多层螺旋CT后处理技术对小儿气道异物的诊断价值

目的探讨多层螺旋CT后处理技术在小儿气道异物临床诊断中的应用价值。方法对我院39例疑似气道异物患儿行64排CT平扫后利用后处理技术重建图像资料,影像诊断为气道异物,并回访临床支气管镜下异物探查结果进行分析讨论。结果39例患儿中提供异物吸入史的为36例,37例支气管镜下异物探查取出术结果证实为阳性,准确率达95%,2例误诊,误诊率为5%;其中2例出现阻塞性肺炎,右侧支气管21例,左侧支气管15例,支气管分叉处1例。结论根据患儿有无吸入史,结合多层螺旋CT后处理技术后重建图像,对气道异物诊断、定位及临床治疗和预后提供了重要价值。     

Platelets are efficient and protective depots for storage,distribution, and delivery of lysosomal enzyme in mice with Hurler Syndrome

Use of megakaryocytes/platelets for transgene expression may take advantage of their rapid turnover and protective storage in platelets and reduce the risk of activating oncogenes in hematopoietic stem and progenitor cells (HSCs). Here, we show that human megakaryocytic cells could overexpress the lysosomal enzyme, α-l-iduronidase (IDUA), which is deficient in patients with mucopolysaccharidosis type I (MPS I). Upon megakaryocytic differentiation, the amount of released enzyme increased rapidly and steadily by 30-fold. Using a murine MPS I model, we demonstrated that megakaryocyte/platelets were capable of producing, packaging, and storing large amounts of IDUA with proper catalytic activity, lysosomal trafficking, and receptor-mediated uptake. IDUA can be released directly into extracellular space or within microparticles during megakaryocyte maturation or platelet activation, while retaining the capacity for cross-correction in patient’s cells. Gene transfer into 1.7% of HSCs led to long-term normalization of plasma IDUA and preferential distribution of enzyme in liver and spleen with complete metabolic correction in MPS I mice. Detection of GFP (coexpressed with IDUA) in Kupffer cells and hepatocytes suggested liver delivery of platelet-derived IDUA possibly via the clearance pathway for senile platelets. These findings provide proof of concept that cells from megakaryocytic lineage and platelets are capable of generating and storing fully functional lysosomal enzymes and can also lead to efficient delivery of both the enzymes released into the circulation and those protected within platelets/microparticles. This study opens a door for use of the megakaryocytes/platelets as a depot for efficient production, delivery, and effective tissue distribution of lysosomal enzymes.The potential of therapeutic benefits from genetically modified hematopoietic stem cells (HSCs) has been supported in recent gene therapy clinical trials (1, 2). High transgene dosage or selective growth of genetically corrected HSCs appears to be necessary for achieving clinical efficacy. However, genotoxic risk caused by proviral integration-associated oncogenesis is directly concomitant with high numbers of integration events or clonal expansion (3, 4). New approaches are needed to balance the need for high transgene frequency while limiting the associated increased risk of oncogenesis.Platelets are anuclear, secretory particulate entities containing proteins stored in cytoplasmic granules that can be released upon activation (5). Healthy adults produce 2–5 × 10¹¹ platelets daily with a baseline activation rate of 1–5% (6). Use of megakaryocytes (MKs)/platelets for transgene expression may (i) take advantage of this immense cell mass and its rapid turnover (5–9 d); (ii) provide protective storage of the transgene product, which is essential for proteins sensitive to plasma pH; and (iii) continuously dispense proteins via degranulation from platelet activation at baseline (without detectable injury) and/or at sites of vascular injury. Highly efficient protein production and delivery could further reduce the need for high transgene frequency and the risk of activating oncogenes in HSCs and all their progeny. Although using platelets as a delivery system has been demonstrated for the expression of coagulation factors to treat inherited bleeding disorders in mice (7, 8), there has been no report of the feasibility of using MKs/platelets for the generation of nonhematologic proteins.Lysosomal storage diseases (LSDs) are a group of inherited disorders, often affecting multiple organs including the liver and spleen, with a cumulative incidence of 1 in 5,000–7,000 live births (9). Overexpressing lysosomal enzymes in platelets not only can provide the protection of pH-sensitive enzymes and continuous enzyme release via low physiological levels of platelet activation but may also offer the benefit of on-target delivery of platelet-derived enzymes to spleen and liver in the process of platelet clearance (10). However, maintaining proper posttranslational modifications for appropriate lysosomal trafficking and intercellular lysosomal enzyme transfer is essential for metabolic cross correction in treating these multiorgan diseases (11). It is not known whether lysosomal enzymes generated from the MK/platelet lineage would be fully functional and capable of correcting lysosomal deficits in diseased cells.In this study, we used a mouse model of Hurler syndrome, which is the severe form of mucopolysaccharidosis type I (MPS I), one of most common LSDs. It is caused by the deficiency of α-l-iduronidase (IDUA) and consequent accumulation of glycosaminoglycans (GAGs) (12, 13). We show that MKs are capable of producing large amounts of IDUA with proper catalytic function, lysosomal trafficking and receptor-mediated uptake, which could be sorted to and stored within platelets. The IDUA can be released directly into the extracellular space or within microparticles (MPs) during MK maturation or platelet activation, while retaining its ability to cross-correct cells derived from patients with MPS I.     

The validation study of a novel assay with 30 slow and moderate mutation Y-STR markers for criminal investigation and database applications

International Journal of Legal Medicine - The Y chromosome short tandem repeat (Y-STR) haplotyping method has been widely used in forensic applications. However, the existing Y-STR panels are not...     

Low-grade albuminuria is associated with peripheral artery disease in Chinese diabetic patients

Background

Increasing studies have suggested that albuminuria might be an important risk factor for peripheral artery disease (PAD). However, studies focusing on the association between low-grade albuminuria and PAD are limited. It would be of great interest to elucidate the association between low-grade albuminuria and PAD in diabetic subjects.

Methods

A cross-sectional study was conducted in 1386 diabetic subjects (age ≥ 40 years) with normal urinary albumin levels from Shanghai, China. A first voided early morning spot urine sample was obtained for urinary albumin and creatinine measurements. Subjects were divided into three groups according to sex-specific cutoff points of urinary albumin–creatinine ratio (UACR) tertiles. Subjects in the upper tertile of UACR were classified as having low-grade albuminuria. PAD was defined by ankle–brachial index (ABI) <0.9 or >1.4.

Results

Overall, 106 (7.7%) of the study population had PAD. The prevalence of PAD in tertile 3 of UACR was higher than the prevalence in tertile 2 and tertile 1 (10.2%, 6.4% and 6.4%, respectively; P < 0.05). A fully adjusted logistic regression analysis revealed that compared with subjects in tertile 1 of normal UACR, those in tertile 3 had 1.7-fold increased risk for the presence of PAD.

Conclusions

In diabetic patients, high normal UACR level, which is below the current cutoff point of microalbuminuria, was associated with the increased prevalence of PAD. It suggested that low-grade albuminuria might be an early marker for the detection of PAD in diabetic patients.     

头颈部鳞癌程序性死亡配体-1的共表达基因及 调控网络的生物信息学分析

目的 运用生物信息学的方法绘制头颈部鳞癌（HNSCC）中程序性死亡配体-1（PD-L1）共表达基因关系网络,筛选潜在的PD-L1的协同标志物,寻找可能的PD-L1基因调控肿瘤免疫状态的基因和通路。方法 利用癌症和肿瘤基因图谱（TCGA）中的大样本HNSCC的转录组学数据,在cBioPortal数据平台进行基因集的检索,筛选PD-L1共表达基因,在R语言的clusterProfiler中进行GO-BP和KEGG富集分析,再进行分子关系网络分析,提取重要节点基因（hub基因）,再进行生存分析。结果 筛选出共表达基因117个,共表达基因主要富集在免疫调节和病毒反应过程。网络节度分析得到了10个hub基因,依次为STAT1、IFNG、CXCL10、CCR5、FCGR3A、CXCL9、GBP5、CD86、GZMB、IRF1。生存分析显示：CCR5、CXCL9、GZMB是HNSCC预后相关的重要基因。这些基因均参与了免疫过程,其表达与PD-L1相关（Pearson相关系数为0.30、0.35、0.39,P值均小于0.01）。这些基因高表达在HNSCC中均为保护因素。结论 HNSCC中的PD-L1共表达的主要基因均为免疫相关基因,其中CCR5、CXCL9、GZMB与PD-L1存在共表达关系,与预后相关,其可能与程序性死亡受体-1（PD-1）/PD-L1介导的肿瘤免疫逃避相关,为进一步研究PD-1/PD-L1的作用机制和精准靶向治疗提供了新的参考。     

颈部动静脉瘘合并深静脉高压的影像特征分析

目的分析动静脉瘘(AVF)合并深静脉高压的影像特征旨在提高认识。方法回顾性分析1例颈部AVF致颅内深静脉高压病人的临床资料及影像表现,并复习相关文献。结果CT及MRI表现为深静脉高压征象:①双侧基底节丘脑区及脑室旁、左侧小脑肿胀伴血管源性水肿;②深静脉引流区多发细小迂曲血管影及含铁血黄素沉积。DSA显示左侧颈部AVF,动脉期见左侧颈内静脉-乙状窦-横窦-直窦反流。结论AVF临床及影像表现具有多样性,当颅内静脉引流区出现肿胀伴异常信号、多发迂曲血管影时,应及早行血管检查以明确诊断,DSA是确诊该病的金标准。     

Preeclampsia in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis

Clinical Rheumatology - The impact of systemic lupus erythematosus (SLE) on preeclampsia is still obscure. This study was performed to systematically assess the association between preeclampsia and...     

Moyamoya syndrome related to systemic lupus erythematosus developing during pregnancy: a case-based review

Clinical Rheumatology - Moyamoya syndrome (MMS) is a chronic cerebrovascular disorder characterized by occlusion or stenosis of the internal carotid arteries with the formation of abnormal...     

Cross-cultural adaption and validation of simplified Chinese version of the lower extremity function scale in patients with knee osteoarthritis

Clinical Rheumatology - The lower extremity function scale (LEFS) is widely used to investigate patients’ functional status due to musculoskeletal dysfunction of the lower extremity. The aims...