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91.
背景与目的以免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而,对于程序性死亡受体配体1(programmed cell death-ligand 1, PD-L1)高表达,即肿瘤比例评分(tumor proportion score, TPS)≥50%的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者,采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色,按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率(objective response rate,ORR)和无进展生存时间(progression free survival, PFS)。结果免疫单药与免疫联合化疗组的ORR分别为47.1%(8/17)和43.8%(14/32),差异无统计学意义(P=0.825)。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月,差异无统计学意义(P=0.502)。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析,结果显示,一线免疫治疗ORR(12/19, 63.2%)显著优于二线及以上免疫治疗(10/30, 33.3%),差异有统计学意义(P=0.041),二者间PFS无差异。年龄、性别、吸烟史、功能状态评分(performance status, PS)、病理类型、肿瘤大小、肿瘤淋巴结转移(tumor node metastasis, TNM)分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。 相似文献
92.
《Clinical neurophysiology》2021,132(12):3104-3115
ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials. 相似文献
93.
Rohi Shah Nomaan Sheikh Jitendra Mangwani Nicolette Morgan Hamidreza Khairandish 《Journal of Clinical Orthopaedics and Trauma》2021,12(1):138
Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC. 相似文献
94.
95.
ABSTRACTThis work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated. 相似文献
96.
A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures. 相似文献
97.
目的 通过观察早产儿不同胎龄Toll样受体9(TLR9)的表达,探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份,按胎龄分为4组,28~31周组,31~34周组,34~37周组,≥37周组,采用流式细胞术和实时荧光定量PCR方法,分别检测其TLR9的蛋白和mRNA表达情况,了解其与胎龄之间的关系,并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组,31~34周组,34~37周组,≥37周组分别为(15.93±6.23)%,(11.63±6.70)%,(13.66±6.88)%,(20.51±12.06)%;其在胎龄28~31周较高,至31~34周逐渐下降至最低,两组差异有统计学意义(P<0.05);34~37周后TLR9阳性细胞率表达逐渐升高,至≥37周达最高,两胎龄组比较,差异具有统计学意义(P<0.05)。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关(r=0.273,P=0.006)。TLR9 mRNA表达在28~31周组,31~34周组,34~37周组,≥37周组分别为(4.95±3.44)%,(8.89±8.49)%,(13.91±10.92)%,(7.19±7.11)%;其在28~36周逐渐升高,与胎龄呈正相关(r=0.355,P< 0.001)。≥37周TLR9 mRNA表达量下降,该值虽高于28~31周,但差异无统计学意义(P>0.05)。相关性分析表明,同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关(r=-0.227,P=0.011)。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异,TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加,TLR9 mRNA在28~36周间随着胎龄的增加而增加。 相似文献
98.
99.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
100.