Molecular mechanisms of gamete recognition and fusion at fertilization

Advances in many areas of reproductive technology have been rapid and, in many respects, have outstripped our knowledge of the fundamental processes of human and animal sperm-egg interactions at fertilization. This is particularly true of human fertilization, where the availability of eggs for research purposes is severely restricted. As a consequence of this, most of the significant advances in our understanding of mammalian fertilization have resulted from studies on animals, particularly the mouse. This review summarizes our current knowledge of the molecular aspects of mammalian fertilization from the point of view of the fertilizing spermatozoon. Particular reference is made to those advances in our knowledge of human fertilization mechanisms. Further understanding of the molecular basis of human fertilization is of paramount importance for the development of new methods of contraception and also for the rational diagnosis and treatment of certain forms of infertility.      

髂-股动脉多层螺旋CT测量

目的:采用16层螺旋CTA对髂-股动脉进行测量,为经髂-股动脉介入诊疗提供影像学数据。方法:收集2010年6月～9月符合要求的连续病例350例,按照年龄21～40岁、41～60岁、61～89岁分为A、B、C组。经肘正中静脉注射对比剂后,用16层螺旋CT进行包括盆腔区的增强扫描,薄层重建图像用容积再现技术对髂-股动脉进行三维重建。测量动脉分叉到髂嵴连线、股骨头上缘连线的垂直距离及动脉分叉夹角。相同性别不同年龄组间采用单因素方差分析,相同年龄组不同性别采用两独立样本t检验,不同侧别间采用配对样本t检验。结果:腹主动脉分叉、左右髂总动脉分叉、左右股总动脉分叉到股骨头上缘连线的垂直距离男性A组分别为(132.5±12.8)mm、(87.1±14.9)mm、(88.8±11.3)mm、(43.4±13.7)mm、(41.5±15.0)mm,B组为(126.5±11.6)mm、(84.8±14.2)mm、(89.1±12.9)mm、(44.3±10.1)mm、(46.2±10.1)mm,C组为(115.6±10.7)mm、(80.3±14.3)mm、(82.3±13.6)mm、(39.1±10.0)mm、(40.4±10.0)mm,女性A组分别为(135.4±12.1)mm、(91.3±15.1)mm、(97.4±14.1)mm、(36.5±10.3)mm、(36.2±10.3)mm,B组为(129.8±12.7)mm、(92.7±12.5)mm、(96.0±13.3)mm、(36.5±10.8)mm、(35.8±10.9)mm,C组为(121.2±13.1)mm、(84.0±11.3)mm、(86.3±11.4)mm、(36.4±12.2)mm、(36.9±11.0)mm。除男性左髂总动脉分叉、女性左右股总动脉分叉到股骨头上缘连线的垂直距离外,不同年龄组间差异均有统计学意义(P<0.05)。腹主动脉分叉夹角、左右髂总动脉分叉夹角男性A组分别为(38.2±5.8)°、(26.6±16.9)°、(30.5±10.8)°,B组为(38.1±11.3)°、(25.3±10.8)°、(24.8±11.2)°,C组为(45.1±16.5)°、(25.8±12.5)°、(25.6±13.2)°,女性A组分别为(46.9±10.9)°、(28.2±13.5)°、(28.9±10.2)°,B组为(40.7±11.2)°、(20.3±10.3)°、(21.6±9.7)°,C组为(45.1±11.2)°、(21.0±9.9)°、(27.0±12.1)°,男女腹主动脉分叉夹角、男性左右髂总动脉分叉夹角不同年龄组间差异有统计学意义(P<0.05)。两侧对比三组的髂总动脉分叉点至股骨头上缘连线垂直距离差异均有统计学意义(P<0.05)。结论:16层螺旋CTA可对髂-股动脉进行准确测量,为介入诊疗提供数据。     

Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

AimWeight change during adult life may reflect metabolic changes and influence colorectal cancer (CRC) development, but such role is not well established. We aimed to explore the association between adult weight change (from age 20 to 50) and CRC risk. In particular, we investigated differences according to colon and rectal cancer, sex and measures of attained adiposity.MethodsWe included 201,696 participants from six participating countries in the European Prospective Investigation into Cancer and Nutrition (1992–2010). During a mean follow-up of 11.2 years 2384 (1194 in men and 1190 in women) incident CRC cases occurred. Cox proportional hazard models adjusted for body mass index at age 20 and lifestyle factors at study recruitment were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAfter multivariable adjustment, each kg of weight gained annually from age 20 to 50 was associated with a 60% higher risk of colon cancer (95% CI 1.20–2.09), but not rectal cancer (HR 1.13, 95% CI 0.79–1.62, P_interaction = 0.04). The higher risk of colon cancer was restricted to people with high attained waist circumference at age 50 (HR 1.82, 95% CI 1.14–2.91, P_interaction = 0.02). Results were not different in men and women (P_interaction = 0.81).Conclusion(s)Adult weight gain, as reflected by attained abdominal obesity at age 50, increases colon cancer risk in both men and women. These data underline the importance of weight management and metabolic health maintenance in early adult life years for colon cancer prevention.     

格列美脲与格列本脲治疗2型糖尿病疗效的系统评价

目的系统评价格列美脲与格列本脲治疗T2DM的疗效。方法计算机检索PubMed、万方等数据库从建库至2010年12月间的有关文献。按Cochrane系统评价的方法评价纳入研究的质量,使用Review Manager4．2软件进行荟萃分析。结果共纳入9个随机对照试验。结果显示：格列美脲在降低HbA1c[P=0．08,加权均数差（WMD）=-0．18,95％CI（-0．39,0．02）]、FPG[P=0．06,WM=-0．46,95％CI（-0．94,0．01）]、餐后血糖[P=O．73,WMD=-0．16,95％CI（-1．08,0．76）]、TC[P=0．22,WMD=-0．2,95％CI（-0．51,0．12）]和TG[P=0．06,WMD=-0．30,95％CI（-0．61,0．01）]方面与格列本脲无差异;在相同血糖水平下,格列美脲组FIns[P〈0．05,WMD=-0．83,95％CI（-1．21,0．45）]及餐后胰岛素[P〈0．05,WMD=-5．94,95％CI（-8．79,-3．10）]升高程度低于格列本脲组;低血糖发生率格列美脲组低于格列本脲组[P〈0．05,RR=0．66,95％CI（0．53,0．81）];在降低BMI方面格列美脲优于格列本脲[P=0．02,WMD=-1．49,95％CI（-2．7,-0．27）]。结论与格列本脲相比,格列美脲在降低血糖的同时,还能改善胰岛素抵抗及减轻体重,且低血糖发生率低,是安全有效的治疗T2DM的药物。     

吲哚美辛对β淀粉样蛋白1-42诱发BV-2细胞产生炎性介质的抑制作用

目的研究吲哚美辛对β淀粉样蛋白1-42（Aβ1-42）刺激小胶质细胞释放炎性介质一氧化氮（NO）及白细胞介素-1β（IL-1β）的抑制作用。方法应用高度纯化的BV-2小胶质细胞作为体外小胶质细胞模型，应用不同浓度吲哚美辛（10^-9，10^-8，10^-7，10^-6，10^-5mol／L）与20μmol／LAβ1—42单独或同时培养12h，测定细胞上清NO及IL，1β含量；RT—PCR法测定BV-2细胞iNOSmRNA及IL-1βmRNA的表达。结果吲哚美辛单独作用对BV-2细胞产生NO、IL-1β及iNOSmRNA、IL-1βmRNA表达无明显作用。Aβl—42可以刺激BV-2细胞产生NO及IL-1β，并增加iNOSmRNA及IL-1βmRNA表达，这种作用均可被吲哚美辛所抑制，在吲哚美辛浓度为10^-7～10^-5mol／L时抑制作用较为明显。结论在体外吲哚美辛可以降低Aβ1—42介导的BV-2细胞iNOSmRNA及IL-1βmRNA表达，从而减少NO及IL-1β的产生，上述抑制作用可能参与了吲哚美辛在阿尔茨海默病治疗中的神经元保护机制。     

The efficacy of CD3 x CD19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2

To evaluate the potency by which human T cells are targeted and activated by bispecific monoclonal antibodies (BsAbs) to lyse tumor cells, a clonogenic assay was developed. The efficacy of a CD3 x CD19 BsAb binding to both the CD3 T-cell antigen and the CD19 B-cell antigen was already proven in 51Cr-release assays and in 3-day activation cultures. To achieve more quantitative results, a 14-day clonogenic assay, based on limiting-dilution, was performed for the determination of the initial and residual number of clonogenic units obtained with a CD19+ pre-pre-B acute lymphoblastic leukemia (ALL-B) cell line. Elimination of up to 5 logs of ALL-B cells by freshly isolated peripheral blood mononuclear cells (PBMCs) cultured with BsAb plus interleukin-2 (IL-2) could be detected. The presence of human IgG did not abolish the effect. Repeated addition of each of the two agents was necessary, because a single treatment produced only a 1- to 2-log kill. CD3 monoclonal antibody and IL-2 stimulation ("lymphokine-activated killer cell" conditions) resulted in only a 2-log kill. The number of T cells proved critical in lysis of ALL-B cells, with a 5-log kill using a T-cell:B-cell ratio of 3:1 but with only a 1-log kill using a ratio of 1:1. PBMCs isolated from patients with non-Hodgkin's lymphoma, both in relapse or remission, proved to be as competent as those from healthy donors in removing ALL-B cells. This clonogenic assay shows the importance of repeated administration of CD3 x CD19 BsAb and IL-2 and offers the possibility to compare it with other therapies in B-cell malignancy.     

TCA: a polymorphic genetic marker in leukemias and melanoma cell lines

TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T- ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.     

Hip joint range of motion reduction in sports-related chronic groin injury diagnosed as pubic bone stress injury

Traumatic osteitis pubis is a non-specific entity that relates to chronic groin injury and has recently been described as being akin to a pubic bone stress injury. It is uncertain whether or not reduction of hip joint range of motion occurs in traumatic osteitis pubis. The purpose of this study was to establish whether there is a reduction of hip range of motion in athletes who have chronic groin injury diagnosed as pubic bone stress injury. A case-control study was performed whereby 89 Australian Rules footballers underwent, with clinical history unknown, clinical and MRI examination of the groin region. Clinical criteria (pain with tenderness) and MR-criteria (pubic bone marrow oedema) were used for diagnosis of pubic bone stress injury. End-range internal and external rotation hip motion was measured using a goniometer. Athletes with and without symptoms were compared, as were athletes with current symptoms with athletes who had recovered from their groin pain episode. Chronic groin injury was diagnosed in 47 athletes with 37 having pubic bone stress injury. Thirteen athletes had previous groin injury. A reduction of internal and external hip range of motion was demonstrated in athletes with pubic bone stress injury (p < 0.05) and in athletes who had current symptoms compared to those who had recovered from their groin pain episode (p < 0.05). A reduction in hip range of motion was evident in athletes with chronic groin injury diagnosed as pubic bone stress injury. There may be a role for increasing hip range of motion in rehabilitation.