精准医学之于阻塞性睡眠呼吸暂停的思考

如今在精准医学研究浪潮的大背景下,睡眠医学也深处其中。然而,相较其他疾病,睡眠呼吸暂停（Obstructive sleep apnea, OSA）这一类疾病似乎更加迫切地需要精准医学的研究思路。本文从OSA的研究发展简述讲起,进一步分析探讨了为何OSA迫切地需要精准医学的研究思路以及如何将精准医学的思路应用于临床OSA的研究。     

下颌后缩畸形矫治术与高血压相关性的研究

目的 探讨下颌后缩畸形矫治术与阻塞性睡眠呼吸暂停(OSA)引起的高血压之间的相关性。方法 对6例下颌后缩畸形且经PSG测试证实为OSA的高血压患者进行手术矫治。结果 6例患者对面形的改善均感满意，晨起血压均有显著下降，其中2例伴有心律失常者的心律恢复正常。结论 下颌后缩畸形矫治术不仅能改善面容及咀嚼功能，且对由OSA引起的高血压，心律失常等有治疗作用。     

下颌前移矫治器对阻塞性睡眠呼吸暂停兔肾皮质的形态学影响

目的 探讨下颌前移矫治器（mandibular advancement device, MAD）治疗阻塞性睡眠呼吸暂停（obstructive sleep apnea, OSA）对兔肾皮质的形态学影响。方法 将18只实验动物随机分为三组，分别为OSA组、MAD组、对照组，每组6只。诱导三组动物仰卧位睡眠4～6小时/天，8周后，切取肾皮质观察显微结构及超微结构。结果 光镜观察：OSA组肾皮质内的肾小管上皮细胞肿胀、变性；肾小球体积显著增大，大量细胞水肿、空化；肾间质纤维化、局限性钙化。MAD组肾小管上皮细胞偶有肿胀，无变性；肾小球体积略增大；肾间质未见纤维化；对照组未见异常。超微结构观察：OSA组近曲小管上皮细胞线粒体肿胀变性、部分空泡化；肾小球足细胞的核染色质凝聚、碎裂，足突出现肿胀和融合。MAD组近曲小管上皮细胞仅有少量线粒体肿胀；肾小球足细胞的核染色质凝聚较少，少量足突肿胀。对照组未见异常。结论 MAD治疗OSA能减缓其对肾皮质的形态学结构损伤。     

口面部肌功能治疗对改善阻塞性睡眠呼吸暂停患儿腺样体扁桃体切除术术后面部形态的影响

目的: 评估口面部肌功能治疗对腺样体扁桃体切除术（adenotonsillectomy,AT）后仍有口呼吸症状的阻塞性睡眠呼吸暂停综合征（obstructive sleep apnea,OSA）患儿面部形态的影响。方法: 纳入10例4~7岁腺样体扁桃体切除术1个月后仍然张口呼吸的OSA患儿,进行口面部肌功能治疗。在口面部肌功能治疗前和治疗结束后6个月,分别拍摄照片,进行软组织测量。选择面部软组织12个具有标志性的点,进行比例和角度测量,采用Graphpad Prism 8 软件进行统计分析,比较口面部肌功能治疗前、后患者面部形态改变。结果: 与治疗前相比,OSA患儿治疗后人中与上唇比例增加（P=0.0002）,上唇与面下1/3比例增加（P<0.05）,鼻唇角增大（P=0.0005）,颏唇角增大（P=0.0026）,面型角减小（P<0.05）。结论: 口面部肌功能治疗能够有效改善OSA患儿AT术后面部形态,可作为OSA患儿AT术后的一种补充治疗,解决患儿术后仍持续存在的张口呼吸问题。     

37．两种下颌前导矫治器治疗阻塞性睡眠呼吸暂停综合征的效果

本研究采用前瞻性、随机交叉实验的方法来评价Twin Block（TB）和Herbst这两种下颌前导矫治器治疗阻塞性睡眠呼吸暂停综合征（OSA）的矫治效果。     

儿童阻塞性睡眠呼吸暂停的诊断和正畸治疗

小儿阻塞性睡眠呼吸暂停(obstructive sleep apnea, OSA)是指患儿在睡眠期间上气道反复发生呼吸阻力增加,气流受阻甚至呼吸暂停。OSA在儿童中的患病率很高,若诊断或治疗不及时会影响患儿的生长发育和生活质量,因此儿童OSA的准确诊断和精确治疗至关重要。儿童OSA的病因复杂多样,目前临床上存在多种诊断方法,其次根据OSA的病因和临床表现的不同可采用的治疗方法也多种多样。近年来,正畸治疗逐渐成为儿童OSA治疗的选择之一,为伴有颅颌面功能和结构异常的患儿提供针对性治疗,在儿童OSA中的应用越来越广泛。本文将就儿童OSA的诊断及正畸治疗进行一综述,以期为正畸治疗儿童OSA提供指导。     

单侧唇裂术后继发鼻畸形的影响因素分析

目的：研究单侧唇裂术后继发鼻畸形的影响因素。方法：收集2005年1月—2006年12月就诊于中国医科大学口腔医院的单侧唇裂术后患者150例,拍摄患者正位、侧位和仰位照片,根据鼻尖、鼻翼、鼻小柱、鼻中隔、鼻背和骨组织畸形程度,对150例患者单侧唇裂术后继发鼻畸形的严重程度进行评价,分为轻度、中度、重度组,筛选性别、患侧、年龄、原有唇裂畸形严重程度、唇裂整复术术式、一期鼻整形术、牙槽突裂和上颌骨发育等因素,应用SPSS13.0软件包分析单侧唇裂术后继发鼻畸形形成中的影响因素。结果：鼻畸形严重程度分组符合评价一致率50%以上患者143例,轻度鼻畸形33例,中度鼻畸形65例,重度鼻畸形45例。性别和患侧对唇裂术后继发鼻畸形无显著影响（P〉0.05）,对唇裂术后继发鼻畸形有影响的因素为年龄（P=0.019）、唇裂严重程度（P=0.000）、唇裂整复术式（P=0.000）、一期鼻整形术（P=0.000）、上颌骨发育（P=0.000）和牙槽突裂（P=0.000）。结论：年龄、原有唇裂畸形的严重程度、唇裂术式选择、一期鼻整形术、上颌骨的发育程度及牙槽突裂是唇裂术后鼻畸形的影响因素。二期鼻整形术前,必须去除上述因素的影响,才能获得理想的术后效果。     

儿童阻塞性睡眠呼吸暂停综合征手术苏醒期疼痛危险因素分析

目的 ：探讨儿童阻塞性睡眠呼吸暂停综合征（obstructive sleep apnea syndrome,OSAS）手术后苏醒期疼痛的危险因素。方法：纳入3—12岁择期行OSAS手术的患儿531例,记录患儿术前焦虑状态、家长焦虑状态、麻醉及手术相关信息、术后躁动及苏醒期疼痛程度,应用多因素Logistic回归分析苏醒期疼痛的危险因素。数据采用SAS 9.4软件进行统计学分析。结果：患儿苏醒期中、重度疼痛发生率为16.6%,年龄（OR=0.85,95%CI:0.76～0.95）、全扁桃体伴或不伴腺样体切除术（OR=1.5,95%CI:1.12～1.99）、术前焦虑（OR=1.01,95%CI:1.00～1.02）、术后躁动（OR=1.22,95%CI:1.17～1.26）及使用氯胺酮（OR=2.59,95%CI:1.53～4.41）与苏醒期疼痛评分独立相关。结论：年龄、全扁桃体伴或不伴腺样体切除术、术前焦虑、术后躁动及使用氯胺酮是儿童OSAS手术后苏醒期疼痛的独立危险因素。     

UPPP术后短期上气道重塑现象的初步探讨

目的 评估腭垂腭咽成形术（uvulopalatopharyngoplasty, UPPP）术前、术后第3天及1、2、3、6个月时上气道及舌骨位置的变化速率,验证UPPP术后短期上气道重塑的现象。方法 选择2013年11月—2014年9月期间于上海交通大学医学院附属第九人民医院就诊并接受UPPP术的21例成年阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者（平均年龄36.58±3.47岁）,术前、术后第3天及1、2、3、6个月时拍摄头颅定位侧位片及"i"音位片。通过AUTOCAD 2015测量,得到各时间点的上气道不同区域（鼻咽、腭咽、舌咽及喉咽气道）前后径及舌骨位置参数（垂直向与水平向）,利用SAS 8.02软件包比较各参数之间的差异,分析评估UPPP术后短期上气道的重塑现象。结果 UPPP术的创伤主要影响腭咽及舌咽气道,腭咽及舌咽参数缩小（P<0.05）,同时UPPP可导致舌骨位置向后下移位（P<0.05）。UPPP术后上气道及舌骨位置参数持续改变,鼻咽气道在术后1~6个月无显著变化（P>0.05）,腭咽气道前后径在术后持续增加（P<0.05）,舌咽气道前后径在术后1月显著增加（P<0.05）。喉咽气道前后径在术后2~6个月逐步减小（P<0.05）,舌骨位置总体向后下下降（P<0.05）,但在术后1个月内舌骨位置处于上升状态（P<0.05）。结论 UPPP术后6个月内上气道存在重塑现象。     

双颌前徙术治疗阻塞性睡眠呼吸暂停低通气综合征及长期稳定性的研究

目的采用双颌前徙术治疗中度到重度的中国阻塞性睡眠呼吸暂停低通气综合征（obstructivesleepapnea-hypopneasyndrome,OSAHS）患者,评估术后效果、治病机理及长期稳定性。方法应用双颌前徙术治疗的中度到重度OSAHS患者共9人。患者分别于T1（术前3个月内）、T2（术后3～6个月）及T3（术后最长随访期,至少1年以上）分别进行多导睡眠图仪检查、拍摄头颅定位侧位x线片进行x线头影测量及三维螺旋CT上气道重建。结果9名患者睡眠呼吸暂停低通气指数（apneaandhypopneaindex,AHI）在T1为49．5次／／l,时,T2为7．8次／小时,T3为8．5次／11,时;睡眠时最低血氧饱和度（10westoxygensaturation,I。SAT）在T1为70．2％,T2为91．8％,T3为90．3％。通过术后长期随访,患者颌骨的位置及上气道各层面的测量值相对稳定,主观症状的改善也表现出很好的稳定性。结论双颌前徙术非常适用于治疗上下颌骨发育不足的OSAHS患者,术后长期随访显示双颔前徘术治疗OSAHS具有较好的长期稳宁件．     

冷常压等离子体处理对纯钛表面性能和成骨细胞增殖迁移的影响研究

目的　研究冷常压等离子体处理后纯钛表面性能变化及对成骨细胞增殖和迁移的影响。方法　本研究于2017年6月至2018年3月在中国医科大学附属口腔医院中心实验室完成。以冷常压等离子体处理后的纯钛片为实验组,未处理的纯钛片作为对照组。（1）通过X射线光电子能谱分析两组钛片表面的化学元素和价键状态,并应用静态接触角测量仪测量两组钛片表面的接触角。（2）通过MTT细胞增殖检测和划痕实验比较两组钛片表面接种的MC3T3-E1成骨细胞增殖和迁移速度。采用SPSS 17.0软件对数据进行统计学分析。结果　（1）实验组钛片表面TiO2和Ti-OH的相对含量百分比较对照组增加;实验组钛片表面的接触角为10.55° ± 0.94°,对照组钛片表面的接触角为46.68° ± 2.77°,两组差异有统计学意义（P < 0.001）,且实验组钛片表面的接触角随着在空气中放置时间的延长而迅速增大,2 h后趋于稳定。（2）实验组钛片表面的MC3T3-E1成骨细胞增殖和迁移速度均明显较对照组快（P < 0.05）。结论　冷常压等离子体处理纯钛片表面后能增加其表面的亲水性,促进成骨细胞的增殖和迁移,可加快种植体植入后与骨组织的整合并促进骨组织的再生,具有重要的临床意义。但冷常压等离子体处理后的纯钛片表面亲水性会在空气中迅速降低,因此须将处理后的种植体立即植入种植窝洞中。     

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??Objective??To study the effects of cold atmospheric plasma on property of pure titanium surface and proliferation and migration of osteoblasts. Methods??This study was performed in Central Laboratory of Affiliated Stomatological Hospital of China Medical University from June 2017 to March 2018. The pure titanium treated with cold atmospheric plasma was taken as the experimental group and the untreated pure titanium as the control group. ??1?? X-ray photoelectron spectroscopy was used to analyze the chemical elements and valence bond states of the two groups of titanium plates??and the contact angle of the two groups of titanium plates was measured by the static contact angle measuring instrument. ??2?? The proliferation and migration of the osteoblasts were compared by MTT cell proliferation detection and scratch test. SPSS17.0 software was used to analyze the data statistically. Results????1?? The relative percentage of TiO2 and Ti-OH on the surface of pure titanium films increased after cold  atmospheric plasma treatment. The contact angle of the pure titanium plate after the cold atmospheric pressure plasma treatment was 10.55° ± 0.94°??and the contact angle of the control group was 46.68° ± 2.77°??and the difference between the two groups was statistically significant??P < 0.001??. Besides??the surface contact angle of the titanium plates of the experimental group increased rapidly with the exposure time in air??which was stable after 2 hours. ??2?? The cell proliferation and cell migration of MC3T3-E1 osteoblasts in the experimental group were significantly faster than in the control group??P < 0.05??. Conclusion??Cold atmospheric plasma on pure titanium surface can increase the hydrophilicity of pure titanium??promote osteoblast proliferation and migration??accelerate the osseointegration after implantation??and promote tissue regeneration. Thus??cold atmospheric plasma has important clinical significance. However??the hydrophilicity of the treated titanium plates decreases rapidly in the air??so the implants should be implanted into the sockets immediately after the cold atmospheric plasma treatment.     

Hydrophilic implants generated using a low-cost dielectric barrier discharge plasma device at the time of placement exhibit increased osseointegration in an animal pre-clinical study: An effect that is sex-dependent

ObjectivesIncreased wettability of titanium and titanium alloy surfaces due to processing and storage methods increases osteoprogenitor cell differentiation and osseointegration compared to microroughness alone. Implants that are exposed to air have a hydrophobic surface due to adsorption of atmospheric hydrocarbons, which can limit overall implant success. Dielectric barrier discharge plasma (DBD) is one method to increase surface hydrophilicity. Although current DBD methods yield a hydrophilic surface, adsorbed hydrocarbons rapidly restore hydrophobicity. We demonstrated that application of DBD to implants previously packaged in a vacuum, generates a hydrophilic surface that supports osteoblastic differentiation in vitro and this can be done immediately prior to use. In the present study, we tested the hypothesis that DBD treatment to alter surface wettability at the time of implant placement will improve osseointegration in vivo.Materials and methodsTwenty male and sixteen female rabbits were used in a preclinical trans-axial femur model of osseointegration. Control and DBD treatment implants were inserted randomized per hind limb in each rabbit (1 implant/hind-limb). At 6 weeks post-surgery, bone-to-implant contact, adjacent bone volume, and torque to failure were assessed by micro-CT, calcified histology, and mechanical testing.ResultsDBD plasma treatment of vacuum-sealed implants increased surface wettability and did not change surface chemistry or roughness. Peak torque and torsional energy, and bone-to-implant contact increased with DBD treatment in males. In contrast, female rabbits showed increased osseointegration equal to DBD treated male implants regardless of DBD plasma treatment.ConclusionDBD treatment is an effective method to enhance osseointegration by increasing surface wettability; however, this response is sex dependent. In healthy female patients, DBD treatment may not be necessary but in older patients or patients with compromised bone, this treatment could be an effective measure to ensure implant success.     

钛种植体表面改性方法

钛种植体具有美观舒适、不损伤邻牙、临床效果显著等优点,广泛应用于口腔种植修复领域;但应用中存在骨结合失败、种植体周围骨吸收、种植体周围炎等问题,使其应用受到一定的限制。对钛种植体进行表面改性,在其表面制备不同的理化涂层和生物活性涂层,可以提高种植体的种植成功率,满足临床应用需求。本文从物理、化学、生物三方面对各种钛种植体表面改性方法的特点进行总结,为牙种植材料的研究和临床应用提供参考。     

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提要：钛和钛合金因具有良好的机械力学性能和生物相容性被广泛用作牙科种植体。种植体植入机体后,与骨的骨性结合是关系到种植体在体内维持时间长短的关键。种植体进入机体后,首先是其表面与组织接触,因此对种植体表面改性是提高种植体与骨的骨性结合的有效方法。本文对目前钛和钛合金表面改性的方法进行简要概述。     

Osseointegration of 3D-printed titanium implants with surface and structure modifications

BackgroundThe purpose of this study was to establish a mechanical and histological basis for the development of biocompatible maxillofacial reconstruction implants by combining 3D-printed porous titanium structures and surface treatment. Improved osseointegration of 3D-printed titanium implants for reconstruction of maxillofacial segmental bone defect could be advantageous in not only quick osseointegration into the bone tissue but also in stabilizing the reconstruction.MethodsVarious macro-mesh titanium scaffolds were fabricated by 3D-printing. Human mesenchymal stem cells were used for cell attachment and proliferation assays. Osteogenic differentiation was confirmed by quantitative polymerase chain reaction analysis. The osseointegration rate was measured using micro computed tomography imaging and histological analysis.ResultsIn three dimensional-printed scaffold, globular microparticle shape was observed regardless of structure or surface modification. Cell attachment and proliferation rates increased according to the internal mesh structure and surface modification. However, osteogenic differentiation in vitro and osseointegration in vivo revealed that non-mesh structure/non-surface modified scaffolds showed the most appropriate treatment effect.Conclusion3D-printed solid structure is the most suitable option for maxillofacial reconstruction. Various mesh structures reduced osteogenesis of the mesenchymal stem cells and osseointegration compared with that by the solid structure. Surface modification by microarc oxidation induced cell proliferation and increased the expression of some osteogenic genes partially; however, most of the markers revealed that the non-anodized solid scaffold was the most suitable for maxillofacial reconstruction.     

经冷常压等离子体处理的纯钛与氧化锆陶瓷粘接强度的实验研究

目的　研究冷常压等离子体处理纯钛,对纯钛微观结构及纯钛与氧化锆陶瓷粘接强度的影响。方法　冷常压等离子体处理纯钛试件不同时间的组均为实验组,不使用冷常压等离子体处理的纯钛试件组作为对照组。分别用接触角测量仪、扫描电子显微镜（SEM）、激光扫描共聚焦显微镜（LSCM）、X射线能谱仪（EDS）、电子万能试验机、体式光学显微镜对纯钛试件表面接触角、表面形貌、元素含量、纯钛与氧化锆陶瓷粘接强度以及粘接断面的断裂模式等进行分析。采用SPSS18.0软件对测量数据进行统计学分析。结果　经冷常压等离子处理的各实验组纯钛与氧化锆陶瓷粘接强度均大于对照组,差异有统计学意义（P < 0.05）;冷常压等离子体处理后的纯钛表面接触角变小,氧元素含量升高,表面粗糙度与形态无明显变化。结论　冷常压等离子体处理纯钛试件能在不改变其表面粗糙度及形貌的情况下,增强表面亲水性,提高表面氧元素含量,从而增强纯钛试件与氧化锆陶瓷试件粘接的强度。这为临床上使用冷常压等离子体处理种植体钛基台后,增强钛基台与氧化锆陶瓷牙冠的粘接强度方面提供了新思路。     

A role for surface topography in creating and maintaining bone at titanium endosseous implants

STATEMENT OF PROBLEM: A variety of claims are made regarding the effects of surface topography on implant osseointegration. Many in vivo and in vitro experimental observations have key limitations in their interpretations. PURPOSE: This review considers the major claims made concerning the effects of commercially pure (cp) titanium implant surface topography on osseointegration. Important findings of consensus are highlighted, and existing controversies are revealed. MATERIAL AND METHODS: This review considers many of the research publications listed in MEDLINE and presented in biomedical research publications and textbooks. RESULTS: Implant surface topography is not well defined in the marketplace or consistently reported among experimental studies. Many in vitro evaluations are not predictive of or correlated with in vivo outcomes. In some culture models, increased surface topography positively affects pro-osteogenic cellular activities. Animal models reveal modest increases in bone-to-implant contact and increases in the biomechanical interlock of the implant with bone for implants of increased surface topography. Existing information fails to define increased surface topography as a risk factor for peri-implant inflammation. CONCLUSION: Increased cp titanium implant surface topography improves the bone-to-implant contact and the mechanical properties of the enhanced interface. Growing clinical evidence for increased bone-to-implant contact at altered cp titanium implants confirms the temporally limited observations made in preclinical studies. In the absence of controlled comparative clinical trials, the aggregate experimental evidence supports the use of cp titanium implants with increased surface topography.     

Temporal sequence of hard and soft tissue healing around titanium dental implants

The objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis‐, angiogenesis‐ and neurogenesis‐associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6–8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.     

Current status of zirconia implants in dentistry: preclinical tests

Purpose

This systematic review aimed to provide an overview of zirconia implants as well as regarding the outcome of the implant-restorative complex in preclinical studies.