BACKGROUND & AIMS: BACKGROUND:Patients who have pain and dysfunction from glenohumeral arthritis associated with severe rotator cuff deficiency have few treatment options. The goal of this study was to retrospectively evaluate the short-term results of arthroplasty with use of the Reverse Shoulder Prosthesis in the management of this problem. METHODS:We report the results for sixty patients (sixty shoulders) with a rotator cuff deficiency and glenohumeral arthritis who were followed for a minimum of two years. Thirty-five patients had no previous shoulder surgery, whereas twenty-three had had either an open or arthroscopic rotator cuff repair, one had had a subacromial decompression, and one had had a biceps tendon repair. All patients were assessed preoperatively and postoperatively with the American Shoulder and Elbow Surgeons scoring system for pain and function and with visual analog scales for pain and function. They were also asked to rate their satisfaction with the outcome. The shoulder range of motion was measured preoperatively and postoperatively. RESULTS:The average age of the patients was seventy-one years. The average duration of follow-up was thirty-three months. All measures improved significantly (p < 0.0001). The mean total score on the American Shoulder and Elbow Surgeons system improved from 34.3 to 68.2; the mean function score, from 16.1 to 29.4; and the mean pain score, from 18.2 to 38.7. The score for function on the visual analog scale improved from 2.7 to 6.0, and the score for pain on the visual analog scale improved from 6.3 to 2.2. Forward flexion increased from 55.0 degrees to 105.1 degrees , and abduction increased from 41.4 degrees to 101.8 degrees . Forty-one of the sixty patients rated the outcome as good or excellent; sixteen were satisfied, and three were dissatisfied. There were a total of thirteen complications in ten patients (17%). Seven patients (12%) had eight failures, requiring revision surgery to another Reverse Shoulder Prosthesis in five patients (one shoulder had two revisions) and revision to a hemiarthroplasty in two patients because of deep infection. CONCLUSIONS:The data from this study suggest that arthroplasty with the Reverse Shoulder Prosthesis may be a viable treatment for patients with glenohumeral arthritis and a massive rotator cuff tear. However, future studies will be necessary to determine the longevity of the implant and whether it will provide continued improvement in function.

背景与目标： 背景：患有因严重肩袖缺损而引起的盂肱型关节炎引起的疼痛和功能障碍的患者几乎没有治疗选择。这项研究的目的是回顾性评估使用反向肩假体治疗该问题的关节置换术的短期结果。
方法：我们报告了60例肩袖缺损和盂肱型关节炎患者的结果，这些患者至少随访了两年。 35例患者以前没有进行过肩部手术，而23例患者进行了开放式或关节镜下肩袖修复，1例行肩峰下减压，1例进行了二头肌腱修复。所有患者在术前和术后均通过American Shoulder and Elbow Surgeons疼痛和功能评分系统进行评估，并使用视觉模拟量表评估疼痛和功能。他们还被要求对结果表示满意。术前和术后测量肩膀的运动范围。
结果：患者的平均年龄为71岁。平均随访时间为三十三个月。所有措施均显着改善（p <0.0001）。美国肩肘外科医师系统的平均总得分从34.3提高到68.2；平均功能评分从16.1至29.4；平均疼痛评分从18.2至38.7。视觉模拟量表上的功能评分从2.7提高到6.0，视觉模拟量表上的疼痛评分从6.3提高到2.2。前屈从55.0度增加到105.1度，外展从41.4度增加到101.8度。 60例患者中有41例的结局为好或差。十六个人满意，三个人不满意。 10例患者中共有13例并发症（17％）。 7例患者（占12％）有8例失败，由于深部感染，需要对5例患者的另一个反向肩假体进行翻修手术（其中一个肩膀进行了2次翻修），并且对2例患者进行了半髋置换术翻修。
结论：这项研究的数据表明，带肩关节假体的人工关节置换术可能是对盂肱型关节炎和巨大的肩袖撕裂患者的一种可行的治疗方法。但是，未来的研究对于确定植入物的寿命以及是否能够持续改善其功能将是必要的。

BACKGROUND & AIMS: :Varus posteromedial rotatory instability refers to one of the complex elbow fracture-dislocation caused by anteromedial coronoid fracture with disruption of lateral collateral ligament (LCL). Recent clinical and biomechanical studies have demonstrated that this unstable complex injury resulted in incongruence of joint, which could lead to early posttraumatic arthritis. With reports of poor result after conservative treatment, surgical treatment including anteromedial fixation and LCL repair has been strongly recommended to achieve stable joint. This case series describes three patients with anteromedial coronoid fracture who were managed conservatively with excellent outcomes. This report suggests that anteromedial coronoid fracture associated with posteromedial rotatory instability might be treated using conservative treatment in selective cases when anteromedial coronoid fracture is minimally displaced and there is no evidence of elbow subluxation.

背景与目标： ：内翻后内侧旋转不稳是指由冠状动脉前内侧骨折伴侧副韧带（LCL）破坏引起的复杂肘部骨折脱位之一。最近的临床和生物力学研究表明，这种不稳定的复杂损伤导致关节不协调，这可能导致创伤后早期关节炎。有报道称保守治疗后效果不佳，强烈建议进行外科手术治疗，包括前路内固定和LCL修复，以实现稳定的关节。本病例系列描述了三例冠状动脉前内侧骨折患者，保守治疗均取得了良好的效果。该报告表明，在选择性病例中，当前冠状动脉内侧骨折移位最小且没有肘关节半脱位的证据时，可以采用保守治疗来治疗前内侧旋转不稳定性伴有前内侧冠状动脉骨折。

BACKGROUND & AIMS: :Microsatellite instability (MSI) has been reported in 25% to 45% of sporadic endometrial carcinoma. The clinicopathologic and molecular characteristics of MSI-high phenotype in colorectal and gastric carcinomas have been widely investigated; however, the clinicopathologic impact of MSI on endometrial carcinomas remained unclear. This study was performed to determine the clinicopathologic and molecular significance of MSI in endometrial carcinomas. We analyzed the MSI status using National Cancer Institute-recommended 5 microsatellite markers, and the immunohistochemical profiles of various regulatory proteins of cell cycle and apoptosis using tissue microarray in 100 endometrial carcinomas. The results were compared between MSI-high and MSI(-) groups as for the traditional clinicopathologic prognostic parameters and the immunoreactivities of various regulatory proteins. We especially focused on the endometrioid type adenocarcinoma to exclude the bias from nonendometrioid type adenocarcinomas with more aggressiveness and a close association with MSI(-) phenotype. The incidence of MSI-high phenotype was significantly higher in endometrioid type than in nonendometrioid serous type (20% vs. 0%, P<0.001). It showed orderly increase in the frequencies of MSI-high phenotype in higher histologic grade (13% vs. 21% vs. 50% in histologic grade I, II, and III, P=0.039). The MSI-high phenotype was related with the presence of lymphovascular invasion (P=0.008), deep myometrial invasion (P=0.040), and the higher clinical stages (P=0.018) independent of tumor grade. We also found a correlation between MSI-high phenotype and higher cyclin A and skp2 immunoreactivity (P=0.03 and 0.05, respectively), known to be the poor prognostic molecular indicators. According to these results, the MSI may represent the poor prognostic impact on the endometrioid type endometrial adenocarcinoma.

背景与目标： ：已有25％至45％的散发性子宫内膜癌报道了微卫星不稳定性（MSI）。 MSI高表型在大肠癌和胃癌中的临床病理和分子特征已得到广泛研究；然而，MSI对子宫内膜癌的临床病理影响尚不清楚。进行这项研究以确定MSI在子宫内膜癌中的临床病理和分子意义。我们使用美国国家癌症研究所推荐的5种微卫星标记分析了MSI状态，并使用组织芯片分析了100种子宫内膜癌中细胞周期和凋亡的各种调节蛋白的免疫组织化学特征。将MSI高组和MSI（-）组之间的结果进行比较，以了解传统的临床病理预后参数和各种调节蛋白的免疫反应性。我们特别关注子宫内膜样腺癌，以排除具有更强侵略性且与MSI（-）表型密切相关的非子宫内膜样腺癌的偏倚。子宫内膜样类型的MSI-高表型的发生率显着高于非子宫内膜样浆液性（20％vs. 0％，P <0.001）。在较高的组织学等级中，显示MSI-高表型的频率有序增加（在组织学等级I，II和III中，分别为13％对21％和50％，P = 0.039）。 MSI-高表型与淋巴管浸润（P = 0.008），深层子宫肌层浸润（P = 0.040）以及较高的临床分期（P = 0.018）有关，而与肿瘤分级无关。我们还发现了MSI高表型与较高的细胞周期蛋白A和skp2免疫反应性之间的相关性（分别为P = 0.03和0.05），这被认为是不良的预后分子指标。根据这些结果，MSI可能代表对子宫内膜样型子宫内膜腺癌的不良预后影响。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the diagnostic yield of two acquisitions of single-contrast CT arthrography (CTA) of the shoulder in internal, neutral, or external glenohumeral rotation with arthroscopic correlation. MATERIALS AND METHODS:The CT study was obtained using two acquisitions (first the humerus positioned in maximum tolerated external rotation with the arm along the body and the second with the humerus in internal rotation with the palm placed flat on the table). Two independent readers blinded to the arthroscopic results evaluated the CTA images for labral tears, glenoid bone loss/fractures, and cartilage loss. For each CTA acquisition, sensitivity and specificity for detection of the aforementioned pathology were assessed. Inter-reader agreement was quantified by weighted ĸ statistics. RESULTS:Sensitivity and specificity for detecting anteroinferior or posterior labral tears was highest with neutral rotation (sensitivity 91-100%, specificity 61-100%). For glenoid fracture, sensitivity (67%) was highest with external rotation and specificity (100%) was highest with internal rotation. For cartilage loss, sensitivity (64%) and specificity (89%) was highest with external rotation and neutral rotation, respectively. Neutral rotation showed high sensitivity and specificity for glenoid fractures and cartilage loss. Inter-reader agreement ranged from fair to very good. CONCLUSIONS:Neutral glenohumeral position in shoulder CT arthrography was adequately sensitive and specific for the detection of intra-articular pathology, avoiding the use of more than one acquisition.

背景与目标： 目的：通过关节镜相关性评估两次获取的单次CT单次CT造影（CTA）在内部，中性或外部盂肱旋转中的诊断价值。
材料与方法：CT研究是通过两次采集获得的（首先，肱骨在手臂沿身体的最大允许外旋中定位，第二步在肱骨内旋转且手掌平放在桌子上的状态下进行肱骨旋转）。两名不愿接受关节镜检查结果的独立读者评估了CTA图像的唇裂，盂盂骨丢失/骨折和软骨丢失。对于每次CTA采集，评估用于检测上述病理的敏感性和特异性。读者间的一致性通过加权统计来量化。
结果：中性旋转时，检出前下唇或后唇撕裂的敏感性和特异性最高（敏感性为91-100％，特异性为61-100％）。对于关节盂骨折，外旋敏感性最高（67％），内旋特异性最高（100％）。对于软骨损失，外旋和中性旋转分别具有最高的敏感性（64％）和特异性（89％）。中性旋转显示出对关节盂骨折和软骨损失的高敏感性和特异性。读者间的协议范围从公平到非常好。
结论：肩部CT关节造影中的肱骨肱中位对于检测关节内病变具有足够的敏感性和特异性，避免了多次采集。

BACKGROUND & AIMS: :Using x-ray magnetic spectroscopy with in-situ electrical characterizations, we investigated the effects of external voltage on the spin-electronic and transport properties at the interface of a Fe/ZnO device. Layer-, element-, and spin-resolved information of the device was obtained by cross-tuning of the x-ray mode and photon energy, when voltage was applied. At the early stage of the operation, the device exhibited a low-resistance state featuring robust Fe-O bonds. However, the Fe-O bonds were broken with increasing voltage. Breaking of the Fe-O bonds caused the formation of oxygen vacancies and resulted in a high-resistance state. Such interface reconstruction was coupled to a charge-transfer effect via Fe-O hybridization, which suppressed/enhanced the magnetization/coercivity of Fe electronically. Nevertheless, the interface became stabilized with the metallic phase if the device was continuously polarized. During this stage, the spin-polarization of Fe was enhanced whereas the coercivity was lowered by voltage, but changes of both characteristics were reversible. This stage is desirable for spintronic device applications, owing to a different voltage-induced electronic transition compared to the first stage. The study enabled a straightforward detection of the spin-electronic state at the ferromagnet-semiconductor interface in relation to the transport and reversal properties during operation process of the device.

背景与目标： ：使用具有原位电学特征的X射线电磁光谱技术，我们研究了外部电压对Fe / ZnO器件界面处的自旋电子和输运性质的影响。当施加电压时，通过交叉调整X射线模式和光子能量，可以获得设备的层，元素和自旋分辨信息。在操作的早期阶段，该器件表现出具有坚固的Fe-O键的低电阻状态。然而，随着电压的升高，Fe-O键断裂。 Fe-O键的断裂导致氧空位的形成并导致高电阻状态。这种界面重建通过Fe-O杂化作用耦合到电荷转移效应，从而电子地抑制/增强了Fe的磁化/矫顽力。但是，如果器件连续极化，则界面会被金属相稳定。在此阶段，铁的自旋极化增强，而矫顽力由于电压而降低，但两种特性的变化都是可逆的。由于与第一阶段相比，电压感应的电子跃迁不同，因此该阶段对于自旋电子设备应用是理想的。这项研究使得能够在设备操作过程中直接检测铁磁-半导体界面上的自旋电子状态与传输和反转特性之间的关系。

BACKGROUND & AIMS: Cytogenetic study in a case of a human chromophobe renal cell carcinoma revealed a hypodiploid chromosome number of 36 with loss of chromosomes 1, 2, 5, 6, 10, 13, 15, 17, 21, and X. The tumor DNA showed microsatellite instability in dinucleotide repeat microsatellite markers. This is the fourth case that has been fully karyotyped and showed a low chromosome number in a chromophobe renal cell carcinoma. Our data in the present study are consistent with those in the literature. It is suggested that human chromophobe renal cell carcinoma may possibly be characterized by tumor cells with low chromosome number or microsatellite instability.

背景与目标： 在人类发色团肾细胞癌病例中进行的细胞遗传学研究显示，二倍体染色体数为36，缺失了1、2、5、6、10、13、15、17、21和X染色体。肿瘤DNA显示微卫星不稳定性在二核苷酸中重复微卫星标记。这是第四例完全染色体核型，并且在发色肾细胞癌中显示出低染色体数。我们在本研究中的数据与文献中的一致。提示人类发色团肾细胞癌的特征可能在于低染色体数或微卫星不稳定性的肿瘤细胞。

BACKGROUND & AIMS: BACKGROUND:Chronic ankle instability (CAI) induces osteoarthritis (OA) by inflicting abnormal stresses on the medial gutter. It is important to detect early OA change and to explore factors likely to induce the OA. The purpose of this study was to evaluate subchondral bone change in the medial gutter of CAI using computed tomography (CT) scans. METHODS:Thirty-five ankles with CAI (CAI group) and 35 ankles without CAI (control group) were included. The region of interest (ROI) in the subchondral bone of the medial gutter on CT axial images was set on the tibia and talus. The Hounsfield unit (HU) in ROIs was measured and corrected by the HU of the fibula in the same slice. HU ratios were compared between the CAI and control groups. In the CAI group, the relationship between the HU ratio and the talar tilt angle (TTA), OA change, and the anterior talofibular ligament (ATFL) remnant quality were analyzed. RESULTS:The mean HU ratio in the CAI group was significantly higher than that in the control. In the CAI group, HU ratios in ≥10 degrees of TTA were significantly higher than those in <10 degrees. But there was no significant difference in the HU ratios with or without OA change in the medial gutter. A good-quality ATFL remnant showed a low HU ratio compared with that with poor quality. CONCLUSION:CAI patients exhibited subchondral bone change in the medial gutter, which suggests that the elimination of instability may help to prevent or decrease the development and/or progression of osteoarthritis. LEVEL OF EVIDENCE:Level III, comparative series.

背景与目标： 背景：慢性踝关节不稳（CAI）通过对内侧水槽施加异常压力来诱发骨关节炎（OA）。重要的是要发现早期OA的变化并探讨可能诱发OA的因素。这项研究的目的是使用计算机断层扫描（CT）扫描评估CAI内侧沟中软骨下骨的变化。
方法：包括35只CAI踝关节（CAI组）和35只无CAI踝关节（对照组）。在CT轴向图像上，内侧沟槽的软骨下骨中的感兴趣区域（ROI）设置在胫骨和距骨上。通过相同切片中腓骨的HU来测量和校正ROI中的Hounsfield单位（HU）。比较了CAI组和对照组之间的HU比率。在CAI组中，分析了HU比与距骨倾斜角（TTA），OA变化和距前腓韧带（ATFL）残留质量之间的关系。
结果：CAI组的平均HU比值显着高于对照组。在CAI组中，TTA≥10度的HU比明显高于<10度的HU。但是，无论有无内沟OA改变，HU比率均无显着差异。优质的ATFL残余物与低劣的质量相比显示出较低的HU比率。
结论：CAI患者的内侧沟软骨下骨改变，提示不稳定性的消除可能有助于预防或减少骨关节炎的发展和/或发展。
证据水平：III级，比较系列。

BACKGROUND & AIMS: :Microsatellite instability (MSI) in human carcinoma DNA is a characteristic phenotype observed in hereditary non-polyposis colorectal cancer and also in some human sporadic cancers including multiple primary carcinomas. In this study, we analyzed mutations in the hCHK1, E2F4, hMSH3, and hMSH6 genes in MSI+ human cancers arising in colorectum, stomach and endometrium. The E2F4 and hMSH3 genes were mutated in all tumor types. Interestingly, the hMSH6 gene was mutated in colorectal and gastric cancers but not in endometrial cancer; this is similar to the TGFbetaRII gene. It is notable that the mutation status of the secondary mutators, hMSH3 and hMSH6, did not influence slippage-related frameshift mutations in genes harboring simple tandem-repeats, which suggests that the MSI phenotype may be affected mainly by abnormalities in the primary mutator genes, not by the secondary mutator genes. No mutations were observed in the cell cycle checkpoint gene hCHK1; mutations of this gene are thought to have a limited role, if any, in at least the tumor types analyzed in this study.

背景与目标： ：人类癌症DNA中的微卫星不稳定性（MSI）是在遗传性非息肉性结直肠癌以及某些人类散发性癌症（包括多种原发癌）中观察到的特征表型。在这项研究中，我们分析了MSI人类癌症中由结直肠，胃和子宫内膜引起的hCHK1，E2F4，hMSH3和hMSH6基因突变。 E2F4和hMSH3基因在所有肿瘤类型中均发生突变。有趣的是，hMSH6基因在大肠癌和胃癌中发生了突变，而在子宫内膜癌中没有发生突变。这类似于TGFbetaRII基因。值得注意的是，二级突变体hMSH3和hMSH6的突变状态不会影响具有简单串联重复序列的基因中与滑移相关的移码突变，这表明MSI表型可能主要受一级突变体基因的异常影响，而不是由次级突变基因。在细胞周期检查点基因hCHK1中未观察到突变。该基因的突变至少在本研究中分析的肿瘤类型中被认为具有有限的作用（如果有的话）。

BACKGROUND & AIMS: OBJECTIVES:To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo. PATIENTS AND METHODS:In all, 208 patients were allocated at random to either TCl or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy. RESULTS:Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one-sided P = 0. 0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one-sided P = 0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two-sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group). CONCLUSION:Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.

背景与目标： 目的：与安慰剂相比，评估氯化钾（TC1，每天两次，每次20 mg）在治疗逼尿肌不稳中的疗效和安全性。
病人和方法：在一项双盲临床研究中，共有208名患者被随机分配为TCl或安慰剂。患者接受了3周的治疗。在治疗期的开始和结束时测量尿动力学值。不良事件记录在患者的日记卡上。验证性的适应性程序和一个计划中的中期分析用于评估疗效。
结果：氯化ros的最大膀胱容量（中位治疗效果为22.0 mL，平均37.3 mL，单侧P = 0. 0054）和首次不稳定收缩时的尿量（中位治疗效果为45.0 mL，平均为63.6 mL）产生了显着改善。一侧P = 0.0015）。患者对疗效的评估显示，TC1组的临床改善明显高于安慰剂组（双面P = 0.0047）。此外，TC1的耐受性良好，两组中不良事件的发生频率相似（TCI中为68％，安慰剂组为62％）。
结论：氯化ros（20 mg，每天两次）是治疗逼尿肌不稳定的有效且安全的选择。

BACKGROUND & AIMS: :Expansion of trinucleotide repeats is associated with a growing number of human diseases. The mechanism and timing of expansion of the repeat tract are poorly understood. In humans, trinucleotide repeats show extreme meiotic instability, and expansion of the repeat tract has been suggested to occur in the germ-line mitotic divisions or postmeiotically during early divisions of the embryo. Studies in model organisms have indicated that polymerase slippage plays a major role in the repeat tract instability and meiotic instability is severalfold higher than the mitotic instability. We show here that meiotic instability of the CAG/CTG repeat tract in yeast is associated with double-strand break (DSB) formation within the repeated sequences, and that the DSB formation is dependent on the meiotic recombination machinery. The DSB repair results in both expansions and contractions of the CAG repeat tract.

背景与目标： 三核苷酸重复序列的扩增与越来越多的人类疾病有关。重复管道扩展的机理和时机知之甚少。在人类中，三核苷酸重复序列显示出极度的减数分裂不稳定，并且已暗示在胚系有丝分裂分裂中或在胚胎的早期分裂发生于减数分裂后，重复序列的扩增会发生。在模型生物中的研究表明，聚合酶滑移在重复道不稳定性中起主要作用，减数分裂不稳定性比有丝分裂不稳定性高出几倍。我们在这里显示，CAG / CTG重复序列在酵母中的减数分裂不稳定与重复序列内的双链断裂（DSB）形成有关，并且DSB的形成取决于减数分裂重组机制。 DSB修复导致CAG重复道的扩张和收缩。

BACKGROUND & AIMS: BACKGROUND:There is an increasing body of evidence that human pluripotent stem cells (hPSCs) are prone to (epi)genetic instability during in vitro culture. This review aims at giving a comprehensive overview of the current knowledge on culture-induced (epi)genetic alterations in hPSCs and their phenotypic consequences. METHODS:Combinations of the following key words were applied as search criteria: human induced pluripotent stem cells and human embryonic stem cells in combination with malignancy, tumorigenicity, X inactivation, mitochondrial mutations, genomic integrity, chromosomal abnormalities, culture adaptation, aneuploidy and CD30. Only studies in English, on hPSCs and focused on (epi)genomic integrity were included. Further manuscripts were added from cross-references. RESULTS:Numerous (epi)genetic aberrations have been detected in hPSCs. Recurrent genetic alterations give a selective advantage in culture to the altered cells leading to overgrowth of abnormal, culture-adapted cells. The functional effects of these alterations are not yet fully understood, but suggest a (pre)malignant transformation of abnormal cells with decreased differentiation and increased proliferative capacity. CONCLUSIONS:Given the high degree of (epi)genetic alterations reported in the literature and altered phenotypic characteristics of the abnormal cells, controlling for the (epi)genetic integrity of hPSCs before any clinical application is an absolute necessity.

背景与目标： 背景：越来越多的证据表明，人多能干细胞（hPSC）在体外培养过程中容易发生（表观）基因不稳定性。这篇综述旨在对hPSCs中由文化引起的（epi）遗传改变及其表型后果的当前知识进行全面概述。
方法：以下关键词组合作为搜索标准：人诱导的多能干细胞和人胚胎干细胞与恶性肿瘤，致瘤性，X失活，线粒体突变，基因组完整性，染色体异常，培养适应性，非整倍性和CD30结合在一起。只包括了英文的关于hPSC的研究，这些研究集中在（epi）基因组完整性上。从交叉引用中添加了更多手稿。
结果：在hPSC中检测到大量（epi）遗传畸变。反复发生的遗传改变在培养中赋予了改变的细胞以选择性的优势，从而导致异常的，适应培养的细胞过度生长。这些改变的功能作用尚不完全清楚，但表明异常细胞的（恶性）转化具有减少的分化和增加的增殖能力。
结论：鉴于文献中报道的高度（epi）遗传改变和异常细胞的表型特征改变，在任何临床应用之前控制hPSC的（epi）遗传完整性是绝对必要的。

BACKGROUND & AIMS: :Oxidative DNA damage is likely to be involved in the etiology of cancer and is thought to accelerate tumorigenesis via increased mutation rates. However, the majority of malignant cells acquire a specific type of genomic instability characterized by large-scale genomic rearrangements, referred to as chromosomal instability (CIN). The molecular mechanisms underlying CIN are not entirely understood. We utilized Saccharomyces cerevisiae as a model system to delineate the relationship between genotoxic stress and CIN. It was found that elevated levels of chronic, unrepaired oxidative DNA damage caused chromosomal aberrations at remarkably high frequencies under both selective and nonselective growth conditions. In this system, exceeding the cellular capacity to appropriately manage oxidative DNA damage resulted in a "gain-of-CIN" phenotype and led to profound karyotypic instability. These results illustrate a novel mechanism for genome destabilization that is likely to be relevant to human carcinogenesis.

背景与目标： ：氧化性DNA损伤可能与癌症的病因有关，并被认为可通过增加突变率来加速肿瘤发生。然而，大多数恶性细胞获得了以大规模基因组重排为特征的特定类型的基因组不稳定性，称为染色体不稳定性（CIN）。尚未完全了解CIN的分子机制。我们利用酿酒酵母（Saccharomyces cerevisiae）作为模型系统来描述遗传毒性应激与CIN之间的关系。已经发现，在选择性和非选择性生长条件下，慢性，未修复的氧化性DNA损伤的升高水平导致染色体畸变的频率很高。在该系统中，超过细胞容量以适当地控制氧化性DNA损伤会导致“ CIN获得”表型，并导致严重的核型不稳定性。这些结果说明了基因组不稳定的新机制，可能与人类致癌作用有关。

BACKGROUND & AIMS: :The role of developmental instability (DI), as measured by fluctuating asymmetry (FA), in evolutionary biology has been the focus of a wealth of research for more than half a century. In spite of this long period and many published papers, our current state of knowledge reviewed here only allows us to conclude that patterns are heterogeneous and that very little is known about the underlying causes of this heterogeneity. In addition, the statistical properties of FA as a measure of DI are only poorly grasped because of a general lack of understanding of the underlying mechanisms that drive DI. If we want to avoid that this area of research becomes abandoned, more efforts should be made to understand the observed heterogeneity, and attempts should be made to develop a unifying statistical protocol. More specifically, and perhaps most importantly, it is argued here that more attention should be paid to the usefulness of FA as a measure of DI since many factors might blur this relationship. Furthermore, the genetic architecture, associations with fitness and the importance of compensatory growth should be investigated under a variety of stress situations. In addition, more focus should be directed to the underlying mechanisms of DI as well as how these processes map to the observable phenotype. These insights could yield more efficient statistical models and a unified approach to the analysis of patterns in FA and DI. The study of both DI and canalization is indispensable to obtain better insights in their possible common origin, especially because both have been suggested to play a role in both micro- and macro-evolutionary processes.

背景与目标： 过去半个多世纪以来，通过波动不对称性（FA）衡量的发育不稳定性（DI）在进化生物学中的作用一直是众多研究的重点。尽管有这么长的时间和许多已发表的论文，但这里回顾的当前知识状态仅使我们得出结论，即模式是异质的，对这种异质性的根本原因知之甚少。此外，由于一般缺乏对驱动DI的潜在机制的了解，因此FA对作为DI的度量的统计属性的了解很少。如果我们要避免这一研究领域被放弃，则应做出更多的努力来理解观察到的异质性，并应尝试开发统一的统计协议。更具体地讲，也许是最重要的是，这里争论的是，应该更多地注意FA作为DI量度的效用，因为许多因素可能使这种关系变得模糊。此外，应在各种压力情况下研究遗传结构，与适应性的关系以及代偿性生长的重要性。此外，应更加关注DI的潜在机制以及这些过程如何映射到可观察的表型。这些见解可以产生更有效的统计模型，以及用于分析FA和DI模式的统一方法。对DI和渠化的研究对于获得它们可能的共同起源的更好的见解是必不可少的，特别是因为已建议两者都在微观和宏观进化过程中发挥作用。

BACKGROUND & AIMS: :A panel of five quasimonomorphic mononucleotide repeats that dispenses with the need to analyse corresponding germline DNA was proposed by Suraweera et al for the detection of high-frequency microsatellite instability (MSI) in colorectal cancer. Using this panel, a simplified and a more sensitive (compared with the original) algorithm (p<0.05) was developed to define the instability of each repeat by assessing the morphological shape of its plot and not its absolute length. 103 cases of colorectal tumours were investigated and the results compared with those obtained by the analysis of five consensus microsatellites (Bethesda reference panel). By the proposed method, a higher specificity, but no loss of sensitivity, was found. Thus, the use of the five mononucleotide repeats in combination with the modified assessment technique simplifies the assessment of MSI, while retaining the sensitivity of the Bethesda panel for the detection of high-frequency MSI.

背景与目标： Suraweera等人提出了一组五种准单态单核苷酸重复序列，这些重复序列无需分析相应的种系DNA，可用于检测大肠癌中的高频微卫星不稳定性（MSI）。使用该面板，开发了一种简化且更灵敏（与原始算法相比）的算法（p <0.05），通过评估图的形态学形状而非绝对长度来定义每个重复的不稳定性。研究了103例大肠肿瘤，并将结果与​​通过分析五个共有微卫星（贝塞斯达参考文献）获得的结果进行了比较。通过提出的方法，发现了更高的特异性，但没有灵敏度的损失。因此，将五个单核苷酸重复序列与改进的评估技术结合使用可简化对MSI的评估，同时保留Bethesda面板对检测高频MSI的敏感性。

BACKGROUND & AIMS: PURPOSE:The purpose of our study was to investigate the performance of MRI findings to predict instability of osteochondral lesion of the talus (OLT) in children and the association between skeletal maturity and lesion stability. MATERIALS AND METHOD:This retrospective IRB-approved and HIPPA-compliant study included children with OLT, who underwent an ankle MRI examination between March 1, 2011, and May 31, 2018. Blinded to the clinical outcome, 2 radiologists retrospectively assessed each MRI study for the presence or absence of various features on the articular side, along the interface, and on the subchondral side of each lesion. Regional skeletal maturity was recorded. Lesion stability was classified using clinical and surgical findings. Mann-Whitney U, Chi-square, Fisher's exact, and Cochran-Armitage tests were used to compare demographic and MRI findings between children with stable and unstable lesions. RESULTS:Of the 48 ankles identified, 36 were stable (12.7 + 3.9 years) and 12 were unstable (14.2 + 1.6 years) lesions. None of the lesions presented as a detached fragment. Skeletal immaturity (p = 0.01) was significantly more common in stable than unstable lesions. No other MRI features were found to be significantly different between stable and unstable lesions, which included the presence of an effusion (p = 0.27), intra-articular body (p = 0.25), cartilage changes (p = 0.19), subchondral disruption (p = 0.51), T2-weighted signal intensity rim (p = 0.16), cysts (p = 0.48), marginal sclerosis (p = 0.70), and perilesional marrow edema (p = 0.17). CONCLUSION:Results from our study suggest that previously published OCD criteria using conventional MRI are not sufficient for predicting stability of OLT in children. Regional skeletal maturity and older age were more predictive of unstable lesions.

背景与目标： 目的：我们的研究目的是调查MRI表现的性能，以预测儿童距骨骨软骨损伤（OLT）的不稳定性以及骨骼成熟度和病变稳定性之间的关系。
材料与方法：这项回顾性IRB批准且符合HIPPA的研究纳入了OLT儿童，他们在2011年3月1日至2018年5月31日期间接受了踝部MRI检查。对临床结果无知，两名放射科医生对每项MRI研究进行了回顾性评估。在每个病变的关节侧，沿界面以及软骨下侧是否存在各种特征。记录区域骨骼成熟度。使用临床和手术结果对病变稳定性进行分类。 Mann-Whitney U，卡方检验，Fisher's精确检验和Cochran-Armitage检验用于比较病灶稳定和不稳定的儿童的人口统计学和MRI表现。
结果：在确定的48条脚踝中，有36处稳定（12.7年3.9年），有12处不稳定（14.2年1.6年）的病变。没有一个病灶表现为分离的碎片。稳定状态的骨骼不成熟率（p = 0.01）比不稳定状态的患病率高得多。没有发现稳定和不稳定病变之间的其他MRI特征有显着差异，包括存在积液（p = 0.27），关节内体（p = 0.25），软骨变化（p = 0.19），软骨下破坏（ p = 0.51），T2加权信号强度边缘（p = 0.16），囊肿（p = 0.48），边缘性硬化症（p = 0.70）和病灶周围骨髓水肿（p = 0.17）。
结论：我们的研究结果表明，以前发表的使用常规MRI的OCD标准不足以预测儿童OLT的稳定性。区域骨骼的成熟度和年龄更大地预测不稳定的病变。