A Warhead Substitution Study on the Coronavirus Main Protease Inhibitor Nirmatrelvir

The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections.     

液体衰减翻转恢复序列在颅脑MRI中的应用

目的：探讨１．５ＴＭＲ颅脑液体衰减翻转恢复（ＦＬＡＩＲ）序列的合理扫描参数及其临床应用价值。材料和方法：首先对１８名健康志愿者行１．５ＴＭＲ的颅脑ＦＬＡＩＲ序列的参数选择试验，然后用筛选出的合理参数对２４例脑部疾病患者行ＦＬＡＩＲ序列与ＳＥ序列的对照扫描。结果：在１．５ＴＭＲ颅脑ＦＬＡＩＲ扫描中，当ＴＲ＝６０００ｍｓ时，ＴＩ为１７００－１８００ｍｓ接近脑脊液的无效值，ＴＥ以１６０ｍｓ为宜。ＦＬＡＩＲ序列与ＳＥ序列的对照扫描中，ＦＬＡＩＲ序列显示病变为７５／７６（９８．６８％），ＳＥ序列为６５／７６（８５．５３％），两者显示病变的敏感度有显著性差异（Ｐ＜０．０１）。结论：ＦＬＡＩＲ序列对靠近脑脊液的病变、脑组织水肿、室管膜下漏液、脑室和脑池内病变的检出较ＳＥ序列更敏感。     

纤变灵对口腔粘膜下纤维化及血液流变学的影响

目的观察中药复方纤变灵治疗口腔粘膜下纤维化（OSF）的临床疗效及对血液流变学的影响。方法将确诊为OSF的66例患者随机分为两组,治疗组34例,对照组32例,分别给予纤变灵和维生素A、E口服,观察两种药物的临床疗效、血液流变学指标的变化。结果纤变灵治疗OSF临床疗效明显优于维生素A、E（p〈0.05）;全血粘度、血浆粘度、纤维蛋白原等血液流变学指标均有明显改善（p〈0．05或p〈0．01）。结论纤变灵治疗OSF安全有效,并能降低血液粘度、改善微循环。     

77例骨肉瘤患者预后的多因素分析

目的：探讨影响骨肉瘤患者预后的相关因素。方法：回顾性分析2000年1月至2011年10月,77例资料完整骨肉瘤患者的临床资料,并根据是否接收化疗药物治疗且坚持4个周期以上分为规律化疗组及非规律化疗组。结果：规律化疗组患者的比例为54.55％（42／77）,非规律化疗组的比例为45.45％（35／77）。所有患者生存时间为9—62个月,5年总体生存率为44.16％（34／77）,平均生存时间3671±1480个月,中位生存时间为31个月。规律化疗组患者5年生存率（50.00％,21／42）显著高于非规律化疗组（37.14％,13／35）（Log Rank：χ^2=8.27,P=0.004）;COX多因素分析发现：Enneking分期、手术方式及规律化疗是影响骨肉瘤患者5年生存率的独立因素。结论：Enneking分期、手术方式及规律化疗是影响骨肉瘤患者预后的独立因素。     

Effect of humeral head rotation on bony glenohumeral stability

BackgroundThe humeral head and glenoid cavity are not perfectly spherical, nor do they have matching radii of curvature. We hypothesized that glenohumeral stability is dependent on axial humeral rotation.MethodsSeven cadaveric shoulders were investigated. For each test, the humeral head was translated relative to the glenoid in 2 directions (starting from neutral), anterior and anteroinferior. Contact forces and lateral humeral displacement were recorded. Joint stability was quantified using the stability ratio and energy to dislocation. The humerus was set in 60° of abduction for all tests. Testing was performed in neutral rotation and 60° of external rotation.FindingsThe force displacement curves differed between rotations. In both displacement directions, the peak translational force occurred with less displacement in neutral rotation than in external rotation. The stability ratio and energy to dislocation in the anteroinferior direction were greater than in the anterior direction for both rotation positions. While there were no significant differences in the stability ratio or energy to dislocation between rotation conditions at complete dislocation, the energy required to move the humeral head 10% of the glenoid width was significantly greater with the arm in neutral rotation.InterpretationThe energy to dislocation, a new parameter of dislocation risk, and the stability ratio, indicate that the glenohumeral joint is more stable in the anteroinferior direction than the anterior direction. During initial displacement, axial rotation of the humeral head contributes to glenohumeral geometrical stability. However, humeral head rotation does not have a significant effect when looking at complete dislocation.     

Dynamic joint forces during knee isokinetic exercise

This study analyzed forces in the tibiofemoral and patellofemoral joints during isokinetic exercise using an analytical biomechanical model. The results show that isokinetic exercise can produce large loads on these joints, especially during extension exercises. The tibiofemoral compressive force (4.0 body weight) is approximately equal to that obtained during walking but it occurs at 55 degrees of knee flexion. Anterior shear forces (resisting force to anterior drawer) exist during extension exercise at less than 40 degrees of knee flexion, with a maximum of 0.3 body weight. Posterior shear forces (resisting force to posterior drawer) exist during extension exercise at knee joint angles greater than 40 degrees and during the flexion portion of isokinetic exercise. The maximum posterior shear force is 1.7 body weight. The patellofemoral joint can encounter loads as high as 5.1 body weight which are 10 times higher than during straight leg raises. These results suggest that isokinetic exercise should be used cautiously in patients with knee lesions.