BRAF、NRAS癌基因与恶性黑素瘤的研究

近年来,世界范围内黑素瘤的发生率正逐渐升高,发病年龄也愈来愈早,其死亡率也随之增加.环境因素和遗传易感因素是恶性黑素瘤发病的主要机制.遗传易感性的研究发现,与散发性恶性黑素瘤发病密切相关的两个遗传易感基因是位于RAS-RAF-MEK-ERK途径的BRAF、NRAS基因.其中BRAF基因是黑素瘤中突变率最高的基因,也是目前黑素瘤特异性靶向治疗研究的热点基因.概述BRAF、NRAS基因突变在恶性黑素瘤形成、发生、发展中所起的重要作用,并评述BRAF基因突变在黑素瘤临床诊治上的应用价值.     

Proteoglycans and cutaneous vascular defense and repair

Proteoglycans are hybrid molecules composed of a core protein and covalently attached glycosaminoglycan chain(s). The structure, location, and processing of these molecules enables them to encode specific information that is used in multiple physiologic processes. Endothelial cells in the skin are influenced by proteoglycans through binding interactions between glycosaminoglycans and extracellular matrix, growth factors, cytokines, adhesion receptors, enzymes, and enzyme inhibitors. In wound repair, proteoglycans such as the syndecans are induced by antimicrobial peptides and can control growth factor responsiveness. The glycosaminoglycans further signal endothelial cells to increase expression of ICAM-1 and other molecules important for leukocyte adhesion. Thus, proteoglycans represent a powerful central regulatory element in skin that influences a wide variety of events and participates in host defense and tissue repair.     

Aspirin and NSAID use and keratinocyte cancers

It is thought that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) may protect against keratinocyte skin cancers, i.e. squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). However, the evidence for this is scant. The authors, based in Queensland, Australia, studied a group of middle-aged or elderly Queensland residents obtained from the register of voters (the QSkin study). They compared the incidence of keratinocyte cancers in a three-year period in individuals who self-reported taking aspirin or another NSAID regularly, with those who did not. In patients at high risk (such as having a history of previous skin cancer or multiple patches on the skin called actinic lesions) they found that taking aspirin infrequently (less than once a week) was associated with a slightly reduced risk of SCC. Regular use of other NSAIDS (at least once a week) led to a slightly reduced risk of BCCs. In low-risk patients (no history of skin cancer and fewer than 5 actinic lesions) the authors found no reduced risk from taking aspirin or other NSAIDs. The authors comment that many patients are on low dose aspirin to reduce the risk of heart attacks or strokes, but this may be inadequate to prevent skin cancer. As most patients purchase non-steroidal drugs over the counter, it was not possible to determine dosage and duration of treatment. They conclude that the protective effect of NSAIDS is slight and only of value in patients at high risk.     

Itch and scratch: scabies and pediculosis

Scabies and lice infestations are almost an everyday diagnosis in the dermatology clinics. Along with the unbearable itch, resistance to medication, secondary infection, and the high risk for spreading the parasite to their close contacts, the patients have also to battle with many myths, prejudice, and shames connected to those infestations.     

Lumps and bumps in neonates and infants

There are many developmental abnormalities that may appear in the neonate and in infants when critical steps in embryogenesis fail. These steps are often not fatal but can lead to significant morbidity for those patients affected. A logical approach is needed in addressing both the diagnostic and therapeutic issues that arise when caring for these patients, as various lesions will warrant an observational approach, and others may require imaging studies or definitive surgical intervention. Additionally, there are other "lumps and bumps" that are seen in the neonatal and infantile age groups that include malignancies and cutaneous neoplasms with associated systemic sequelae.     

Understanding and Evaluating Systematic Reviews and Meta-analyses

A systematic review is a summary of existing evidence that answers a specific clinical question, contains a thorough, unbiased search of the relevant literature, explicit criteria for assessing studies and structured presentation of the results. A systematic review that incorporates quantitative pooling of similar studies to produce an overall summary of treatment effects is a meta-analysis. A systematic review should have clear, focused clinical objectives containing four elements expressed through the acronym PICO (Patient, group of patients, or problem, an Intervention, a Comparison intervention and specific Outcomes). Explicit and thorough search of the literature is a pre-requisite of any good systematic review. Reviews should have pre-defined explicit criteria for what studies would be included and the analysis should include only those studies that fit the inclusion criteria. The quality (risk of bias) of the primary studies should be critically appraised. Particularly the role of publication and language bias should be acknowledged and addressed by the review, whenever possible. Structured reporting of the results with quantitative pooling of the data must be attempted, whenever appropriate. The review should include interpretation of the data, including implications for clinical practice and further research. Overall, the current quality of reporting of systematic reviews remains highly variable.     

Epidemiology and control and curable sexually transmitted diseases: opportunities and problems

BACKGROUND: Despite the availability of safe and effective treatment, infection with bacterial sexually transmitted diseases persists at a high prevalence in many populations. GOAL: To review the difficulties of parameter estimation when a cure is readily available and to explore the impact of different treatment and screening strategies that might maximize the benefits of using available treatments. STUDY DESIGN: A standard deterministic model for the spread of a bacterial sexually transmitted disease that causes symptomatic and asymptomatic infections, in which the population is stratified according to sex and sexual activity, is further stratified into two host groups to enable the modeling of different treatment and screening strategies. RESULTS: In the presence of a core group, if an infection has a high transmission probability, then screening for asymptomatic infections has a short-lived benefit. Repeated screening is slightly better if it is not restricted to a fraction of the at-risk population, but targeting of high-risk groups should be effective. Screening to treat asymptomatic infections in men could be beneficial if a substantial fraction of cases remain asymptomatic. CONCLUSIONS: After the initial gains achieved through treating symptomatic infections, further reductions in the prevalence of infections can be achieved by finding asymptomatic infections. However, these gains are difficult to achieve, especially in the case of gonorrhea. Because men are likely to have an asymptomatic chlamydial infection, screening of men for chlamydia should be worthwhile.     

皮肤激光与光子:进展与现状

1治疗理论1.1选择性光热作用原理选择性光热作用原理(theory of selective photothermolysis)是1983年Anderson等提出来的,其精