BACKGROUND & AIMS: :Orphan medicinal products (OMPs) are targeted at the diagnosis, prevention or treatment of rare diseases and have a special status in European law. This status brings incentives for pharmaceutical companies to invest in OMP development. The goal of the legislation is to encourage the development of more treatments for life-threatening rare disorders, but increased availability of OMPs raises important issues surrounding the public funding of very expensive treatments by national health services. In this article we review OMPs and the incentives for their development and discuss the challenges presented by funding these treatments.

背景与目标： : 孤儿药品 (OMPs) 针对罕见疾病的诊断，预防或治疗，在欧洲法律中具有特殊地位。这种状态为制药公司投资OMP开发带来了动力。该立法的目标是鼓励为危及生命的罕见疾病开发更多的治疗方法，但是omp的可用性增加引发了围绕国家卫生服务机构为非常昂贵的治疗提供公共资金的重要问题。在本文中，我们回顾了omp及其发展的诱因，并讨论了资助这些治疗带来的挑战。

BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

背景与目标： 抗原特异性T细胞参与胶原疾病的发病机理仍存在争议。胶原蛋白疾病的最后阶段通常以炎症为主。因此，抗原非特异性因子 (如炎性细胞因子) 可能在这一过程中起重要作用。另一方面，用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里，我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法，回顾了我们的新型T细胞克隆分析系统。使用该方法，可以在体内和体外评估抗原刺激过程中T细胞克隆积累的动态变化。使用类风湿关节炎和系统性红斑狼疮患者获得的数据讨论了抗原特异性T细胞克隆在胶原疾病中的意义。

BACKGROUND & AIMS: :The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.

背景与目标： : 这项研究的目的是找出3分之1一家香水工厂的工作人员的皮肤病的原因，该工厂生产了10种不同的香水喷雾剂。现场检查，皮肤科检查和所有26名有风险的人使用4种香料油和30种成分进行贴剂测试。结果显示，6名装瓶工人患有过敏性接触性皮炎，2名来自刺激性接触性皮炎，12名工人对各种香料表现出不同的强烈反应。过敏性接触性皮炎的主要病因为香精油2种 (12例)，其成分为香叶醇 (12例)，苯甲醛 (9例)，肉桂醛 (6例)，芳樟醇，橙花油，柠檬油和橙油的萜烯 (4例)。没有人对秘鲁的香脂测试呈阳性。办公室工作人员，包装工或打印机的工作变更到其他房间，他们不再与香水接触，导致了定居。总而言之，用非易碎材料和使用手套的墨盒自动化和更换玻璃瓶可以最大程度地降低风险。

BACKGROUND & AIMS: :Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.

背景与目标： : 通过三种不同的方法研究了72例肿瘤患者和10例非肿瘤性结肠疾病的雌激素受体 (ER) 的存在。只有7个标本 (6个原发性腺癌和1个复发性癌症) 的ER浓度高于3 fm/mg的胞质蛋白，没有性别，年龄和肿瘤分期的相关性。我们的结果表明，大肠不含雌二醇的胞质受体。

BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To describe the prevalence of oral diseases and their impact on oral-health-related quality of life in people with severe mental illness undertaking community-based psychiatric care. METHODS:A survey was conducted at eight outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and twelve consecutive patients with mental illness were invited to participate in this study. They were clinically examined and asked to complete the oral health impact profile (OHIP) questionnaire. RESULTS:The response rate was 79% (n = 89); 57 (64%) males and 58 persons over 45 years of age (65%) participated in this survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%) respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and 14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%) of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:Overall, this survey found that oral health has a great impact on patients with severe mental illness being treated in the community setting and their oral health is poorer than the national adult general population. Future research should consider the causes that relate to the poorer oral health in this population and potential health promotion mechanisms in this population to encourage an upstream approach to health.

背景与目标：

BACKGROUND & AIMS: :From 1982 to 1987, 2,433 lesions of the thyroid gland in 1,796 patients were examined by fine needle aspiration (FNA). Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected (unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43%, a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from nonmalignant follicular neoplasms, and papillary thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as "suspect lesion."

背景与目标： : 从1982个1987年中，通过细针穿刺 (FNA) 检查了1,796例患者的2,433个甲状腺病变。细胞病理学将66.91% 抽吸物分类为良性，10.76% 为甲状腺炎，4.89% 为疑似 (未指定) 肿瘤，1.31% 为恶性肿瘤阳性，16.11% (392) 为不满意。将257例的组织学诊断与细胞学诊断进行比较，以确定甲状腺病变的FNA细胞学检查的准确性，从而产生71.43% 的敏感性，100% 的特异性和95.09% 的准确性。该数据强烈支持甲状腺FNA作为重要的术前诊断工具。滤泡癌在细胞学上很难与非恶性滤泡肿瘤区分开来，而老年患者直径小于2厘米的甲状腺乳头状癌经常被误诊或仅被诊断为 “可疑病变”。

BACKGROUND & AIMS: :Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.

背景与目标： : senataxin (SETX) 基因的突变可导致肌萎缩性侧索硬化症4 (ALS4)，这是一种常染色体显性遗传形式的少年性肌萎缩性侧索硬化症，或导致常染色体隐性遗传性共济失调并伴有动眼失用2型。对于可能的疾病原因，尤其是错义变异，必须谨慎行事。在这里，我们评估了所有先前报道的SETX错义突变以及54例怀疑患有als4的患者中新发现的六个变异的重要性。然而，流行病学和计算机证据表明，所有新发现的变异和两个先前发表的ALS4-related错义变异 (C1554G和I2547T) 最有可能是非致病性的，证明了在缺乏功能测定的情况下解释SETX错义等位基因的问题。

BACKGROUND & AIMS: :The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

背景与目标： : p38丝裂原活化蛋白激酶 (MAPK) 抑制剂的抗炎潜力被巧合地扩展为对p38α MAPK和磷酸二酯酶4 (PDE4) 的双重抑制，并且两种炎症相关酶的阻断所产生的潜在益处被彻底研究。在对啮齿动物，狗和猴子施用1之后，在体外实验以及体外和体内临床前研究中相继评估了最有希望的化合物CBS-3595 (1)。所得数据清楚地表明有效抑制了肿瘤坏死因子 α 的释放。为了在向健康的人类志愿者施用1时再次确认动物研究的结果，进行了I期临床试验。除了有关1的药代动力学和药效学特征的进一步信息外，还证明了p38α MAPK和PDE4的双重抑制能够协同减弱过度的抗炎反应。

BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.

背景与目标：

BACKGROUND & AIMS: :The prevalence of renal diseases is rising and reaching 5-15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of "personalized medicine" with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

背景与目标： : 肾脏疾病的患病率正在上升，并达到成年人口的5-15%。肾脏损害与机体稳态紊乱以及外源性和内源性元素 (包括药物和代谢物) 之间平衡的丧失有关。研究表明，肾脏疾病不仅受环境影响，还受遗传因素影响。在某些情况下，该疾病是由单个基因突变引起的，当时的严重程度取决于一个或两个突变等位基因的存在。在其他情况下，肾脏疾病与一个或多个基因内的改变有关，但环境因素也是疾病发展所必需的。因此，似乎遗传方面的分析应该是临床和实验研究的自然组成部分。个性化医疗的目标是在正确的时间为正确的患者确定正确的药物。全基因组检查可能有助于改变疾病和患者的治疗方法，从而创建具有基于每个个体遗传背景设计的新诊断和治疗策略的 “个性化医学”。在药物基因组学分析中识别高危患者将有助于避免许多不必要的副作用，同时优化单个患者的治疗效果。肾脏疾病的个性化治疗仍处于初步阶段，这主要是由于此类分析的高昂成本和人类基因组的复杂性。这篇综述将集中在几个感兴趣的领域: 肾脏疾病的发病机制，诊断，治疗，进展率和预后预测。

BACKGROUND & AIMS: OBJECTIVE:Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease.

METHODS:Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed.

RESULTS:There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03).

CONCLUSIONS:IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

背景与目标： 目的 : 炎症性肠病的遗传易感性已广为人知。也有越来越多的证据表明粘膜免疫系统的激活和炎性细胞因子的产生，即炎症性肠病中的白介素 (IL)-1ra和IL-1beta。本研究的目的是分析克罗恩病 (CD) 或溃疡性结肠炎 (UC) 患者中这些基因的不同等位基因之间的IL-1beta和IL-1ra基因多态性以及连锁不平衡系数。根据疾病的严重程度。
方法 : 本研究纳入了28例炎症性肠病患者 (87 UC和141 CD)，并与113例无关的对照进行了比较。通过PCR对可变区进行特异性扩增后，研究了IL-1beta和IL-1ra基因多态性。分析了五等位基因多态性，对应于位于IL-1ra基因内含子2中的VNTR区域，而分析了IL-1beta基因511位的两种限制酶 (TaqI和AvaI) 显示的双等位基因rflp。
结果 : 基因型分布在对照组和CD或UC患者之间没有显着差异。然而，与非手术UC患者相比，手术治疗的UC患者的特征是基因型IL-1ra 1-2的频率更高 (39 vs 16%，pc <0.01)。此外，与手术治疗的UC患者 (14 vs 34%，pc <0.002) 或对照 (14 vs 30%，pc <0.005) 相比，非手术UC患者显示出较低的IL-1ra等位基因2频率。此外，对位于2号染色体相同区域的IL-1beta和IL-1ra基因的同时分析表明，携带IL-1beta等位基因2的CD患者更经常是IL-1ra等位基因2的非携带者 (p <0.005)。此外，UC和CD患者的特征是与对照组相比，IL-1ra等位基因2和IL-1beta等位基因2的关联频率较低 (8.3 vs 20.3% 和10.6 vs 20.3%，p <0.03)。
结论 : 从临床角度来看，IL-1ra和IL-1beta基因多态性分析可能有助于确定UC预后。但是，必须在循环和粘膜水平上进行功能研究，并对等位基因关联进行分层，尤其是IL-1ra等位基因2-IL-1beta等位基因2亚组进行分层，然后才能产生治疗意义。

BACKGROUND & AIMS: :Neuroimmunological diseases often have a chronic course and a high socio-economic impact, as most of them occur in younger patients and result in progressing disability and loss of work force. Although for many conditions different treatment strategies are available no sufficient data exist to give a reasonable account on the cost effectiveness of individual therapies. Treatment decision should primarily be guided by evidence from high quality clinical studies and-if available-from direct head-to-head trials and cost-effectiveness analysis.

背景与目标： : 神经免疫疾病通常具有慢病程和高度的社会经济影响，因为它们大多数发生在年轻患者中，并导致进展中的残疾和劳动力流失。尽管对于许多情况，可以使用不同的治疗策略，但没有足够的数据来合理地说明单个疗法的成本效益。治疗决策应主要以高质量临床研究的证据为指导，如果有的话，应以直接的头对头试验和成本效益分析为指导。

BACKGROUND & AIMS: The hemorheological effects of autologous blood storage with or without the use of erythropoietin were examined before surgery for valvular disease. There was no rheological difference between patients with aortic (16 cases) or mitral (10 cases) valve disease. Before storage, the levels of hematocrit, whole blood viscosity, and especially coefficient of rheology, were lower (p < 0.05) in the blood stored with erythropoietin, but this difference disappeared after storage. The plasma viscosity of both groups did not change before and after storage. The viscosity of blood was equalized after the storage of blood, irrespective of the use of erythropoietin.

背景与目标： 在瓣膜疾病手术前检查了使用或不使用促红细胞生成素的自体血液储存的血液流变学作用。主动脉 (16例) 和二尖瓣 (10例) 瓣膜疾病患者之间的流变学差异无统计学意义。储存前，红细胞压积、全血粘度，特别是流变学系数较低 (p <0.05)，但储存后这种差异消失。两组的血浆粘度在储存前后均无变化。无论使用促红细胞生成素，血液储存后血液的粘度都相等。

BACKGROUND & AIMS: :An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by beta 1-integrins, a subfamily of integrin receptors, formed by the association of the beta 1-chain with different alpha-subunits. To date, no study on alpha-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of alpha-integrin subunits (alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in alpha 1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits alpha 2, alpha 3, and alpha 6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the alpha 1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of alpha 2, alpha 3, and alpha 6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases.

背景与目标： : 细胞/基质相互作用的改变是导致多囊肾疾病中囊肿形成的建议机制之一。这些相互作用中的大多数是由 β1-整合素 (一种整合素受体的亚家族) 介导的，由 β1-链与不同的 α-亚基结合形成。迄今为止，尚无关于囊肿发育早期阶段的 α-整联蛋白亚基分布的研究。使用免疫荧光，我们分析了常染色体显性遗传 (ADPKD) 或常染色体隐性多囊肾 (ARPKD) 胎儿肾脏中 α-整合素亚基 (α1，α2，α3，α5和 α6) 和基底膜蛋白的分布。将分布与正常胎儿和产后肾脏以及胎儿囊性发育不良和梅克尔综合征的分布进行了比较。与正常和囊性对照相比，在两种多囊性疾病 (PKD) 的正常和囊性集合管细胞中观察到 α1-整合素染色显着增加。在PKD和囊性对照的囊肿上皮细胞中，整合素亚基 α2，α3和 α6的分布不规则。在PKD收集导管细胞中特异性观察到的 α1亚基表达增加可能是ARPKD遗传缺陷的早期结果。在ADPKD中，它与pkd1的蛋白质产物多囊蛋白的报道表达相似。在所有类型的囊肿中观察到的 α2，α3和 α6整联蛋白亚基的不规则表达表明，细胞/基质相互作用在早期发生改变，并可能参与囊肿的发展，这可能是通过改变囊性疾病中细胞存活的失调。