Unique genomic profiles obtained from cerebrospinal fluid cell-free DNA of non-small cell lung cancer patients with leptomeningeal metastases

Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled.

Methods: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy.

Results: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001).

Conclusions: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.     

中医治疗肾阳虚模型研究进展

通过回顾近年来中医治疗肾阳虚模型的相关文献，主要从中药治疗、针灸疗法及其作用机制探讨肾阳虚证的本质。中药治疗肾阳虚模型的作用机制有调节免疫系统、调节能量代谢、调节下丘脑-垂体-靶腺轴及调节整体生长性能等，而针灸疗法作用机制有调节垂体-性腺轴、垂体肾上腺轴及垂体-甲状腺轴等。中医治法被广泛应用于肾阳虚证的治疗，对疾病的诊治及预防均有一定优势。     

不同剂量A型肉毒毒素肌注对脑卒中后肌痉挛患者肌力和步行功能的影响

目的探讨不同剂量A型肉毒毒素肌注对脑卒中后肌痉挛患者肌力和步行功能的影响。方法前瞻性选取延安大学咸阳医院2015年8月至2017年8月收治的96例卒中后恢复期患者,按随机数表法分为大剂量组、中剂量组与小剂量组,各32例。三组均在常规康复训练基础上联合A型肉毒毒素肌注治疗其中大剂量组注射剂量400 U,中剂量组300 U/,小剂量组200 U,浓度均为50 U/ml。比较三组A型肉毒毒素起效时间与持续时间,治疗前与治疗后3个月的肌力恢复情况(采用改良A shworth分级评分评价)、步行功能(采用Holden步行功能评估)、10 m步行时间与日常生活能力(应用改良Barthel指数评估)、临床神经功能缺损程度(采用NDS评分)及不良反应总发生率。结果大剂量组起效时间明显较中剂量组与小剂量组更快,持续时间较中剂量组与小剂量组更长(P<0.05)。三组治疗前的Ashworth评分、Holden评分、10 m步行时间与BI指数的差异无统计学意义(P>0.05);治疗后3个月三组Ashworth评分与10 m步行时间均较治疗前显著减小、Holden评分与BI指数较治疗前显著增大(P<0.05)。大剂量组治疗后3个月的Ashworth评分与10 m步行时间显著低于中剂量组与小剂量组、Holden评分与BI指数显著高于中剂量组与小剂量组(P<0.05)。治疗后3个月三组NDS评分均较治疗前显著减小(P<0.05)。大剂量组治疗后3个月的NDS评分显著低于中剂量组与小剂量组(P<0.05)。大剂量组与中剂量组不良反应总发生率9.38%与3.13%,差异无统计学意义(P>0.05)。结论A型肉毒毒素可促进卒中后肌痉挛患者肌力与步行功能的恢复,提高日常生活能力,且大剂量组应用的起效时间最快、持续时间最长,效果最优,同时不良反应未见明显增加,为最佳应用剂量。     

中药糖肾方单体成分莫诺苷药理作用的研究进展

通过查阅近些年的国内外文献对中药糖肾方单体成分莫诺苷的药理作用及分子机制进行归纳、梳理、分析及总结。从分子机制角度阐述莫诺苷具有促进细胞生长、减轻炎性反应、抑制细胞内钙超载、抑制氧化应激、抗凋亡、抗凝等作用,以便为今后临床及实验研究提供更多科学依据。     

复发性肝癌再次手术方式的选择:一项基于倾向评分匹配的研究

目的本研究基于倾向评分匹配(PSM)比较挽救性肝移植(sLT)及再次肝切除(RR)的疗效,同时探讨影响复发性肝癌患者预后的危险因素。方法回顾分析2012年1月至2018年8月宁波大学附属李惠利医院124例肝癌切除术后肝内复发再手术的患者,按照再次所行手术方式的不同,分成sLT组(46例)和RR组(78例),通过1∶1倾向评分匹配(PSM),筛选出34例患者用于数据分析,比较匹配前后两组的临床基本资料、总生存期(OS)及无瘤生存期(DFS)来探讨两种手术方式的优劣以及影响患者预后的因素。结果匹配前sLT组的术前血清总胆红素、多发肿瘤的比例、术前行经导管动脉化疗栓塞术(TACE)的比例及符合米兰标准的比例均要高于RR组(P<0.05),最大肿瘤直径sLT组要小于RR组(P<0.05);手术时间、术中出血量、微血管侵犯(MVI)阳性率及术后ClavienⅢ级以上的并发症的比例均要高于RR组(P<0.05)。匹配后sLT组的手术时间、术中出血量、术后并发症ClavienⅢ以上的比例均高于RR组(P<0.05);sLT组的1、3、5年OS与RR组相比差异无统计学意义(P>0.05),sLT组的1、3、5年DFS与RR组相比较优(P<0.05);甲胎蛋白(AFP)≥100μg/L是OS的独立危险因素,手术方式、AFP≥100μg/L是DFS的独立危险因素。结论sLT组术前病情更重,手术时间、术中出血量及术后严重并发症率高于RR组;sLT组较RR组可取得更长的DFS,但对OS来说,两组之间差异无统计学意义。     

A quasi-experimental evaluation of advance care planning improves consistency between elderly individuals and their surrogates regarding end-of-life care preferences: Development and application of a decision aid with cartoon pictures

ObjectiveThis study sought to develop a decision aid with cartoon pictures and evaluate its effectiveness in increasing consistency between elderly individuals and their surrogates regarding end-of-life care.MethodsA pre-post quasi-experimental design was adopted using the Life Support Preferences Questionnaire. The intervention had two components: (1) increasing participants’ knowledge of medical treatments related to end-of-life care, and (2) sharing their end-of-life wishes. The experimental group received an intervention, whereas the control group received usual care.ResultsA total of 110 participants in 55 pairs of elderly individuals with average aged 86.4 and their surrogates (27 in the experimental group, 28 in the control group) were recruited from a veterans hospital in northern Taiwan. Nearly 90 % of elderly individuals were male. The multiple linear regression showed that the inconsistent gap between elderly individuals and their surrogates in the experimental group decreased 12 points than the control group after controlling the covariances (B = ?12.116, p = 0.032).ConclusionThe intervention improved the consistency between elderly individuals and their surrogates regarding end-of-life care.Practice implicationsA decision aid with cartoon pictures may support the discussion of end-of-life care in older Asian populations.     

Comparison of total hip arthroplasty with minimally invasive SuperPath approach vs. conventional posterolateral approach in elderly patients: A one-year follow-up randomized controlled research

ObjectiveTo compare difference between SuperPath approach and conventional posterolateral approach in total hip arthroplasty (THA) in elderly patients.MethodsThe present prospective randomized controlled single blinded study enrolled a total of 96 elderly patients who received THA in our hospital during April 2015 to December 2018. All patients were randomly divided into the SuperPath group and the conventional group. General demographic characteristics and intraoperative data, as well as hospitalization time were recorded. Harris scores were used for measurement of hip function and visual analogue scale (VAS) was used for pain measurement. Serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and creatine phosphokinase (CK) were measured before and 24 h after surgery. Gait analysis was conducted by the method of footprints.ResultsThe mean surgical time was remarkably longer, the mean blood loss and incision length were significantly lower and the hospitalization time was also shorter in the SuperPath group compared with the conventional group. Both levels of CRP and CK were remarkably lower in the SuperPath group. At time points of 7 d and 1 mon after surgery, the VAS scores were significantly lower, and at 7 d, 1 mon and 3 mon the Harris scores were markedly higher in the SuperPath group compared with the conventional group. The step length and stride speed were significantly larger in the SuperPath group at 7 d and 1 mon after surgery than the conventional group. Joint dislocation was found in 2 cases of patients in the conventional group and no dislocation case was found in the SuperPath group. The angles of anteversion showed no significant difference, while the angles of abduction were significantly lower in the SuperPath group.ConclusionPatients with SuperPath approach had lower levels of CRP, ESR and CK, better hip function and less pain, as well as better gait condition than patients with conventional posterolateral approach in elderly patients.     

Central nervous system diseases related to pathological microglial phagocytosis

Microglia are important phagocytes of the central nervous system (CNS). They play an important role in protecting the CNS by clearing necrotic tissue and apoptotic cells in many CNS diseases. However, recent studies have found that microglia can phagocytose parts of neurons excessively, such as the neuronal cell body, synapse, or myelin sheaths, before or after the onset of CNS diseases, leading to aggravated injury and impaired tissue repair. Meanwhile, reduced phagocytosis of synapses and myelin results in abnormal circuit connections and inhibition of remyelination, respectively. Previous studies focused primarily on the positive effects of microglia phagocytosis, whereas only a few studies have focused on the negative effects. In this review, we use the term "pathological microglial phagocytosis" to refer to excessive or reduced phagocytosis by microglia that leads to structural or functional abnormalities in target cells and brain tissue. The classification of pathological microglial phagocytosis, the composition, and activation of related signaling pathways, as well as the process of pathological phagocytosis in various kinds of CNS diseases, are described in this review. We hypothesize that pathological microglial phagocytosis leads to aggravation of tissue damage and negative functional outcome. For example, excessive microglial phagocytosis of synapses can be observed in Alzheimer's disease and schizophrenia, leading to significant synapse loss and memory impairment. In Parkinson's disease, ischemic stroke, and traumatic brain injury, excessive microglial phagocytosis of neuronal cell bodies causes impaired gray matter recovery and sensory dysfunction. We therefore believe that more studies should focus on the mechanism of pathological microglial phagocytosis and activation to uncover potential targets of therapeutic intervention.     

Ultrasound-Based Carotid Plaque Characteristics Help Predict New Cerebral Ischemic Lesions after Endarterectomy

The aim of this study was to identify the ultrasound-based carotid plaque characteristics associated with new cerebral ischemic lesions after carotid endarterectomy (CEA). Between January 2013 and December 2018, carotid duplex ultrasound was performed in 1061 patients who underwent CEA. Brain magnetic resonance diffusion-weighted imaging (DWI) was performed pre-operatively and within 30 d after CEA. New cerebral ischemic lesions on DWI were observed in 169 patients. The cutoff value gray-scale median (GSM) used to distinguish DWI-positive from DWI-negative patients was 30.5, with an area under the receiver operating characteristic curve of 0.837. A larger proportion of multiple DWI lesions were observed in the GSM ≤30.5 group (59.5% vs. 41.5%, p = 0.030). Univariate and multivariate analyses identified GSM ≤30.5, ulcerated carotid plaques and pre-operative ischemic symptoms as predictors of post-operative cerebral DWI lesions. Our results indicate that ultrasound-based carotid plaque characteristics help predict new cerebral ischemic lesions after CEA.