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Smokeless tobacco and oral cancer: a review of the risks and determinants. 无烟烟草与口腔癌:风险和决定因素综述。
Brad Rodu, Christer Jansson

Smokeless tobacco has been associated with oral cancer for many decades. The purpose of this article is to review research relevant to this association, including epidemiologic studies, studies of putative carcinogens such as tobacco-specific nitrosamines (TSNAs) and other contaminants, and possible cancer inhibitors. Epidemiologic studies addressing this issue primarily consist of case-control studies. They show that the use of chewing tobacco and moist snuff is associated with very low risks for cancers of the oral cavity and related structures (relative risks [RR] from 0.6 to 1.7). The use of dry snuff is associated with higher RRs, ranging from 4 to 13, while the RRs from smokeless tobacco, unspecified as to type, are intermediate (RR = 1.5 to 2.8). With regard to TSNAs, historical levels in American moist snuff products were higher than those in their Swedish counterparts, but levels in contemporary products are uniformly low. TSNA levels in chewing tobacco have always been low, but levels in dry snuff have been higher, including some very high levels in current products. In general, smokeless tobacco users are not exposed to significant levels of cadmium, lead, benzo(a)pyrene, polonium-210, and formaldehyde, when compared with concentrations of these compounds in foods. Finally, low oral cancer risk from smokeless tobacco use may be influenced by the presence of cancer inhibitors, mainly anti-oxidants, in smokeless tobacco products.

几十年来,人们一直认为无烟烟草与口腔癌有关。本文的目的是回顾与这种关联相关的研究,包括流行病学研究,假定的致癌物,如烟草特异性亚硝胺(TSNAs)和其他污染物的研究,以及可能的癌症抑制剂。针对这一问题的流行病学研究主要包括病例对照研究。他们表明,使用咀嚼烟草和湿鼻烟与患口腔及相关结构癌症的风险非常低(相对风险[RR]从0.6到1.7)。使用干鼻烟的相对危险度较高,介于4至13之间,而无烟烟草的相对危险度为中等(相对危险度= 1.5至2.8),未指明类型。关于tsna,美国湿鼻烟产品的历史水平高于瑞典同类产品,但当代产品的水平一致较低。咀嚼烟草中的TSNA含量一直很低,但干鼻烟中的TSNA含量较高,包括目前产品中的一些非常高的含量。一般来说,与食品中这些化合物的浓度相比,无烟烟草使用者接触到的镉、铅、苯并(a)芘、钋-210和甲醛的含量并不高。最后,无烟烟草使用导致的口腔癌低风险可能受到无烟烟草制品中存在的癌症抑制剂(主要是抗氧化剂)的影响。
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引用次数: 224
Implantology and the severely resorbed edentulous mandible. 种植与重度无牙下颌骨再吸收。
C Stellingsma, A Vissink, H J A Meijer, C Kuiper, G M Raghoebar

Patients with a severely resorbed edentulous mandible often suffer from problems with the lower denture. These problems include: insufficient retention of the lower denture, intolerance to loading by the mucosa, pain, difficulties with eating and speech, loss of soft-tissue support, and altered facial appearance. These problems are a challenge for the prosthodontist and surgeon. Dental implants have been shown to provide a reliable basis for fixed and removable prostheses. This has resulted in a drastic change in the treatment concepts for management of the severely resorbed edentulous mandible. Reconstructive, pre-prosthetic surgery has changed from surgery aimed to provide a sufficient osseous and mucosal support for a conventional denture into surgery aimed to provide a sufficient bone volume enabling implants to be placed at the most optimal positions from a prosthetic point of view. The aim of this paper is to review critically the literature on procedures related to the severely resorbed edentulous mandible and dental implant treatment. The study includes the transmandibular implant, (short) endosseous implants, and reconstructive procedures such as distraction osteogenesis, augmentation of the mandibular ridge with autogenous bone, and bone substitutes followed by the placement of implants. The number of patients participating in a study, the follow-up period, the design of the study, the degree of mandibular resorption, and the survival rate of the dental implants all are considered evaluation parameters. Although numerous studies have described the outcome results of dental implants in the edentulous mandible, there have been few prospective studies designed as randomized clinical trials that compare different treatment modalities to restore the severely resorbed mandible. Therefore, it is not yet possible to select an evidence-based treatment modality. Future research has to be focused on long-term, detailed follow-up clinical trials before scientifically based decisions in treating these patients can be made. This will contribute to a higher level of care in this field.

患者严重吸收无牙下颌骨往往遭受问题与下义齿。这些问题包括:下颌义齿固位不足、黏膜负荷不耐受、疼痛、进食和说话困难、软组织支持丧失和面部外观改变。这些问题对义齿医生和外科医生来说都是一个挑战。牙种植体已被证明为固定和可移动的假体提供了可靠的基础。这导致了严重吸收无牙下颌骨的治疗观念发生了巨大的变化。重建,预修复手术已经从旨在为传统义齿提供足够的骨和粘膜支持的手术转变为旨在提供足够的骨体积,使种植体能够从假肢的角度放置在最佳位置的手术。本文的目的是批判性地回顾文献有关程序的严重吸收无牙下颌骨和种植牙治疗。该研究包括经下颌种植体,(短)骨内种植体和重建手术,如牵张成骨,用自体骨增加下颌嵴,以及骨替代品,然后放置种植体。参与研究的患者人数、随访时间、研究设计、下颌吸收程度、种植体成活率等均被视为评估参数。尽管许多研究描述了无牙下颌骨种植牙的结果,但很少有前瞻性研究设计为随机临床试验,比较不同的治疗方式来恢复严重吸收的下颌骨。因此,尚不可能选择循证治疗方式。未来的研究必须集中在长期、详细的后续临床试验上,然后才能做出基于科学的治疗这些患者的决定。这将有助于提高这一领域的护理水平。
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引用次数: 168
Adverse drug reactions in the orofacial region. 口腔面部的药物不良反应。
C Scully, J-V Bagan

A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed.

广泛的药物有时会引起许多不良的口腔面部表现,特别是口干、味觉障碍、口腔黏膜溃疡和/或牙龈肿胀。该领域的相关随机双盲对照研究很少,因此本文回顾了病例报告、小系列和非同行评议的影响口面部区域药物不良反应的报告(可从MEDLINE检索到2003年4月)。讨论了药物治疗更常见和显著的不良口腔面部后果。
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引用次数: 249
Chemotaxis-guided movements in bacteria. 趋化引导的细菌运动。
Renate Lux, Wenyuan Shi

Motile bacteria often use sophisticated chemotaxis signaling systems to direct their movements. In general, bacterial chemotactic signal transduction pathways have three basic elements: (1) signal reception by bacterial chemoreceptors located on the membrane; (2) signal transduction to relay the signals from membrane receptors to the motor; and (3) signal adaptation to desensitize the initial signal input. The chemotaxis proteins involved in these signal transduction pathways have been identified and extensively studied, especially in the enterobacteria Escherichia coli and Salmonella enterica serovar typhimurium. Chemotaxis-guided bacterial movements enable bacteria to adapt better to their natural habitats via moving toward favorable conditions and away from hostile surroundings. A variety of oral microbes exhibits motility and chemotaxis, behaviors that may play important roles in bacterial survival and pathogenesis in the oral cavity.

活动细菌通常使用复杂的趋化信号系统来指导它们的运动。一般来说,细菌趋化信号转导途径有三个基本要素:(1)位于膜上的细菌趋化受体接受信号;(2)信号转导,将膜受体的信号传递到马达;(3)信号自适应,对初始信号输入进行脱敏。参与这些信号转导途径的趋化蛋白已经被发现并进行了广泛的研究,特别是在大肠杆菌和肠炎沙门氏菌血清型鼠伤寒杆菌中。趋化引导的细菌运动使细菌能够更好地适应其自然栖息地,通过向有利条件移动,远离不利环境。多种口腔微生物表现出运动性和趋化性,这些行为可能在口腔细菌的生存和发病机制中发挥重要作用。
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引用次数: 84
The embryonic origins of left-right asymmetry. 左右不对称的胚胎起源。
Michael Levin

The bilaterally symmetric body plan of vertebrates features several consistent asymmetries in the placement, structure, and function of organs such as the heart, intestine, and brain. Deviations from the normal pattern result in situs inversus, isomerisms, or heterotaxia (independent randomization), which have significant clinical implications. The invariance of the left-right (LR) asymmetry of normal morphology, neuronal function, and phenotype of several syndromes raises fascinating and fundamental questions in cell, developmental, evolutionary, and neurobiology. While a pathway of asymmetrically expressed signaling factors has been well-characterized in several model systems, very early steps in the establishment of LR asymmetry remain poorly understood. In particular, the origin of consistently oriented asymmetry is unknown. Recently, a candidate for the origins of asymmetry has been suggested: bulk transport of extracellular morphogens by rotating primary cilia during gastrulation. This model is appealing because it 'bootstraps' morphological asymmetry of the embryo from the intrinsic structural (molecular) chirality of motile cilia. However, conceptual and practical problems remain with this hypothesis. Indeed, the genetic data are also consistent with a different mechanism: cytoplasmic transport roles of motor proteins. This review outlines the progress and remaining questions in the field of left-right asymmetry, and focuses on an alternative model for 'Step 1' of asymmetry. More specifically, based on wide-ranging data on ion fluxes and motor protein function in several species, it is suggested that laterality is driven by pH/voltage gradients across the midline, which are established by chiral movement of motor proteins with respect to the cytoskeleton.

脊椎动物的身体两侧对称,在心脏、肠和脑等器官的位置、结构和功能上有几个一致的不对称。偏离正常模式会导致位置反转、异构体或异位(独立随机化),这具有重要的临床意义。几种综合征的正常形态、神经元功能和表型的左右(LR)不对称的不变性,在细胞、发育、进化和神经生物学中提出了引人入胜的基本问题。虽然不对称表达的信号因子的途径已经在几个模型系统中得到了很好的表征,但对LR不对称建立的早期步骤仍然知之甚少。特别是,持续定向不对称的起源是未知的。最近,不对称的一个候选来源被提出:在原肠形成过程中,通过旋转初级纤毛大量运输细胞外形态因子。这个模型很有吸引力,因为它从运动纤毛的内在结构(分子)手性中“引导”了胚胎的形态不对称。然而,这一假设仍然存在概念和实际问题。事实上,遗传数据也与另一种不同的机制一致:运动蛋白的细胞质运输作用。本文概述了左右不对称领域的进展和存在的问题,并重点介绍了不对称“第一步”的替代模型。更具体地说,基于对几种物种中离子通量和运动蛋白功能的广泛数据,表明偏侧性是由穿过中线的pH/电压梯度驱动的,这是由运动蛋白相对于细胞骨架的手性运动建立的。
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引用次数: 70
The role of human papillomavirus in oral carcinogenesis. 人乳头瘤病毒在口腔癌发生中的作用。
Patrick K Ha, Joseph A Califano

Human papillomavirus (HPV) infection with high-risk types 16 and 18 has widely been reported as one of the prominent mechanisms behind the development of cervical squamous cell carcinoma. Links between HPV and oral cavity cancer have been suggested as well, based on epidemiologic and molecular means, though the association is less well-established. It is likely that HPV plays a role in oral cavity carcinogenesis, though only in a small subset of cases. The difficulty in providing true causal evidence of HPV's role in oral cancer lies in our lack of understanding of the significance of mechanisms by which HPV leads to oral carcinogenesis, as well as limitations in the molecular analysis of HPV. Further studies are necessary for the contribution of HPV in oral cavity malignancy to be better demonstrated.

人类乳头瘤病毒(HPV)感染的高危型16和18已被广泛报道为宫颈鳞状细胞癌发展背后的重要机制之一。基于流行病学和分子手段,HPV和口腔癌之间的联系也被提出,尽管这种联系还不太确定。HPV很可能在口腔癌变中起作用,尽管只在一小部分病例中起作用。提供HPV在口腔癌中作用的真正因果证据的困难在于我们缺乏对HPV导致口腔癌发生机制的重要性的理解,以及HPV分子分析的局限性。HPV在口腔恶性肿瘤中的作用需要进一步的研究来更好地证明。
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引用次数: 162
Altered autoantigen structure in Sjögren's syndrome: implications for the pathogenesis of autoimmune tissue damage. Sjögren综合征的自身抗原结构改变:自身免疫组织损伤的发病机制
A Rosen, L Casciola-Rosen

The etiology and pathogenic mechanisms underlying Sjögren's syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.

Sjögren综合征(SS)的病因学和发病机制尚不清楚。最近的研究强调,在SS患者中高比例出现的特异性自身抗体可能为该疾病中引发和传播组织损伤的情况提供了重要的见解。尽管针对全身性自身免疫性疾病的自身抗原在正常细胞中的结构、亚细胞分布或功能方面几乎没有共同点,但这些分子通过聚集和集中在凋亡细胞的表面泡中而统一起来。此外,它们的结构在某些类型的细胞死亡过程中发生改变,以产生以前在发育和体内平衡过程中没有产生的结构。本文综述了SS自身抗原在免疫效应通路激活过程中对这些结构变化的易感性,并综合了一个包含这些概念的SS模型。了解SS中特异性免疫反应的激活机制,以及特异性免疫效应通路在自身免疫反应和组织损伤传播中的作用,具有潜在的治疗意义。本文使用的缩写是:CTL,细胞毒性t淋巴细胞;内质网;谷氨酸受体III亚基GluR3;GrB,颗粒酶B;M3R, III型毒蕈碱受体;NK细胞,自然杀伤细胞;PARP,保利(ADP-ribose)聚合酶;SS, Sjögren综合征;系统性红斑狼疮;UV,紫外线。
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引用次数: 45
Efficacy and co-morbidity of oral appliances in the treatment of obstructive sleep apnea-hypopnea: a systematic review. 口腔矫治器治疗阻塞性睡眠呼吸暂停低通气的疗效和合并症:一项系统综述。
A Hoekema, B Stegenga, L G M De Bont

The Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a common sleep-related breathing disorder characterized by repetitive obstructions of the upper airway during sleep. Modification of pharyngeal patency by Oral Appliance (OA) therapy has been suggested as an alternative to various treatment modalities for OSAHS. To determine the evidence base with respect to the efficacy and co-morbidity of OA therapy in OSAHS, we conducted a systematic review of the available literature. Primary outcome measures were the reduction in number of upper-airway obstructions and co-morbidity related to the craniomandibular or craniofacial complex, respectively. Eligible studies regarding efficacy were independently assessed by two assessors using a quality assessment scale. Effect sizes of methodologically sound studies were calculated. In identical interventions, effect sizes were pooled with the use of a random-effects model. Given the scarcity of controlled studies related to co-morbidity, appraisal was confined to a description of eligible studies. Sixteen controlled trials related to efficacy were identified. With respect to the primary outcome measure, OA therapy was clearly more effective than control therapy (pooled effect size, -0.96; 95% confidence interval [CI], -1.49 to -0.42) and possibly more effective than uvulopalatopharyngoplasty. Although patients generally preferred OA therapy, improvement of respiratory variables, such as the number of upper-airway obstructions, was usually better in Continuous Positive Airway Pressure (CPAP) therapy (pooled effect size, 0.83; 95% CI, 0.59 to 1.06). Moreover, specific aspects related to OA design may influence patient-perceived efficacy and preference. Twelve patient-series and one controlled trial related to co-morbidity were identified. Analysis of the data suggests that OA therapy may have adverse effects on the craniomandibular and craniofacial complex. Although CPAP is apparently more effective and adverse effects of OA treatment have been described, it can be concluded that OA therapy is a viable treatment for, especially, mild to moderate OSAHS. Controlled studies addressing the specific indication and co-morbidity of OA therapy are warranted.

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是一种常见的睡眠相关呼吸障碍,其特征是睡眠期间反复出现上呼吸道阻塞。通过口腔矫治器(OA)治疗来改善咽通畅已被建议作为OSAHS各种治疗方式的替代方案。为了确定OA治疗OSAHS的疗效和合并症的证据基础,我们对现有文献进行了系统回顾。主要结局指标是上呼吸道阻塞数量的减少,以及分别与颅颌部或颅面复合体相关的合并症。关于疗效的合格研究由两名评估员使用质量评估量表独立评估。计算了方法学上可靠的研究的效应量。在相同的干预措施中,效应大小通过使用随机效应模型进行汇总。由于缺乏与合并症相关的对照研究,评价仅限于对符合条件的研究的描述。确定了16项与疗效相关的对照试验。关于主要结局指标,OA治疗明显比对照治疗更有效(合并效应值,-0.96;95%可信区间[CI], -1.49至-0.42),可能比悬雍垂腭咽成形术更有效。尽管患者通常更倾向于OA治疗,但持续气道正压(CPAP)治疗通常能更好地改善呼吸变量,如上气道阻塞的数量(合并效应值,0.83;95% CI, 0.59 ~ 1.06)。此外,与OA设计相关的特定方面可能会影响患者感知的疗效和偏好。确定了与合并症相关的12个患者系列和1个对照试验。数据分析表明OA治疗可能对颅下颌和颅面复合体有不良影响。虽然CPAP显然更有效,并且已经描述了OA治疗的不良反应,但可以得出结论,OA治疗是一种可行的治疗方法,特别是轻中度OSAHS。针对OA治疗的具体适应症和合并症的对照研究是有必要的。
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引用次数: 168
Alternatives in polymerization contraction stress management. 聚合收缩应力管理的替代方案。
R R Braga, J L Ferracane

Polymerization contraction stress of dental composites is often associated with marginal and interfacial failures of bonded restorations. The magnitude of stress depends on composite composition (filler content and matrix composition) and its ability to flow before gelation, which is related to the cavity configuration and curing characteristics of the composite. This article reviews variations among studies regarding contraction-stress-testing methods and contraction stress values of current composites, and discusses the validity of contraction stress studies in relation to results from microleakage tests. The effects of lower curing rates and alternative curing routines on contraction stress values are also discussed, as well as the use of low-elastic-modulus liners. Moreover, studies with experimental dimethacrylate-based composites and recent developments in low-shrinkage monomers are described.

牙科复合材料的聚合收缩应力通常与粘结修复体的边缘和界面失效有关。应力的大小取决于复合材料成分(填料含量和基体成分)及其在凝胶化前的流动能力,这与复合材料的空腔结构和固化特性有关。本文综述了当前复合材料收缩应力测试方法和收缩应力值研究的差异,并讨论了收缩应力研究与微泄漏试验结果的有效性。还讨论了较低的固化速率和替代固化程序对收缩应力值的影响,以及低弹性模量衬垫的使用。此外,还介绍了实验二甲基丙烯酸酯基复合材料的研究和低收缩单体的最新进展。
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引用次数: 224
Post-translational modifications of sibling proteins and their roles in osteogenesis and dentinogenesis. 兄弟蛋白的翻译后修饰及其在成骨和牙本质发生中的作用。
C Qin, O Baba, W T Butler

The extracellular matrix (ECM) of bone and dentin contains several non-collagenous proteins. One category of non-collagenous protein is termed the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, that includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE). These polyanionic SIBLING proteins are believed to play key biological roles in the mineralization of bone and dentin. Although the specific mechanisms involved in controlling bone and dentin formation are still unknown, it is clear that some functions of the SIBLING family members are dependent on the nature and extent of post-translational modifications (PTMs), such as phosphorylation, glycosylation, and proteolytic processing, since these PTMs would have significant effects on their structure. OPN and BSP are present in the ECM of bone and dentin as full-length forms, whereas amino acid sequencing indicates that DMP1 and DSPP exist as proteolytically processed fragments that result from scission of X-Asp bonds. We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue. We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets.

骨和牙本质的细胞外基质(ECM)含有几种非胶原蛋白。一类非胶原蛋白被称为兄弟蛋白(小整合素结合配体,n-连接糖蛋白)家族,包括骨桥蛋白(OPN),骨唾液蛋白(BSP),牙本质基质蛋白1 (DMP1),牙本质唾液蛋白(DSPP)和基质细胞外磷酸糖蛋白(MEPE)。这些多阴离子兄弟蛋白被认为在骨和牙本质的矿化中起着关键的生物学作用。虽然控制骨和牙本质形成的具体机制尚不清楚,但很明显,兄弟姐妹家族成员的一些功能依赖于翻译后修饰(PTMs)的性质和程度,如磷酸化、糖基化和蛋白水解加工,因为这些PTMs会对其结构产生重大影响。OPN和BSP以全长形式存在于骨和牙本质的ECM中,而氨基酸测序表明DMP1和DSPP以X-Asp键断裂产生的蛋白水解片段存在。我们假设DMP1和DSPP的加工是由PHEX酶催化的,因为这种蛋白是一种主要在骨骼和牙齿中表达的内肽酶,在天冬氨酸残基的nh2端具有强烈的裂解偏好。我们设想DMP1和DSPP的蛋白水解过程可能是一个激活过程,在骨形成和牙本质形成中起着重要的关键作用,并且该过程的失败将导致骨和牙本质矿化缺陷,正如在x连锁低磷血症佝偻病中观察到的那样。
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引用次数: 422
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