目的评价Klinfelter综合征（KS）患者糖代谢特点，同时探讨KS患者易发生糖代谢紊乱的可能病因。方法回顾性分析1990年以来在解放军总医院就诊的28例KS患者（包括9例合并糖尿病患者）的一般情况、病史资料和实验室检查结果[性腺激素水平...目的评价Klinfelter综合征（KS）患者糖代谢特点，同时探讨KS患者易发生糖代谢紊乱的可能病因。方法回顾性分析1990年以来在解放军总医院就诊的28例KS患者（包括9例合并糖尿病患者）的一般情况、病史资料和实验室检查结果[性腺激素水平、血脂水平、口服75 g口服葡萄糖耐量试验（OGTT）血糖和胰岛素水平]等临床资料。同时选择18例单纯糖尿病患者与9例合并糖尿病的KS患者按照年龄、体质指数（BMI）、病史进行配对。统计学方法采用完全独立样本t检验及配对样本t检验。结果（1）KS人群中糖尿病发生率为32.1%（9/28），染色体核型为47，XXY的患者糖尿病发生率为30.7%（8/26），染色体核型为48，XXYY患者糖尿病发生率为50%（1/2）；（2）合并糖尿病的KS患者与单纯KS患者相比，年龄大、睾酮水平低[分别为（28±8）比（22±4）岁，（2.0±1.3）比（5.4±4.3）nmol/L，t=3.044、-2.249；均P〈0.05]，虽然两组基础胰岛素水平和胰岛素分泌曲线下面积未见显著差异，但合并糖尿病的KS患者胰岛素抵抗指数较单纯KS患者明显增大（6.5±3.4比1.2±2.1，t=3.234，P〈0.05）；（3）KS合并糖尿病患者与单纯糖尿病患者相比，虽然75 g OGTT试验血糖和胰岛素水平一致，但身材更高、体重更重、低密度脂蛋白胆固醇水平更低[分别为（178±12）比（170±6）cm，（91±23）比（80±14）kg，（2.1±0.9）比（2.8±0.5）mmol/L，t=0.750、3.866、-2.681；P〈0.05]；（4）合并糖尿病的KS患者与单纯KS患者及单纯糖尿病患者相比，雌激素/雄激素比值（E/T）高，差异具有统计学意义（t=2.302、2.748；均P〈0.05）。结论（1）KS患者糖尿病发生率明显升高；（2）KS患者易发生糖代谢异常的病因可能包括年龄、睾酮水平低和卵泡刺激素水平高、高E/T值、胰岛素抵抗和X染色体数目异常等。展开更多
Stroke is the second leading cause of death and a major cause of disability worldwide,and biological sex is an important determining factor in stroke incidence and pathology.From childhood through adulthood,men have a...Stroke is the second leading cause of death and a major cause of disability worldwide,and biological sex is an important determining factor in stroke incidence and pathology.From childhood through adulthood,men have a higher incidence of stroke compared with women.Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke.Autophagy is a self-degrading cellular process orchestrated by multiple core proteins,which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes.The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults.Ischemic stroke activates autophagy,however,whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate.Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes.Furthermore,the effects of manipulating autophagy may also differ between the sexes.Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored.In this review,we summarize clinical and pre-clinical evidence for sex differences in stroke.We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy.Finally,we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.展开更多
Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the mo...Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome se-quence for detail characterization and obtain evolutionary status of different genes. The te-locentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majori-ties of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns;about half of the total known genes have only one or two in-trons. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gam-biae. We compared each individual gene of An. gambiae with 33 other taxa having whole ge-nome sequence information. In general, the mosquito Aedes aegypti was found to be ge-netically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in dif-ferent taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were in-ferred which corroborate the previous and pre-sent findings on genetic relationships across various taxa.展开更多
文摘目的评价Klinfelter综合征（KS）患者糖代谢特点，同时探讨KS患者易发生糖代谢紊乱的可能病因。方法回顾性分析1990年以来在解放军总医院就诊的28例KS患者（包括9例合并糖尿病患者）的一般情况、病史资料和实验室检查结果[性腺激素水平、血脂水平、口服75 g口服葡萄糖耐量试验（OGTT）血糖和胰岛素水平]等临床资料。同时选择18例单纯糖尿病患者与9例合并糖尿病的KS患者按照年龄、体质指数（BMI）、病史进行配对。统计学方法采用完全独立样本t检验及配对样本t检验。结果（1）KS人群中糖尿病发生率为32.1%（9/28），染色体核型为47，XXY的患者糖尿病发生率为30.7%（8/26），染色体核型为48，XXYY患者糖尿病发生率为50%（1/2）；（2）合并糖尿病的KS患者与单纯KS患者相比，年龄大、睾酮水平低[分别为（28±8）比（22±4）岁，（2.0±1.3）比（5.4±4.3）nmol/L，t=3.044、-2.249；均P〈0.05]，虽然两组基础胰岛素水平和胰岛素分泌曲线下面积未见显著差异，但合并糖尿病的KS患者胰岛素抵抗指数较单纯KS患者明显增大（6.5±3.4比1.2±2.1，t=3.234，P〈0.05）；（3）KS合并糖尿病患者与单纯糖尿病患者相比，虽然75 g OGTT试验血糖和胰岛素水平一致，但身材更高、体重更重、低密度脂蛋白胆固醇水平更低[分别为（178±12）比（170±6）cm，（91±23）比（80±14）kg，（2.1±0.9）比（2.8±0.5）mmol/L，t=0.750、3.866、-2.681；P〈0.05]；（4）合并糖尿病的KS患者与单纯KS患者及单纯糖尿病患者相比，雌激素/雄激素比值（E/T）高，差异具有统计学意义（t=2.302、2.748；均P〈0.05）。结论（1）KS患者糖尿病发生率明显升高；（2）KS患者易发生糖代谢异常的病因可能包括年龄、睾酮水平低和卵泡刺激素水平高、高E/T值、胰岛素抵抗和X染色体数目异常等。
基金supported by the American Heart Association (856061) to JFMMby the NINDS (R01 5R01NS108779 and 5R01NS094543) to LDM
文摘Stroke is the second leading cause of death and a major cause of disability worldwide,and biological sex is an important determining factor in stroke incidence and pathology.From childhood through adulthood,men have a higher incidence of stroke compared with women.Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke.Autophagy is a self-degrading cellular process orchestrated by multiple core proteins,which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy vesicles fuse with lysosomes or endosomes.The levels and the activity of components of these signaling pathways and of autophagy-related proteins can be altered during ischemic insults.Ischemic stroke activates autophagy,however,whether inhibiting autophagy after stroke is beneficial in the brain is still under a debate.Autophagy is a potential mechanism that may contribute to differences in stroke progression between the sexes.Furthermore,the effects of manipulating autophagy may also differ between the sexes.Mechanisms that regulate autophagy in a sex-dependent manner in ischemic stroke remain unexplored.In this review,we summarize clinical and pre-clinical evidence for sex differences in stroke.We briefly introduce the autophagy process and summarize the effects of gonadal hormones in autophagy in the brain and discuss X-linked genes that could potentially regulate brain autophagy.Finally,we review pre-clinical studies that address the mechanisms that could mediate sex differences in brain autophagy after stroke.
基金Supported by National Natural Science Foundation of China(81071989,81272760)Natural Science Foundation of Guangdong Province(S2011010004178)Science and Technology Program of Guangdong Province(c1221020700008)~~
文摘Understanding the genetic architecture of indi-vidual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolu-tionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome se-quence for detail characterization and obtain evolutionary status of different genes. The te-locentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majori-ties of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns;about half of the total known genes have only one or two in-trons. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gam-biae. We compared each individual gene of An. gambiae with 33 other taxa having whole ge-nome sequence information. In general, the mosquito Aedes aegypti was found to be ge-netically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in dif-ferent taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were in-ferred which corroborate the previous and pre-sent findings on genetic relationships across various taxa.
