微创缝合联合术后早期加速康复治疗急性跟腱断裂的临床研究

目的 探讨利用自制缝线引导钳通过小切口微创缝合技术联合术后加速康复治疗急性跟腱断裂的方法和疗效.方法 前瞻性分析2015年10月—2017年4月中部战区总医院足踝与运动医学中心收治的跟腱断裂患者63例,男性55例,女性8例;年龄14～61岁,平均38.5岁;其中借助自制的缝线引导钳,通过小切口微创缝合技术治疗急性闭合性跟腱断裂患者38例,按照随机数字表法分为加速组(20例)和常规组(18例).两组采取不同的术后方案:加速组术后短腿支具固定踝关节于中立位(背屈0°),术后3d即开始膝关节屈曲90°进行主动踝关节屈伸练习(踝背屈限制在0°),术后2～4周去除短腿支具,主动踝关节全范围屈伸练习,可穿戴行走靴部分负重逐渐过渡到完全负重;常规组短腿支具固定踝关节于跖屈30°,术后3d开始练习屈伸膝关节;术后4周～3个月开始膝关节屈曲90°位主动踝关节屈伸练习,穿戴行走靴逐渐过渡到完全负重.采用美国足与踝外科协会(AOFAS)踝与后足功能评分标准进行评分,询问恢复到伤前体育活动水平的时间.结果 两组患者均未出现跟腱再断裂、切口深部感染、皮瓣坏死等.加速组切口浅表感染2例,腓肠神经损伤1例;常规组切口浅表感染1例,无腓肠神经损伤病例.术后1年AOFAS评分:加速组85～100分,平均94.3分;常规组83～95分,平均92.6分.重返运动情况:加速组15例(88.2％)恢复到伤前的运动水平,重返运动时间20～24周,平均21.0周;常规组11例(73.3％)恢复至伤前运动水平,重返运动时间22～27周,平均23.4周.结论 借助自制的缝线引导钳,通过小切口微创缝合技术修复急性跟腱断裂同时联合术后早期加速功能康复可获得满意的临床效果,且可缩短患者重返运动时间.     

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1^highYWHAZ^high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death     

Novel genetic variants in KIF16B and NEDD4L in the endosome-related genes are associated with nonsmall cell lung cancer survival

The endosome is a membrane-bound organ inside most eukaryotic cells, playing an important role in adaptive immunity by delivering endocytosed antigens to both MHC class I and II pathways. Here, by analyzing genotyping data from two published genome-wide association studies (GWASs), we evaluated associations between genetic variants in the endosome-related gene-set and survival of patients with nonsmall cell lung cancer (NSCLC). The discovery included 44,112 (3,478 genotyped and 40,634 imputed) single-nucleotide polymorphisms (SNPs) in 220 genes in a singlelocus analysis for their associations with survival of 1,185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. After validation of the 821 survival-associated significant SNPs in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study, 14 SNPs remained significant. The final multivariate stepwise Cox proportional hazards regression modeling of the PLCO dataset identified three potentially functional and independent SNPs (i.e., KIF16B rs1555195 C>T, NEDD4L rs11660748 A>G and rs73440898 A>G) with an adjusted hazards ratio (HR) of 0.86 (95% confidence interval [CI] = 0.79–0.94, p = 0.0007), 1.31 (1.16–1.47, p = 6.0 × 10⁻⁵) and 1.27 (1.12–1.44, p = 0.0001) for overall survival (OS), respectively. Combined analysis of the adverse genotypes of these three SNPs revealed a trend in the genotype-survival association (p_trend < 0.0001 for OS and p_trend < 0.0001 for disease-specific survival). Furthermore, the survival-associated KIF16B rs1555195T allele was significantly associated with decreased mRNA expression levels of KIF16B in both lung tissues and blood cells. Therefore, genetic variants of the endosome-related genes may be biomarker for NSCLC survival, possibly through modulating the expression of corresponding genes.     

Score confidence intervals and sample sizes for stratified comparisons of binomial proportions

In a series of articles, Gart and Nam construct the efficient score tests and confidence intervals with or without skewness correction for stratified comparisons of binomial proportions on the risk difference, relative risk, and odds ratio effect metrics. However, the stratified score methods and their properties are not well understood. We rederive the efficient score tests, which reveals their theoretical relationship with the contrast-based score tests, and provides a basis for adapting the method by using other weighting schemes. The inverse variance weight is optimal for a common treatment effect in large samples. We explore the behavior of the score approach in the presence of extreme outcomes when either no or all subjects in some strata are responders, and provide guidance on the choice of weights in the analysis of rare events. The score method is recommended for studies with a small number of moderate or large sized strata. A general framework is proposed to calculate the asymptotic power and sample size for the score test in superiority, noninferiority and equivalence clinical trials, or case-control studies. We also describe a nearly exact procedure that underestimates the exact power, but the degree of underestimation can be controlled to a negligible level. The proposed methods are illustrated by numerical examples.     

Review of imaging and endovascular intervention of iliocaval venous compression syndrome

Iliocaval venous compression syndrome (ICS) is the extrinsic compression of the common iliac vein by the overlying iliac artery against the vertebra. Chronic compression can lead to venous stenosis and stasis, which manifests as chronic venous disease and treatment resistance. Therefore, early recognition of ICS and prompt treatment are essential. Clinical presentations of ICS can be ambiguous and diagnosis requires a high index of suspicion with the relevant imaging studies. The initial imaging test is typically a Duplex ultrasound for vessel assessment and pelvic ultrasound to exclude a compressive mass, which is followed by computed tomography (CT) or magnetic resonance (MR) venography. CT and MRI can identify the anatomical causes for venous compression. In patients with high clinical suspicion for ICS, negative findings on CT and MR venography would still warrant further investigations. Definitive diagnosis can be established using catheter-based venography complemented with intravascular ultrasonography but the nature of their invasiveness limits its utility as a routine imaging modality. In this review paper, we will discuss the evidence, utility and limitations of the existing imaging modalities and endovascular intervention used in the management of ICS.     

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

重型血友病A患儿关节出血与关节评估的相关性研究

目的了解血友病患儿出血与关节病变之间的关系,为临床治疗和预后判断提供理论依据。方法选取2016年6月至2017年1月于首都医科大学附属北京儿童医院及成都市新世纪妇女儿童医院就诊的1~7岁重型血友病A且有关节出血记录的患儿,以患儿关节出血为研究关节,收集前3个月研究关节的出血次数,应用超声、X线、磁共振成像(MRI)和血友病关节健康评分(HJHS)评分系统对关节进行评估。将关节出血次数与超声、X线、MRI和HJHS评分进行相关性分析,并对超声、X线、MRI和HJHS评分间的相关性进行分析。结果1.共收集重型血友病A患儿18例,年龄(5.6±1.8)岁,共30个出血关节,中位年关节出血次数为4次(4~16次),中位年靶关节出血次数为8次(4~16次)。2.关节出血次数与超声、X线评估有相关性(r=0.390,P=0.033;r=0.517,P=0.008),与HJHS评估、MRI评估均无相关性(均P>0.05)。3.超声、X射线、HJHS和MRI两两之间均呈极显著正相关[r=0.815(超声与X线),r=0.510(超声与HJHS),r=0.812(超声与MRI),r=0.666(X线与HJHS),r=0.911(X线与MRI),r=0.781(HJHS与MRI),均P<0.01]。4.关节超声和/或MRI评估异常的关节中,出血次数与关节评估间均无相关性(P>0.05)。结论关节出血与关节评估获得的关节病变程度结果不一致,因此准确判断关节病变情况需综合评估关节结构、功能等,以便更加全面地指导血友病患儿的治疗。