Forward and Reverse Middle Ear Transmission in Gerbil with a Normal or Spontaneously Healed Tympanic Membrane

Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear.     

锁骨钩钢板内固定术后钢板钩与肩峰匹配性影像学研究

目的通过测量锁骨钩钢板内固定术后患者影像学资料，分析发生肩峰骨侵蚀的原因是否与钢板钩-肩峰匹配度相关。 方法回顾性分析2015年8月1日至2018年8月31日期间在上海市浦东医院骨科就诊的210例患者的影像学资料，210例患者均因肩锁关节脱位或锁骨远端骨折行锁骨钩钢板内固定治疗，其中男110例、女100例；年龄24~76岁，平均（44.60±8.75）岁；肩锁关节脱位70例，锁骨远端骨折140例。测量术后及终末随访患者肩锁关节正位X线片相关数据，按锁骨钩钢板术后是否发生肩峰骨侵蚀，将纳入患者分为3组：无骨侵蚀组（A组）、伴钢板钩移位骨侵蚀组（B组）、不伴移位的骨侵蚀组（C组），分别测量钢板钩-肩峰的匹配度（β），统计分析术后发生肩峰骨侵蚀与钢板钩-肩峰匹配度之间的关系。 结果纳入研究的210例患者术后随访24~64周，平均（32.0±6.5）周。A组患者115例，B组患者54例，C组患者41例。A组匹配度β（3.72±0.48）mm与B组β¹（6.91±0.84）mm比较差异有统计学意义（P<0.05）；A组匹配度β（3.72±0.48）mm与C组β²（5.88±0.65）mm比较差异有统计学意义（P<0.05）；B组匹配度β¹（6.91±0.84）mm与C组β²（5.88±0.65）mm比较差异有统计学意义（P<0.05）。 结论锁骨钩钢板内固定术后是否发生肩峰骨侵蚀与钢板钩-肩峰匹配度β存在明显相关性，钢板钩与肩峰之间的匹配度越好，β值越小，发生肩峰骨侵蚀的可能性更小。     

IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4

Investigational New Drugs - Background&nbsp;Chemotherapy resistance is a main reason for treatment failure in extranodal NK/T-cell lymphoma (ENKTL). Interleukin-10 (IL-10) is closely related to...     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.