Pleiotropic genomic variants at 17q21.31 associated with bone mineral density and body fat mass: a bivariate genome-wide association analysis

Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, {"type":"entrez-nucleotide","attrs":{"text":"NC_000017.11","term_id":"568815581"}}NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10⁻⁹, replication P = 5.75 × 10⁻⁵) at the genome-wide significance level (ɑ = 5.0 × 10⁻⁸), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.Subject terms: Genome-wide association studies, Gene expression profiling     

Inhibition of experimental autoimmune tubulointerstitial nephritis in Brown-Norway rats by (15S)-15-methyl prostaglandin E1. Analysis of the effect of prostaglandin E1 on the induction of the humoral immune response and the elicitation of humorally mediated inflammation.

Brown-Norway (BN) rats develop tubulointerstitial nephritis (TIN) after immunization with bovine tubular basement membrane (TBM) and adjuvants. Daily subcutaneous injections (either on Days 0-7 or Days 0-14) of (15S)-15-methyl prostaglandin E1 (M-PGE1) at a dose of 1 mg/kg/day markedly inhibited or completely abrogated the development of both the acute polymorphonuclear (Day 10) and the subsequent mononuclear (Day 14) inflammatory phases of BN rat TIN. Circulating anti-TBM antibody in Days 0-7 M-PGE1-treated rats was moderately diminished on Day 8 after immunization but not on Day 14. Circulating anti-TBM antibody in Days 0-14 M-PGE1-treated rats was only slightly diminished on Day 14. In experiments to test the effect of M-PGE1 on the elicitation phase of humorally mediated inflammation, M-PGE1 inhibited the acute inflammatory response observed 6 hours after intradermal injection of particulate TBM into TBM-sensitized BN rats. The inflammation in these skin tests was demonstrated by passive transfer experiments to be humorally mediated. The inhibition of acute humorally mediated intradermal inflammation was not attributable to neutropenia, because M-PGE1 caused a significant neutrophilia as demonstrated by peripheral blood smears. Although the inhibition of TIN in Days 0-14 M-PGE1-treated rats may have been due, in part, to dysfunction of the elicitation phase of humorally mediated inflammation, the inhibition of TIN in Days 0-7 M-PGE1-treated rats was more likely secondary to the diminished induction of either humoral or cellular immunity.     

Expression of interleukin-18 by nasopharyngeal carcinoma cells: a factor that possibly initiates the massive leukocyte infiltration

Interleukin-18 (IL-18) is a single-chain cytokine that is produced by various cells. With interleukin-12 (IL-12), it synergistically stimulates activated T cells and natural killer (NK) cells to produce interferon-gamma (IFN-gamma). Nasopharyngeal carcinoma (NPC) is the most common form of nasal and nasopharyngeal malignancy, and in NPC tumor tissues there is an intense leukocyte infiltration comprising predominantly T cells and macrophages. We previously showed an increased expression of IFN-gamma in the infiltrating T cells. To identify the cells that provide IL-12 and IL-18 for stimulating the expression of IFN-gamma in activated T cells, NPC cell lines CNE-2 and HK-1, as well as biopsies obtained from NPC and control individuals, were examined. CNE-2 and HK-1 cells were found to express messenger RNA encoding IL-18, but not IL-12. Secreted IL-18 was detected in the culture supernatant. Addition of a caspase-1 inhibitor decreased the secretion level, indicating that this IL-18 secretion was caspase-1 dependent. Moreover, the in vitro IL-18 production in NPC cell lines correlated with the NPC tumor cells in situ. NPC tumor cells in the biopsies produced IL-18, as detected by immunohistochemistry and immunofluorescent double staining. In contrast, IL-18 expression was not observed in the control biopsies. We suggest that IL-18 secreted by NPC tumor cells plays a role in initiating the leukocyte infiltration process. IL-18 stimulates T cells and NK cells to produce IFN-gamma, which consequently activates macrophages and other immune cells to secrete chemokines to start a leukocyte recruitment cascade.     

社区老年人心理卫生保健模式分析研究

目的研究社区老年人的心理健康状况及其心理卫生保健模式。方法采用心理调查问卷并进行统计分析，结果社区老年人心理健康水平与全国成人相比存在明显差异。结论本研究顾示，社区老年人心理健康问题突出，对此提出相应心理卫生保健模式以期改善老年人心理健康状况。     

慢性乙肝患者血清趋化因子RANTES水平与肝功能生化指标等的相关性研究

Objective To investigate the level of the serum chemokine RANTES and its correlation with serum biochemical indices of liver function test, HBeAg and HBV DNA load in patients with chronic hepatitis B.Methods 144 patients with chronic hepatitis B (observed group) and 18 normal cases (control group) were enrolled in this study. The serum level of chemokine RANTES was detected with an ABC-ELISA assay. Statistical analysis was performed on the software of SPSS13.0. Results The serum chemokine RANTES level in the observed group (3930.12 ng/ml±2856.96) ng/ml was significantly higher than that in the control group (329.46 ng/ml±152.23) ng/ml. The results from the observed group indicated the positive correlation of serum RANTES level with indices of liver function test, including ALT (r=0. 197, P=0.018), AST(r=0.239, P=0.004) and TBil (r=0.316, P=0.001), but did not with PTA (r=-0.078, P=0.357). Neither difference of serum chemokine RANTES level between HBeAg-positive group and HBeAg-negative group nor that between high HBV DNA load group (≥105 copies/ml) and low HBV DNA load group (< 105 copies/ml) were statistically significant (P=0.407 and 0.185, respectively). Conclusions Serum chemokine RANTES level in patients with chronic hepatitis B elevates significantly and is not affected by HBeAg or HBV DNA load. Its positive correlation with indices of liver function test indicates that RANTES might play an important rule in the pathogenesis of chronic hepatitis B.     

急性鸭乙型肝炎病毒感染病毒清除机理研究

目的 :进一步阐明嗜肝病毒自然感染过程中病毒清除机理。方法 :7只 2～ 3月龄成年重庆麻鸭静脉接种 10～ 2 0mlDHBV阳性血清 (5× 10 8～ 1× 10 9genome) ,接种后每周采血检测外周血中DHBVDNA、DHBsAg和特异抗体的产生 ;感染后第10、35天分离外周血单个核细胞用于抗原特异细胞增殖实验 ;第 5、30、6 0天取肝组织标本进行DHBVDNASouthern杂交、DHB sAg免疫组化及肝组织病理检测。结果 :DHBV感染成年鸭在 1～ 2w潜伏期后出现急性、一过性感染 ,感染高峰期肝内存在多拷贝的DHBV所有复制中间体形式 ,包括cccDNA。进一步分析显示病毒血症的消失是在快速抗原特异细胞增殖反应和高滴度特异抗体产生之后 ;与此同时 ,整个急性感染期间 ,肝细胞并无明显的损害。结论 :非细胞直接损伤机制在嗜肝病毒清除过程中发挥了重要作用。     

人参银杏复方制剂对缺氧复氧后大鼠海马CA1区GABA、Glu表达的影响

目的：探讨人参银杏复方制剂对缺氧复氧后海马CAI区神经元的保护作用机制。方法：应用低压氧舱仿海拔8000米高空缺氧模型，采用免疫组织化学及免疫荧光方法并结合图像分析等技术，观察预防性应用人参银杏复方制剂对缺氧24h复氧0h、24h时段海马CAI区GABA、Glu表达的影响。结果：缺氧24h复氧卟组海马CAI区GABA免疫反应阳性神经元数量、Glu免疫反应阳性神经元荧光强度分别较常氧对照组减少和减弱，复氧24h后上述变化更加明显。预防性应用人参银杏复方制剂后海马CAI区GABA免疫反应阳性神经元数量在复氧0h和24h时较常氧对照组多，以复氧0h时增加最明显；Glu免疫反应阳性神经元荧光强度在复氧0h、24h时段也较缺氧复氧实验组相应时段增加。结论：人参银杏复方制剂可增加缺氧复氧后海马CAI区GABA表达及防止Glu过度释放，对缺氧复氧性脑损伤具有保护作用。