Neonatal sunburn and melanoma in mice

Retrospective epidemiological data have indicated that cutaneous malignant melanoma may arise as a consequence of intense, intermittent exposure of the skin to ultraviolet radiation, particularly in children, rather than from the cumulative lifetime exposure that is associated with other forms of skin cancer. Here we use a genetically engineered mouse model to show that a single dose of burning ultraviolet radiation to neonates, but not adults, is necessary and sufficient to induce tumours with high penetrance which are reminiscent of human melanoma. Our results provide experimental support for epidemiological evidence that childhood sunburn poses a significant risk of developing this potentially fatal disease.     

Melanoma biology and new targeted therapy

Melanoma is a cancer that arises from melanocytes, specialized pigmented cells that are found predominantly in the skin. The incidence of melanoma is rising steadily in western populations--the number of cases worldwide has doubled in the past 20 years. In its early stages malignant melanoma can be cured by surgical resection, but once it has progressed to the metastatic stage it is extremely difficult to treat and does not respond to current therapies. Recent discoveries in cell signalling have provided greater understanding of the biology that underlies melanoma, and these advances are being exploited to provide targeted drugs and new therapeutic approaches.     

A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours

Angiogenesis is critical during tumour initiation and malignant progression. Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients. It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies. Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin. Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers.     

Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling

Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue-specific stem cells. Similarly, epithelial tumour maintenance relies on cancer stem cells (CSCs), which co-opt stem cell properties. For most tumours, the cellular origin of these CSCs and regulatory pathways essential for sustaining stemness have not been identified. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Here we identify a population of cells in early epidermal tumours characterized by phenotypic and functional similarities to normal bulge skin stem cells. This population contains CSCs, which are the only cells with tumour initiation properties. Transplants derived from these CSCs preserve the hierarchical organization of the primary tumour. We describe beta-catenin signalling as being essential in sustaining the CSC phenotype. Ablation of the beta-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased beta-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/beta-catenin signalling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate CSCs and consequently eradicate squamous cell carcinomas.     

皮肤生物力学研究进展

综述了皮肤本构理论和建模方法.讨论了普通材料力学方法、离体生物力学方法和活体生物力学方法下获取软组织力学特性参数的测量技术,包括张力计测量、多轴加载测量、钢印挤压测量、气动吸料测量、超声波测量等,列举了皮肤生物力学在生物医学中的皮肤伸展术和扩张术中的应用进展.最后对皮肤生物力学的发展进行了展望.皮肤的本构理论、建模方法、生物力学实验方法也给其他软组织生物力学研究提供了有益的参考和启发.     

利用压汞实验确定岩心麻皮系数 —以鸭儿峡油田白垩系为例

为了分析麻皮效应对鸭儿峡油田白垩系砂砾岩油藏取心分析含油饱和度的影响,综合运用压汞资料、分析化验资料和生产资料,利用岩石物理模型和取心样品对压汞法产生麻皮效应的机理进行系统分析;通过构建J函数,计算油藏的平均毛管压力,并对毛管压力曲线的4个切点开展系统论述;分析油藏排驱压力、不同类型孔喉的进汞饱和度、麻皮效应影响区间和麻皮系数。依据麻皮系数,对岩心含油饱和度进行校正;对校正前后的饱和度参数与阿尔奇公式计算的理论值以及生产资料分别进行对比。结果表明,经麻皮系数校正后的岩心测量含油饱和度较岩心视含油饱和度低15%左右,与测井计算的饱和度和生产资料吻合较好。研究结果一定程度上可为研究区岩心基础资料研究提供技术参考,为油藏饱和度评价及资源量计算提供可靠数据。     

酒渣鼻病皮肤组织病理改变与蠕形螨寄生的关系

观察三种类型酒渣鼻病皮肤组织病理改变，研究人体蠕形螨与其所寄生的皮肤组织病变的关系，为有效治疗酒渣鼻病提供可靠依据。在酒渣鼻病患者面部皮损处扩大的毛囊和增生的皮脂腺中检查出大量蠕形螨成虫、若虫和虫卵，皮肤组织病理改变周围有不同程度的炎症反应。结果表明，蠕形螨寄生与皮肤组织病理改变有密切关系，是酒渣鼻病的重要致病因素之一．提示，治疗酒渣鼻病应采取杀灭螨虫和抑制炎症反应等综合治疗措施疗效较好．     

Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

DNA damage checkpoint genes, such as p53, are frequently mutated in human cancer, but the selective pressure for their inactivation remains elusive. We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis. Progression to carcinoma was associated with p53 or 53BP1 inactivation and decreased apoptosis. A DNA damage response was also observed in dysplastic nevi and in human skin xenografts, in which hyperplasia was induced by overexpression of growth factors. Both lung and experimentally-induced skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites). We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.     

Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity

Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (T(RM)) cells has been proposed. Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8(+) skin T(RM) cells that reside within the entire skin. These skin T(RM) cells are potent effector cells, and are superior to circulating central memory T (T(CM)) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of CD4(+) T cells and interferon-γ, but requires the expression of E- and P-selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that circulating CD8(+) T(CM) and CD8(+) skin T(RM) cells are both generated after skin infection; however, CD8(+) T(CM) cells recirculate between blood and lymph nodes whereas T(RM) cells remain in the skin. Cutaneous CD8(+) T(RM) cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8(+) skin T(RM) cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating T(CM) but no skin T(RM) cells showed greatly impaired viral clearance, indicating that T(RM) cells provide superior protection. Finally, we show that T(RM) cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective T(RM) cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.     

葡萄糖酸氯己定含漱液安全性研究

目的观察葡萄糖酸氯己定含漱液的刺激性和过敏性反应,为临床应用提供参考。方法通过口腔粘膜刺激试验和皮肤过敏试验观察葡萄糖酸氯己定含漱液的刺激性和过敏性。结果葡萄糖酸氯己定含漱液的口腔粘膜刺激试验结果阴性,皮肤过敏试验结果阴性。结论葡萄糖酸氯己定含漱液无刺激性和过敏性。     

氡及其子体对肺以外的组织器官是否有危险

吸入氡子体有致肺癌的危险是辐射防护界公认健康效应之一.文章总结了氡子体致肺癌的流行病调查结果.本文还给出了氡及其子体对其他组织器官所致剂量的计算结果,这些结果可用于评价氡及其子体对身体其他部分的可能危险.跟致肺癌的情况不一样,缺乏其他组织器官假设危害的流行病学调查结果.沉积到皮肤上的氡子体致皮癌的危险和溶于饮水中氡所致胃癌的危险没有过估,但其他危害好象不大.     

Effect of Fabric Elongation on the Making Up of Pressure Garments

Pressure garments are widely used in Hong Kong andmany other countries for burn rehabilitation.Thesegarments are mainly made of elastic Lycra fabrics andtailor-made to individual patient's measurement toprovide an appropriate amount of skin-garment in-terface pressure for medical treatment.However,thefabric tension would be reduced due to fabric elonga-tion under prolonged period of stress,and thus theskin-garment interface pressure cannot be main-tained after repeated use of the garment.This paperaims to study the behaviour of fabric elongation of thefabrics commonly used for making pressure garmentsin U.K.and/or Hong Kong.Attempts to correct theexisting practice of drafting the pressure garments forproviding a more effective clinical treatment.     

地下连续墙垂直承载力试验研究

近年来，把地下连续墙作为承重结构的工程实例越来越多，为了给方后的设计和施工提供合理的依据，我们在国内首次进行了单片的连续墙的垂直静荷载现场试验，对地下墙的荷载传递机理及垂直承载力进行了研究，分析了墙端阻力和侧壁摩阻力随位移发展而发挥的特性及它们之间的相互影响关系，提出了侧壁摩阻力的计算模型及地下连续墙垂直承载力的设计方法，可供工程界参考应用。     

各向异性油藏定向井表皮因子计算方法研究

为了研究定向井近井地带储层渗流规律对表皮因子的影响,采用坐标变换方法将渗透率各向异性介质转换为各向同性介质,建立了适应于各向异性油藏任意井眼轨迹的定向井裸眼完井表皮因子计算模型。在此基础上,应用该模型研究了由于井斜和储层污染产生的表皮因子随井斜角、方位角的变化规律。计算分析表明：在各向异性油藏中,定向井的井眼轨迹对表皮因子具有重要影响。井斜角的减小会导致井斜产生的表皮因子增加,而井斜角、方位角的减小均会导致储层污染产生的表皮因子增加。该模型适用范围广泛,能够为进一步研究定向井的产能提供依据。     

充填防砂井表皮系数研究

从砾石充填防砂井的基本渗流规律出发,将流量的自动分配引入近井各个阻力区,剖析每个阻力区的流速变化,采用压降的形式,推导出了射孔炮眼穿出钻井污染带与未穿出钻井污染带时,污染带与炮眼内流动的层流表皮系数和紊流表皮系数;将常规径向渗流的紊流表皮系数的分析方法引入裂缝渗流紊流表皮系数的分析,导出了压裂充填的紊流表皮系数;同样考虑流速在射孔孔眼附近的急剧增加,推导出了压裂充填的汇聚表皮系数。计算结果与数值解的时比,反映了以上方法的合理性。     

堆载作用下桩体负摩阻力的颗粒流分析

对地面堆载作用下桩土系统的相互作用进行离散颗粒流模拟,分析端承桩在桩周土受柔性分布载荷作用下,桩侧负摩阻力的发展变化趋势,为负摩阻力的研究提供新的方法.数值试验结果表明,负摩阻力的分布随着地表荷载的增加而不断地发生变化,并且当达极限摩阻力后,其值随着桩身位置的不同有不同程度的降低,并非保持不变.     

The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice

When the human immunodeficiency virus transactivating gene under the control of the viral regulatory region is introduced into the germline of mice, skin lesions are induced that resemble Kaposi's sarcoma seen in AIDS. Our findings indicate that HIV could play a direct part in causing cancer.     

皮肤癌表面图象特征提取

本文介绍一种皮肤癌表面图象处理的方法。采用分段线性函数增强皮肤癌表面图象,并利用二维滑动窗分割,实现自动门限提取皮肤癌表面图象特征。     

Temperature monitoring and heating optimization in cancer hyperthermia

A closed form analytical solution to the Pennes' equation with random heating was obtained using the Green s function method. To meet the requirements for the tumor killing temperature and the skin bum threshold, an approach to optimize the cancer hyperthermia parameters was proposed. For clinical practices, a solution to reveal the relationship between skin surface temperature and the transient temperature inside the tissue was obtained. Parametric study shows the feasibility of the heating optimization. The present approach can be incorporated in the apparatus to es¬tablish a noninvasive hyperthermia system.