生物陶瓷系统微创治疗 ARCO Ⅱ、Ⅲ期股骨头坏死

目的完善 β 磷酸三钙（β tricalcium phosphate，β-TCP）生物陶瓷系统微创治疗股骨头坏死（osteonecrosis of the femoral head，ONFH）的理论体系，评估其临床疗效。方法取 7～8 月龄雄性新西兰大白兔 18 只制备血管化动物模型，术后 4、8、12 周采用 micro-CT 扫描血管三维重建和荧光背景下血管显像观察新生血管形态，并计算血管长入包裹区的深度、血管数目以及血管直径。取 9 个猪股骨标本随机分为 3 组（n=3）：A 组为正常股骨头颈组；B 组为空腔组（隧芯减压通道+股骨头内球形骨缺损）；C 组为植骨组，打压植入混合陶瓷颗粒填充股骨头内球形缺损，骨隧道内植入 β-TCP 多孔生物陶瓷棒。行生物力学检测计算标本的刚度及屈服载荷。多中心回顾分析 2012 年 1 月—2018 年 7 月，国内 7 所医疗中心行生物陶瓷系统微创保髋治疗的 ONFH 患者 200 例（232 髋）。其中男 145 例，女 55 例；年龄 17～76 岁，平均 42 岁。按照国际骨循环协会（ARCO）分期为Ⅱ期 150 髋，Ⅲ期 82 髋。术后定期对患者进行影像学评估，采用 Harris 评分对髋关节功能进行评价，并比较 ARCO Ⅱ期与Ⅲ期患者的临床疗效。 结果动物实验结果显示血管可由多孔生物陶瓷棒非包裹区长入包裹区，至 12 周时可见血管贯穿包裹区。随术后时间延长，血管长入包裹区的深度、血管数目、血管直径均逐渐增加，各时间点间比较差异均有统计学意义（P<0.05）。生物力学检测示，B、C 组标本刚度和屈服载荷显著低于 A 组，B 组屈服载荷显著低于 C 组，差异均有统计学意义（P<0.05）；C 组股骨头颈的刚度恢复至 A 组的 41.52%±3.96%，屈服载荷恢复至 A 组的 46.14%±7.85%。临床研究显示，200 例患者均获随访，随访时间 6～73 个月，平均 22.7 个月。至末次随访时有 12 例（16 髋）行全髋关节置换术，髋关节生存率为 93.10%；根据影像学评估，184 髋（79.31%）影像学稳定，48 髋（20.69%）出现影像学进展；Harris 评分为（79.3±17.3）分，较术前（57.3±12.0）分显著改善（t=18.600，P=0.000）；优良率达 64.22%（149/232）。ARCO Ⅱ期患者在髋关节生存率、影像学评估、Harris 评分方面均优于 ARCO Ⅲ期患者（P<0.05）。 结论β-TCP 生物陶瓷系统微创治疗 ONFH，可引导大转子及股骨颈血运至股骨头内促进坏死修复；术后早期可以部分恢复股骨头颈力学性能；该方法为 ONFH 患者，尤其是早期患者提供了一种新的保髋治疗选择。     

固有免疫系统在骨关节炎发病机制中的作用及研究进展

目的综述固有免疫系统在骨关节炎（osteoarthritis，OA）发病机制中的作用及研究进展。方法查阅国内外相关文献，对固有免疫系统介导的炎症及巨噬细胞、T 细胞、补体系统在 OA 发病机制中的作用、潜在治疗靶点及研究进展进行总结。结果随着研究深入，OA 逐渐被认为是一种低度炎症状态，固有免疫系统在其发生发展过程中发挥了重要作用。目前研究主要集中于 OA 滑膜组织巨噬细胞亚群极化方面，结果显示 M1 亚群向 M2 亚群转换失败是 OA 进展的关键环节。而 T 细胞及补体系统也参与了 OA 的病理过程。结论目前有关固有免疫系统对 OA 进展作用的研究仍处于探索阶段，具体机制尚未明确。现有研究结果提示，巨噬细胞亚群极化是早期防治 OA 的潜在靶点。     

Automatizing a nonscripting TPS for optimizing clinical workflow and reoptimizing IMRT/VMAT plans

The purpose of this study was to design a toolkit that interacts with the Monaco (Elekta AB, Stockholm, Sweden) treatment planning system (TPS) for optimization of intensity-modulated radiation therapy and volumetric-modulated arc therapy without the need for a dedicated application programming interface. Successful inverse planning of radiotherapeutic treatment depends on the tweaking of many parameters; a tool was thus needed to explore these parameters more exhaustively without significantly increasing planning time. The software that we used was based on an open-source library that mimics human interaction with Microsoft Windows applications. We developed a simple Autoflow software routine that analyzes and optimizes calculated plans by considering the relative impact of different cost functions and modifying constraints accordingly. It was also designed to change segmentation parameters to fit more complex treatments. The toolkit is publicly available for download at https://bitbucket.org/hgugmradiofisica/pymonaco/src/master/. A study of prostate cancer cases was conducted to compare automatically created plans with previously treated cases. The toolkit fully automated the radiotherapy planning procedure, allowing the TPS to calculate or optimize plans during nonworking hours. In the prostate study, the use of this tool reduced the dose to organs at risk with a negligible decrease in target coverage. This tool enables the efficient use of the TPS, allowing research and clinical applications to coexist without conflict. It provides consistency and efficiency throughout the treatment planning process, which may be of great value to clinics with few resources. The impact of this tool on clinical workflow is important, as it not only provides better efficiency, but also increases treatment quality.     

Evaluation of the PROMIS pediatric global health scale (PGH-7) in children with asthma

Objective: To evaluate the reliability and validity of the PROMIS Pediatric Global Health scale, a 7-item measure of perceived physical, mental, and social health, in children with asthma. Methods: From February 2014 to February 2015, convenience samples of 8–17 year-old children (n = 182) and parents of 5–17 year-old children (n = 328) visiting an emergency department for treatment of asthma were enrolled. The Asthma Control Test was used to characterize children as controlled versus not controlled, and the PROMIS Asthma Impact Scale was used to assess asthma symptoms' impact on functional status. We conducted longitudinal analyses among 92 children and 218 parents at 3 weeks, and 74 children and 171 parents at 8 weeks after enrollment. Results: The PGH-7 reliability ranged from 0.66 to 0.81 for child-report and 0.76 to 0.82 for parent-proxy. In cross-sectional analyses, children with controlled asthma had PGH-7 scores 0.40–0.95 standard deviation units higher than those who were uncontrolled. The PGH-7 was responsive to changes in overall general health between time points, with moderate effect sizes (0.5–0.6 standard deviation units). In longitudinal analyses, PGH-7 scores were no different between those who stayed uncontrolled versus became controlled at 3 weeks of follow-up; however, by 8 weeks of follow-up, the differences between these groups were 0.7–0.8 standard deviation units, indicative of large effects. Conclusions: The PGH-7 is a reliable and valid patient-reported outcome for assessing general health among children with asthma. It is a useful complement to other asthma-specific outcome measures.     

Rates of reoperation and nonoperative intervention within 30 days of bariatric surgery

BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ² for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG.     

膝关节前外侧韧带的研究进展

目的对膝关节前外侧韧带（anterolateral ligament，ALL）的研究进展进行综述，为临床诊治提供参考。方法广泛查阅近年来国内外有关 ALL 损伤诊断及治疗的文献，总结膝关节 ALL 解剖形态、生物力学以及 ALL 损伤机制、治疗现状。结果膝关节 ALL 具有限制胫骨内旋及前移作用，影响膝关节轴移。ALL 损伤后可结合患者体征和 MRI 检查诊断。膝关节 ALL 手术指征尚未统一，但多数学者倾向于对需进行前交叉韧带（anterior cruciate ligament，ACL）重建或翻修且伴有高度轴移试验阳性的患者进行 ALL 重建。目前 ALL 重建方式较多，但尚无最佳治疗术式。此外，由于缺乏高质量的术后长期随访研究，远期临床疗效仍不明确。结论ALL 在维持膝关节稳定性方面具有一定作用，但 ALL 重建技术及临床疗效仍待进一步研究。     

Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells

Objective: This study aimed to explore Hesperetin (Hst) potency as a co-chemotherapeutics agent combined with Doxorubicin (Dox), particularly cytotoxic and antimetastasis effects toward MCF-7/HER2 cells. Methods: The cytotoxic effects were measured under MTT assay. The flowcytometry analysis was used to examine the cell cycle modulation and apoptosis evidence, while the effect of migration was assayed by scratch wound healing assay. Western blotting and gelatin zymography were carried out to examine the expression level of proteins, HER2, and Rac1. Results: Under MTT assay, Hst and Dox exhibited to decrease cell viability in a dose-dependent manner with the IC50 value of 377 and 0,8 µM, respectively. The combination of Hst and Dox at the respective doses of 95 and 0,2 µM showed a synergistic effect with the combination index of 0,63. Flow cytometry analysis of Hst-Dox revealed that those compounds caused cell cycle arrest at the G2/M phase and induced apoptosis. Hst also decreased HER2 and Rac1 expression, as shown by western blot. Hst inhibited lamellipodia formation and cell migration, as indicated by microscopic observation and wound healing scratch assay. The antimetastatic activity of Hst was associated with the reduction of Rac1 and MMP9 expression as measured by gelatine zymography assay. Conclusion: These results indicated that the combination of Hst and Dox-induced cell cycle arrest, apoptosis, decreased HER2, Rac1, MMP9 expression, and cell migration. Thus, Hst may have the potential to be developed as a co-chemotherapeutic agent combined with doxorubicin toward HER2 overexpressing breast cancer cells.