心源性脑卒中患者血栓弹力图检测与抗凝因子蛋白S、蛋白C的相关性研究

目的:探讨心源性脑卒中(CES)患者血栓弹力图检测与抗凝因子蛋白S、蛋白C的相关性。方法:选取2018年9月~2020年6月入院治疗的CES患者86例纳入CES组,同时选取同期健康体检者40例纳入健康组。检测两组TEG及抗凝因子蛋白S、蛋白C水平,对不同神经功能损伤严重程度及不同预后患者上述参数进行比较,分析TEG与蛋白S、蛋白C的相关性。结果:与健康组相比,CES组R值、K值、蛋白S、蛋白C水平明显降低,α值、MA值明显增高(P<0.05);随着病情严重程度升高,患者R值、K值、蛋白S、蛋白C水平明显降低,α值、MA值明显升高(P<0.05)。预后良好组R值、K值、蛋白S、蛋白C水平明显高于预后不良组,α值、MA值明显低于预后不良组(P<0.05);CES患者蛋白S及蛋白C水平与R值、K值呈正相关,与MA值呈负相关(P<0.05)。结论:CES患者TEG部分参数与抗凝因子蛋白S、蛋白C存在相关性,临床可以两种指标相互补充,增强患者凝血功能功能监测效果。     

Method’s corner: Allergist’s guide to network meta-analysis

Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care.     

3D打印骨折模型在复杂骨盆骨折手术中的治疗方法及效果探讨

目的:探讨复杂骨盆骨折手术治疗中3D打印骨折模型的应用方法及效果。方法:选取医院收治的60例复杂骨盆骨折患者,按照随机数表法将其分为对照组和观察组,每组30例。对照组行传统CT指导下手术治疗,观察组行3D打印仿真骨盆模型体外模拟术后,应用腹直肌旁切口钢板内固定术治疗。比较两组手术时间、住院时间和骨折愈合时间,以及术中出血量、并发症发生率和骨盆功能恢复优良率。结果:观察组手术时间、住院时间及骨折愈合时间短于对照组,术中出血量少于对照组,差异有统计学意义(t=2.721,t=2.458,t=2.791,t=4.450;P<0.05);观察组和对照组并发症发生率分别为3.33%和10.00%,差异无统计学意义(x²=0.267,P>0.05);观察组和对照组骨盆功能恢复优良率分别为96.67%和73.33%,观察组明显高于对照组,差异有统计学意义(x²=4.705,P<0.05)。结论:复杂骨盆骨折手术中应用3D打印骨折模型可缩短手术时间、住院时间,减少出血量,促进骨折愈合,可改善骨盆功能且并发症少。     

基于网络药理学研究黄连解毒汤抗幽门螺杆菌感染作用机制

目的运用网络药理学方法预测黄连解毒汤抗Hp感染的主要有效成分、靶点及信号通路,挖掘其潜在作用机制,为后续实验研究提供依据。方法应用TCMSP筛选黄连解毒汤中黄连、黄芩、黄柏、栀子4味中药的主要有效成分及其潜在作用靶点。通过GeneCards数据库和人类孟德尔遗传数据库(OMIM)筛选Hp感染相关靶点,并取药物和疾病的交集靶点。将交集靶点导入Cytoscape 3.7.2构建有效成分和Hp感染相关靶点网络,并进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用(PPI)网络并进行分析。运用R语言在线检索Bioconductor平台对靶点进行GO功能富集;通过DAVID数据库对靶点进行KEGG通路富集分析。结果黄连解毒汤中共筛选出85个有效成分,主要包括槲皮素、小檗碱、山柰酚、汉黄芩素、黄芩素等。对应靶点112个,疾病相关靶点1960个,药物疾病共同靶点71个。网络中度值最高的有效成分为槲皮素,度值最高的靶点为环加氧酶1(PTGS1)。PPI网络中69个节点中度值较高的靶蛋白包括半胱氨酸蛋白酶3(CASP3)、IL6、MAPK8、原癌基因(MYC)、VEGFA、表皮生长因子受体(EGFR)等。GO功能富集分析共获得89个条目,KEGG通路富集分析共筛选12条存在显著差异的信号通路,其中发挥主要作用的有癌症通路、ErbB信号通路、p53信号通路、凋亡、黏附斑等。结论黄连解毒汤可通过多成分、多靶点、多通路发挥对Hp的治疗作用,可通过抗肿瘤机制调控胃癌进程,本研究可为其有效成分研究和抗Hp机制研究提供依据。     

儿童腹型过敏性紫癜不同中医证候临床及尿液蛋白质组学差异比较＊

目的 探讨儿童腹型过敏性紫癜（AHSP）不同中医证候的临床及尿液蛋白特征。方法 按照诊断及纳入、排除标准，收集AHSP不同中医证候患儿的临床信息及尿样进行分析，并通过尿液蛋白质组质谱分析，筛选及比较AHSP不同证候的尿液差异蛋白。结果 AHSP不同证候临床特征显示，皮肤紫癜首发者风热伤络证最多，湿毒内蕴证次之；皮肤紫癜伴腹痛症状首发者仅在脾虚不摄证中出现。不同证候间实验室指标未出现统计学差异。通过DDA及DIA定量方法，在不同证候间筛选出21个证候差异蛋白，其中风热伤络、湿毒内蕴证间2个，风热伤络、脾虚不摄证间3个，湿毒内蕴、脾虚不摄证间16个；经OPLS-DA分析筛选出10个差异蛋白，包括ALDOB、Glyc、GSTA2、GPDA、GAPDH、CRYL1、AK1A1、VMO1、Cat S、DHPR。结论 AHSP不同证候间临床及尿液蛋白存在差异，这些差异可为腹型过敏性紫癜的证候诊断提供一定的帮助。     

Retroperitoneal-first laparoscopic approach (Retlap)-assisted distal pancreatectomy with celiac axis resection (DP-CAR): A novel minimally invasive approach for achieving adequate dorsal surgical margin

BackgroundDistal pancreatectomy with celiac axis resection (DP-CAR) is a procedure to secure a surgical margin for a locally advanced pancreatic body cancer that invades the celiac axis. However, in patients with cancer close to the root of the celiac axis, obtaining adequate surgical margins can be difficult because the tumor obstructs the field of vision to the root of the celiac axis. Previously, we described the retroperitoneal-first laparoscopic approach (Retlap) to achieve both accurate evaluation of resectability for locally advanced pancreatic cancer requiring DP-CAR [1] and adequate surgical margin for laparoscopic distal pancreatectomy [2]. In this video, we introduce Retlap-assisted DP-CAR as a minimally invasive approach for performing an artery-first pancreatectomy [3, 4] and achieving sufficient dorsal surgical margin (Fig. 1).MethodsOur patient is a 67-year-old man with a 55 × 29-mm pancreatic body tumor after chemotherapy. Preoperative computed tomography revealed a tumor close to the root of the celiac axis. Because the area of tumor invasion on preoperative images was near the root of the celiac artery, Retlap-assisted DP-CAR was performed to determine whether the celiac axis can be secured and obtain an adequate dorsal surgical margin (Fig. 2).ResultsThe operative time and estimated blood loss was 715 min and 449 mL, respectively. In spite of the advanced tumor's location and size, R0 resection was achieved in a minimally invasive way.ConclusionRetlap-assisted DP-CAR is not only technically feasible and useful for achieving accurate evaluation of resectability but also facilitates obtaining an adequate surgical margin.     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

Extracorporeal membrane oxygenation as a bridge to transplant in neonates with fatal pulmonary conditions: A review

Neonates with progressive respiratory failure should be referred early for subspecialty evaluation and lung transplantation consideration. ECMO should be considered for patients with severe cardiopulmonary dysfunction and a high likelihood of death while on maximal medical therapy, either in the setting of reversible medical conditions or while awaiting lung transplantation. While ECMO offers hope to neonates that experience clinical deterioration while awaiting transplant, the risks and benefits of this intervention should be considered on an individual basis. Owing to the small number of infant lung transplants performed yearly, large studies examining the outcomes of various bridging techniques in this age group do not exist. Multiple single-centre experiences of transplanted neonates have been described and currently serve as guidance for transplant teams. Future investigation of outcomes specific to neonatal transplant recipients bridged with advanced devices is needed.     

The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer’s disease: A narrative review

Alzheimer’s disease (AD) is the most common cause of dementia, accounting for more than 50 million patients worldwide. Current evidence suggests the exact mechanism behind this devastating disease to be of multifactorial origin, which seriously complicates the quest for an effective disease-modifying therapy, as well as impedes the search for strategic preventative measures. Of interest, preclinical studies point to serotonergic alterations, either induced via selective serotonin reuptake inhibitors or serotonin receptor (ant)agonists, in mitigating AD brain neuropathology next to its clinical symptoms, the latter being supported by a handful of human intervention trials. Additionally, a substantial amount of preclinical trials highlight the potential of diet, fecal microbiota transplantations, as well as pre- and probiotics in modulating the brain’s serotonergic neurotransmitter system, starting from the gut. Whether such interventions could truly prevent, reverse or slow down AD progression likewise, should be initially tested in preclinical studies with AD mouse models, including sufficient analytical measurements both in gut and brain. Thereafter, its potential therapeutic effect could be confirmed in rigorously randomized controlled trials in humans, preferentially across the Alzheimer’s continuum, but especially from the prodromal up to the mild stages, where both high adherence to such therapies, as well as sufficient room for noticeable enhancement are feasible still. In the end, such studies might aid in the development of a comprehensive approach to tackle this complex multifactorial disease, since serotonin and its derivatives across the microbiota-gut-brain axis might serve as possible biomarkers of disease progression, next to forming a valuable target in AD drug development. In this narrative review, the available evidence concerning the orchestrating role of serotonin within the microbiota-gut-brain axis in the development of AD is summarized and discussed, and general considerations for future studies are highlighted.