Risk-based,response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.     

PD-1/PD-L1免疫检查点抑制剂在多形性胶质母细胞瘤中的研究进展

多形性胶质母细胞瘤(Glioblastoma multiforme, GBM)是目前最常见的原发性恶性脑肿瘤之一。GBM具有高侵袭性、高复发率和低生存率等特点,预后较差。程序性细胞死亡受体1(Programmed cell death receptor 1,PD-1)/程序性细胞死亡配体1(Programmed cell death ligand 1,PD-L1)作为主要的免疫检查点(Immune checkpoint, IC),形成免疫通路,可触发免疫反应的负性调控,增强脑组织中GBM细胞的侵袭性。在GBM的治疗研究中,免疫检查点抑制剂(Immune checkpoint inhibitor, ICI)也受到了相当大的关注。ICI通过抑制负性免疫调节途径来激活抗肿瘤反应,为GBM提供了新的治疗途径。目前已有多项临床研究集中在标准治疗(替莫唑胺、放疗)、靶向治疗和其他免疫治疗的联合应用方面。本综述阐述了PD-1/PD-L1通路,概述了PD-1/PD-L1 ICI单药、新辅助治疗以及联合化疗、放疗、靶向治疗、激素等多种方式治疗GBM的研究进展。     

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA

ObjectivesThe inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).Materials and MethodsPRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.ResultsIn healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.ConclusionsWe showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.     

Stable mechanical environments created by a low-tension traction device is beneficial for the regeneration and repair of degenerated intervertebral discs

BACKGROUNDBy blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful.PURPOSEIn the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration.STUDY DESIGNA macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction.METHODSSix-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7−Co10], while Co8−Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8−Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate.RESULTSAfter 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8–Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D–G). In addition, histologic scores of the intervention groups (D–G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D–G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF.CONCLUSIONSDegenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction.     

单侧双通道内镜技术治疗腰椎间盘突出症的疗效及去骨量分析

目的:比较单侧双通道内镜(unilateral biportal endoscopic,UBE)和椎板小开窗术式治疗腰椎间盘突出症(lumbar disc herniation,LDH)的临床疗效及骨去除量。方法:回顾性分析2019年12月至2021年12月收治的105例单节段LDH患者,其中54例接受UBE治疗(UBE组),男32例,女22例,年龄18～50 (38.7±9.3)岁:L_4-529例,L₅S₁25例。51例接受椎板小开窗术式治疗(椎板小开窗组),男27例,女24例,年龄18～50(39.9±10.0)岁;L_4,525例,L₅S₁26例。观察并比较两组手术时间、术后下床时间、住院时间等围手术期指标,分别于术前和术后1、3、6、12个月比较两组腰腿痛视觉模拟评分(visual analogue scale,VAS)、Oswestry功能障碍指数(Oswestry disability index,ODI),并采用改良MacNab标准进行临床疗效...     

糖尿病对关节镜下肩袖修复术后病人肩关节功能恢复影响的临床研究

目的 探讨糖尿病对关节镜下肩袖修复术后病人肩关节功能恢复的影响。方法 回顾性分析我科自2019年5月至2022年5月接受关节镜下肩袖修复术的62例肩袖损伤病人的临床资料和随访结果,其中糖尿病组30例,男18例,女12例,年龄为（62.10±11.87）岁;对照组32例,男18例,女14例,年龄为（63.78±12.98）岁。手术方式均为关节镜下缝线桥技术缝合肩袖。分别记录两组病人术前1周、术后3个月、6个月和12个月各时间点肩关节最大外展角度值,以及肩关节功能评分,包括疼痛视觉模拟量表（visual analogue scale,VAS）评分、美国肩肘外科协会（American Shoulder Elbow Surgeon,ASES）评分、加州大学洛杉矶分校（University of California at Los Angeles,UCLA）肩关节评分以及Constant-Murley评分。据此对手术效果进行评估。结果 62例病人均未出现伤口感染、术后僵硬、术后再撕裂等并发症。两组病人的肩关节最大外展角度值、VAS评分、ASES评分、UCLA评分以及Constant-Murley...