submucosal dissection(ESD)for a definitive diagnosis.A protruded gastric lesion was identified by routine endoscopic examination,but forceps biopsy showed no atypical cells before ESD.The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa.The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma.Accordingly,additional gastrectomy was recommended to obtain a complete cure.One patient underwent additional distal gastrectomy with lymph node dissection,but the other was refused because of cardiovascular complications.Both patients remained in remission for more than half a year.EBV positivity was determined by EBV-encoded RNA in situ hybridization.We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.CONCLUSION Submucosa-invasive GCLS could be dissected using ESD,and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required.Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.展开更多
AIM:Hepatitis C virus(HCV)infection is very common among end-stage kidney disease patients on hemodialysis,but its natural history is not known. METHODS:In this study,189 dialysis patients(case) positive for HCV antib...AIM:Hepatitis C virus(HCV)infection is very common among end-stage kidney disease patients on hemodialysis,but its natural history is not known. METHODS:In this study,189 dialysis patients(case) positive for HCV antibodies who were followed up for more than 4 years were compared with twice as many sex/age matched controls with chronic hepatitis C who were diagnosed in the same month as the case and followed up for comparable periods.The longest follow-up was 23 years in dialysis cases. The disease activities were graded into'asymptomatic'if ALT was less than 40(35 in cases)IU/L,'low activities'if ALT was 40(35)-79 IU/L,and'high activities'if ALT was above 80 IU/L during the last or latest 4 year period. RESULTS:All 25 dialysis cases who were followed up for more than 15 years were asymptomatic and 15 of them were negative for HCV RNA.Of the 50 controls followed up for more than 15 years,34 had high activities,and none deared HCV RNA.There were 60 controls who were asymptomatic, but they were all positive for HCV RNA,while 22.3% of asymptomatic dialysis cases were RNA negative.No dialysis patients with chronic hepatitis C progressed to cirrhosis, whereas the disease progressed to cirrhosis in more than one quarter of the controls.These differences were highly significant(P<0.0001). CONCLUSION:Chronic hepatitic C among hemodialysis patients is mild in disease activity,and is not progressive, perhaps due to immunological abnormalities in these patients. Hepatic C virus is frequently cleared in asymptomatic dialysis patients during a long course.A possible mechanism for viral clearance is viral particle destruction on the surface of the dialyzer membrane.展开更多
Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The a...Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^+CD25^+ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4+ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.展开更多
Background Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. B...Background Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C〉T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated. Methods A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G〉A(rs1957860) 5' of the transcription start site and 6007C〉T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed. Results A significant statistical difference in genotype of 6007C〉T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P=0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P=0.014, OR=1.57). A significant difference was also observed between the 6007C〉T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G〉A polymorphism and OPLL occurrence. Conclusions The T allele in the 6007C〉T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C〉T genotypes have a genetic susceptibility to OPLL and more extensi展开更多
文摘Background Interleukin-4 (IL4) is one of the most important cytokines involved in a variety of allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified an association between the gene polymorphisms of IL4 and interleukin-4 receptor (IL4R) and asthma in different populations. However, these studies have been inconsistent and inconclusive. The aim of this study was to investigate the association between the single nucleotide polymorphism (SNP) of IL-4, IL-4R and asthma risk in case-controlled studies using meta-analysis. Method A genetic model-free approach was used to perform the meta-analysis. Asthma (atopy status nondefined), nonatopic and atopic asthma subgroups were separately analyzed. Next, the ethnic subgroup was analyzed. Heterogeneity and publication bias were also explored. Results Only two polymorphisms of IL4 (rs2243250 and rs2070874) and four polymorphisms of IL4R (rs1801275, rs1805011, rs1805010, and rs1805015) were included in the meta-analysis. Polymorphisms rs2243250 and rs2070874 of IL-4 and rs1801275 and rs1805011 of IL4R were associated with asthma. The overall odds ratio (OR) of rs2243250 in the CC versus TT+TC genotypes was 0.84 (95% CI: 0.75-0.94), and the Z-test for the overall effect was 3.0 (P=0.003). We obtained significant results from this polymorphism in the Caucasian ethnicity and adult groups. However, the overall OR of rs1801275 for the GG+AG versus AA genotype was 1.16 (95% CI: 1.00-1.35), and the Z-test for the overall effect was 1.87 (P=0.06). Moreover, significant results were only obtained from the sub-group analysis in Asians (P=0.02). In the rs1805011 polymorphism of IL4R, the overall OR for the CC +AC versus AA genotypes was 0.39 (95% CI: 0.16-0.95), and the Z-test for the overall effect was 2.08 (P=0.04). Conclusions Both the IL4 and IL4R polymorphisms were associated with asthma. The rs2243250 polymorphism of IL4 was more important in the white and adult groups
文摘BACKGROUND Epstein-Barr virus(EBV)-associated carcinoma is a gastric cancer subtype with a morphology characterized by gastric carcinoma with lymphoid stroma(GCLS).Clinicopathological studies have indicated a better prognosis for GCLS than for common gastric carcinomas.Some previous cases of early gastric cancer associated with EBV had been diagnosed by endoscopic resection.CASE SUMMARY We present two GCLS cases subjected to endoscopic submucosal dissection(ESD)for a definitive diagnosis.A protruded gastric lesion was identified by routine endoscopic examination,but forceps biopsy showed no atypical cells before ESD.The resected specimen showed a poorly differentiated adenocarcinoma with lymphoid cells involving the mucosa and submucosa.The final diagnosis was submucosa-invasive poorly differentiated gastric adenocarcinoma.Accordingly,additional gastrectomy was recommended to obtain a complete cure.One patient underwent additional distal gastrectomy with lymph node dissection,but the other was refused because of cardiovascular complications.Both patients remained in remission for more than half a year.EBV positivity was determined by EBV-encoded RNA in situ hybridization.We also conducted a literature review of cases of early gastric cancer associated with EBV that had been diagnosed by ESD.CONCLUSION Submucosa-invasive GCLS could be dissected using ESD,and EBV positivity should be subsequently assessed to determine whether or not any additional curative surgery is required.Further prospective investigations on the prevalence of lymph node metastasis in EBV-associated carcinoma should be performed to expand the indications for endoscopic resection.
文摘AIM:Hepatitis C virus(HCV)infection is very common among end-stage kidney disease patients on hemodialysis,but its natural history is not known. METHODS:In this study,189 dialysis patients(case) positive for HCV antibodies who were followed up for more than 4 years were compared with twice as many sex/age matched controls with chronic hepatitis C who were diagnosed in the same month as the case and followed up for comparable periods.The longest follow-up was 23 years in dialysis cases. The disease activities were graded into'asymptomatic'if ALT was less than 40(35 in cases)IU/L,'low activities'if ALT was 40(35)-79 IU/L,and'high activities'if ALT was above 80 IU/L during the last or latest 4 year period. RESULTS:All 25 dialysis cases who were followed up for more than 15 years were asymptomatic and 15 of them were negative for HCV RNA.Of the 50 controls followed up for more than 15 years,34 had high activities,and none deared HCV RNA.There were 60 controls who were asymptomatic, but they were all positive for HCV RNA,while 22.3% of asymptomatic dialysis cases were RNA negative.No dialysis patients with chronic hepatitis C progressed to cirrhosis, whereas the disease progressed to cirrhosis in more than one quarter of the controls.These differences were highly significant(P<0.0001). CONCLUSION:Chronic hepatitic C among hemodialysis patients is mild in disease activity,and is not progressive, perhaps due to immunological abnormalities in these patients. Hepatic C virus is frequently cleared in asymptomatic dialysis patients during a long course.A possible mechanism for viral clearance is viral particle destruction on the surface of the dialyzer membrane.
基金supported by the National Natural Science Foundation of China (No.30330540)the Jiangsu Provincial Fund for Clinical Immunology Key Laboratory (No.200319)the Scientific and Technological Fund to Support Project of Suzhou City (ZS0901)
文摘Objective Age-related increment of the prevalence of CD4^+CD25^+ regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8+ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^+CD25^+ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4+ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.
基金This research was supported by grants from the Basic Research Clinic Foundation of Capital Medical University (No. 2007JL38) and Beijing Municipal Natural Science Foundation (No. 7092028).
文摘Background Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C〉T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated. Methods A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G〉A(rs1957860) 5' of the transcription start site and 6007C〉T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed. Results A significant statistical difference in genotype of 6007C〉T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P=0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P=0.014, OR=1.57). A significant difference was also observed between the 6007C〉T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G〉A polymorphism and OPLL occurrence. Conclusions The T allele in the 6007C〉T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C〉T genotypes have a genetic susceptibility to OPLL and more extensi