摘要：A novel reconstructive prosthesis was designed with topological optimization(TO)and a lattice structure to enhance biomechanical and biological properties in the proximal *** biomechanical performance was validated through finite element analysis(FEA)and biomechanical *** tibia with inhomogeneous material properties was reconstructed according to computed tomography images,and different components were designed to simulate the *** compliance TO subject to a volume fraction constraint combined with a graded lattice structure was utilized to redesign the *** was performed to evaluate the mechanical performances of the tibia and implants after optimization,including stress,micromotion,and strain *** results were analyzed by paired-samples t tests,and p<0.05 was considered *** testing was used to verify the tibial *** to the original group(OG),the TO group(TOG)exhibited lower stress on the stem,and the maximum von Mises stresses were 87.2 and 53.1 MPa,respectively,a 39.1%reduction(p<0.05).Conversely,the stress and strain energy on the tibia increased in the *** maximum von Mises stress values were 16.4 MPa in the OG and 22.9 MPa in the TOG with a 39.6%increase(p<0.05),and the maximum SED value was 0.026 MPa in the OG and 0.042 MPa in the TOG,corresponding to an increase of 61.5%(p<0.05).The maximum micromotions in the distal end of the stem were 135μm in the OG and 68μm in the TOG,almost a 50%*** stress curves of the biomechanical test coincided well with the FEA *** TO approach can effectively reduce the whole weight of the prosthesis and improve the biomechanical environment of the *** could also pave the way for next-generation applications in orthopedics surgery.

摘要：The introduction of designer oestrogens as a treatment modality in hormone replacement in women has invited toconsider the concept of compounds with selective androgenic effects for male hormone replacement therapy. The fullspectrum of the actions of testosterone may not be necessary of even undesired for certain indications for testosteronetreatment. To define for what indications certain androgenic properties are desired and undesired more insight in basicandrogen (patho)physiology is required. There is convincing evidence that aromatization of androgenic compounds tooestrogens might be an advantage for maintenance of bone mass and it might also mitigate negative effects of androgenson biochemical parameters of cardiovascular risks; the potentially negative effects of oestrogens on prostate pathology inageing men needs further elucidation. While the role of dihydro-testosterone (DHT) for the male sexual differentiationand for pubertal sexual maturation is evident, its role in mature and ageing males seems less significant or may even beharmful. It is, however, of note that a negative effect of DHT on prostate pathophysiology is certainly not *** male contraception a progestational agent with strong androgenic properties might be an asset. For most of theandrogenic actions the critical levels of androgens are not well established. The latter is relevant since the large amountof androgen molecules required for its biological actions (as compared to oestrogens)is an impediment in androgenreplacement modalities. There may be room for more biopotent androgens since delivery of large amounts of androgenmolecules to the circulation poses problems for treatment modalities.

摘要：AIM:To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal ***:The acellular cornea matrix (ACM) were prepared from de-epithelium fresh porcine corneas (DFPCs) by incubation with 100% fresh human sera and additional electrophoresis at 4℃. Human corneal epithelial cells (HCEs) were used for the cytotoxicity tests of ACM. ACM were implanted into the Enhanced Green Fluorecence Protein (eGFP) transgenic mouse anterior chamber for evaluation of ***:HE and GSIB4 results showed fresh porcine cornea matrix with 100% human sera and electrophoresis could entirely decellularize stromal cell without reducing its transparency. ACM has no cytotoxic effect ex vivo. Animal test showed there was no rejection for one month after ***:These results provide a decellularizing approach for the study of corneal tissue engineering and had the broader implications for the field of biological tissue engineering in other engineered organ or tissue matrix.

摘要：21世纪的医学已经发生了翻天覆地的变化，许多新的技术和手段可以更早地发现和治疗疾病。但是，随着技术的不断进步，医学却并没有满足人们日益增高的医疗需求。本文从临床医师的角度出发，阐明艺术在医学思考和活动中的重要性，通过增加医学的艺术性而改善目前的医疗现状和医患关系。

摘要：Focal adhesion kinase(FAK)is an intracellular tyrosine kinase that plays a critical role in the occurrence,development,and metastasis of cancer through both its kinase-dependent catalytic functions and kinase-independent scaffolding *** kinase inhibitors target only its catalytic activity,leaving the scaffolding functions ***,proteolysis targeting chimeras(PROTACs)offers a promising approach by degrading the entire FAK protein,thereby inhibiting both functions *** this study,we designed and synthesized novel PROTAC degraders,utilizing a defactinib derivative(compound 12)as the FAK ligand and a lenalidomide analog as the E3 ligase *** structures of these compounds were confirmed through^(1)H NMR,^(13)C NMR,and high-resolution mass spectrometry(HRMS).Among the synthesized compounds,the optimized compound 16b exhibited potent degradation activity against FAK protein in A549 cells,with a DC_(50)of 6.16±1.13 n M,significantly inhibiting the proliferation and colony formation of these *** to defactinib,16b showed enhanced inhibition of A549 cell migration and ***,our research demonstrated that the rapid and effective FAK degradation induced by 16b was mediated by a CRBN-dependent proteasome mechanism.

摘要：Objectives: To study the potential of embryo transfer after 3, 4 or 5 days of embryo culture under the German embryo protection law according to which only a maximum of three zygotes are allowed to be cultured for embryo transfer. Study design: In a prospective study, 273 patients with assisted reproductive treatment were randomly allocated for transfer on days 3, 4 or 5. Pregnancy and implantation rates were evaluated in regard to day of transfer and results were compared by Chi-square or ANOVA test. Results: Out of 234 transfer cycles, 79 were performed on day 3, 76 on day 4 and 79 on day 5. Pregnancy and implantation rates were 41.8%/27.1%for transfer on day 3, 27.6%/14.1%for day 4 transfer and 16.5%/8.8%for transfer on day 5. These results were significantly different for pregnancy rates on day 3 versus day 5 (P < 0.001) and for implantation rates on day 3 versus day 4 (P < 0.005) and day 3 versus day 5 (P < 0.001). Conclusions: These findings suggest that extended embryo culture is not beneficial when the option for embryo selection at later stages of development is not available.

摘要：目标 研究原发性甲状旁腺功能亢进症手术前后肾结石发生的危险及危险因素。 设计 以登记为根据,设立对照的回顾性随访研究。 背景 丹麦的三级医院。 入选者674例手术证实为甲状旁腺功能亢进的连续病人。与每例病人年龄及性别相匹配的3名来自普通人群者做为随机对照。比较病人及对照者因肾结石而住院的情况。评估病人发生肾结石的危险因素。 主要结果测定 肾结石发生次数;病人及对照者因肾结石而住院的比较;评估病人肾结石的危险因素。 结果 结石发生的相对危险性术前为40(95％可信区间为31～53),而术后为16(12～23)。术前10年的危险性增加,而术后10年以后变为正常。病人术后20年无结石生存率为90.4％,而对照为98.7％(危险差8.3％,48％～11.7％)。术前有结石的病人术后发生结石的危险性是对照的27倍。术前,男性结石发病高于女性且年轻者多于年长者。甲状旁腺的病理形态、切除组织量、血浆钙水平以及骨骼病变(骨折)都不影响发生肾结石的危险性。术后,年轻、术前有结石及尿道狭窄是发生结石有意义的危险因素。 结论 原发性甲状旁腺功能亢进症肾结石的危险增加而术后降低。手术10年以后危险恢复正常。术前有结石的病人术后发生结石的危险增加。有结石及无结石者中发生骨骼并发症的危险相同。

摘要：目的探讨在绝经早期妇女中使用激素补充治疗（HRT）对心血管结局的长期影响。研究设计开放标签，随机对照研究研究地点与开始时间丹麦，1990--1993。试验对象1006名健康妇女，年龄45～58岁，绝经早期或有围绝经期症状并且记录绝经后血清卯泡刺激素（FSH）值。经随机分配，其中502例为接受激素补充治疗组，504例为不接受治疗的对照组。曾行子宫切除术的年龄45～52岁且记录绝经期后血清FSH值的妇女也纳入研究。

摘要：背景：颈动脉内膜中层厚度（carotid artery intima—media thickness，CIMT）是冠状动脉粥样硬化的一种标志物，可以独立地预测心血管事件的发生。2型糖尿病患者心血管事件有所增加。尽管相对短期的研究显示，噻唑烷二酮类药物（例如匹格列酮）可以减缓CIMT的进展，但是长期研究结果目前尚不明确。目的：与格列美脲比较，评估匹格列酮对2型糖尿病患者颈总动脉CIMT变化的影响。设计、地点及参试者：2003年10月至2006年5月于芝加哥城区28家临床单位收治的2型糖尿病患者中进行随机、双盲、对照、多中心试验。治疗期为72周（随访1周）。在每个中心由一位超声检查操作者采集CIMT影像，由一位不了解治疗分组情况的判读者应用自动边缘检测技术进行判读。462例2型糖尿病成人患者（平均年龄，60[SD，8．1]岁；平均体重指数，32[SD，5．1]；平均病程7．7[SD，7．2]年；平均糖化血红蛋白值[HbA1c]，7．4％[SD，1．0％]）或者为新近确诊，或者为目前已接受饮食／锻炼、磺酰脲类、二甲双胍、胰岛素或联合治疗的患者。干预：盐酸匹格列酮（15—45 mg／d）和作为有效比较的格列美脲（1—4mg／d）。主要观测指标：与基线比较，最后随访时左右两侧颈总动脉后壁平均CIMT的绝对变化。结果：与格列美脲比较，各时点（24、48、72周）匹格列酮组CIMT的平均变化较小。72周时，匹格列酮组与格列美脲组比较，平均CIMT进展一级终点较小（分别为-0.001mm和＋0．012mm；差别为-0．013mm；95％可信区间，-0．024至-0．002；P=0．02）。与格列美脲比较，匹格列酮还可减缓最大CIMT进展（72周时分别为0．002mm和0．026mm；差别为-0．024mm；95％可信区间，-0．042至-0．006；P=0．008）。在根据年龄、性别、收缩压、DM病程、体重指数、Hb1C。值以及他汀类药物使用预先确定的各亚组间，匹格列酮对平均CIMT的有益效应相似。结论：与格列美脲比较，在为期18个月的治疗期间，匹格列酮减缓了2型糖尿病患者CIMT的进展。

摘要：背景：为增强饮食治疗降低胆固醇的效果，国家胆固醇教育计划(National Cholesterol Education Program，NCEP)成人治疗小组(Adult Treatment Panel，ATP)III强调食用低饱和脂肪以及植物固醇和粘胶纤维食物，而美国心脏病协会(American Heart Association，AHA)则支持食用大豆蛋白和坚果。目的：确定食用含有这些推荐食物所有成分的食物是否可以取得类似于3-羟-3-甲戊二酰辅酶A还原酶抑制剂(他汀类)的降低胆固醇的效果。设计：于2002年10月至12月间进行的随机对照试验。地点和参试者：从一家加拿大医院的营养研究中心和社区入选46例成年高脂血症患者(25例男性和21例已绝经女性)，平均年龄(SE)59岁(1岁)，体重指数27．6（0．5)。干预：参与者随机分配至以下三种干预门诊治疗1个月：极低饱和脂肪饮食，以碾碎的全麦谷类食品和低脂奶制品为基础(n=16；对照组)；极低饱和脂肪饮食加洛伐他汀20mg/d(n=14，他汀组)；富含植物固醇(1．0g／1000kcal)、大豆蛋白(21．4g／1000kcal)、粘胶纤维(9．8g／1000kcal)和杏仁(14g／1000kcal)的饮食(联合饮食组)。主要观察指标：血脂和C-反应蛋白水平，来自空腹血样；血压；体重；在0周、2周和4周时分别测量这些指标，并在三组间比较。结果：对照组、他汀组和联合饮食组低密度脂蛋白胆固醇分别平均(SE)下降8．0％(2．1％)(P=0．002)、30．9％(3．6％)(P<0．001)和28．6％(8．6％)(P<0．001)。C-反应蛋白分别下降10．0％(8．6％)(P=0．27)、33．3％(8．3％)(P=0．002)和28．2％(10．8％)(P=0．02)。他汀组和联合饮食组降低程度明显大于对照组。他汀治疗和联合饮食治疗的效果无显著差异。结论：研究显示，在同一饮食方案中，降胆固醇成分的多样化增加了饮食治疗高胆固醇血症的效果。