Thoracolumbar spinal tuberculosis in children with severe post-tubercular kyphotic deformities treated by single-stage closing–opening wedge osteotomy: preliminary report a 4-year follow-up of 12 patients

Purpose

The correction of severe post-tubercular kyphosis (PTK) is complex and has the disadvantage of being multistaged with a high morbidity. In this study, we evaluated the outcomes of children who underwent single-stage closing–opening wedge osteotomy as a surgical treatment of PTK of the thoracolumbar spine.

Method

Our study group included 12 children with thoracolumbar PTK (seven boys and five girls) with an average age of 9.4 years (range 6–12 years), who were treated at our institution from January 2004 to October 2009. The American Spinal Injury Association Impairment Scale and visual analog scale score were used to classify neurologic function. All patients underwent halo-pelvic traction before surgery and were treated with single-stage closing–opening wedge osteotomy.

Result

The duration of surgery averaged 99 min (range 70–150 min). Average blood loss was 782 ml (range 560–1,200 ml), and the average length of hospital stay was 12 days (range 8–16 days). The neurological function of all patients improved significantly after the procedure. The mean preoperative kyphotic angle was 83.3° (range 59–118°), which had reduced to 27.6° (range 20–38°) at the final follow-up visit. All patients had solid fusion, and no major complications were observed through the final follow-up visit.

Conclusion

Single-stage closing–opening wedge osteotomy is an effective method to correct severe thoracolumbar PTK. A main advantage of the procedure is that it is a posterior-only, single-staged surgery, allowing for significant correction with minimal complications.     

新型咽鼓管吹张法在儿童分泌性中耳炎的应用

目的探讨新型咽鼓管吹张法对儿童分泌性中耳炎的治疗效果。方法将90例分泌性中耳炎患儿按照随机数字表分为对照组和观察组各45例。观察组采用新型咽鼓管吹张法治疗,对照组采用传统的波氏球咽鼓管吹张法治疗,观察记录治疗3个月后两组患儿声阻抗检测变化及患儿的舒适度。结果治疗3个月后两组患儿的声阻抗检测结果及舒适度比较,差异有统计学意义(P0.05,P0.01)。结论新型咽鼓管吹张法能提高患儿操作时的舒适度,增加患儿治疗的信心,提高疾病治疗效果。     

头颈部恶性肿瘤患者全麻术后早期体位的研究

目的探讨头颈部恶性肿瘤全麻术后患者早期适宜的体位。方法将头颈部恶性肿瘤全麻术后患者139例采用随机数字表法分成A组、B组、C组,术后早期A组46例取去枕平卧位,B组46例取半卧位,C组47例循序渐进抬高床头至半卧位。观察三组患者的生命体征、血气分析结果、疼痛(头部、肩颈部及腰背部疼痛)、恶心、呕吐、排尿困难、颜面部水肿及术后下床活动等情况,调查患者的舒适度。结果三组头痛、肩颈部疼痛、腰背部疼痛发生情况及疼痛程度比较,差异有统计学意义(均P0.05),三组呕吐、排尿困难、颜面部水肿发生率及术后下床活动时间比较,差异有统计学意义(P0.05,P0.01),三组生命体征、血气分析、恶心等方面比较,差异无统计学意义(均P0.05)。结论头颈部恶性肿瘤患者全麻术后早期,采用循序渐进的方式抬高床头至半卧位,在保证患者生命体征稳定、不增加呕吐窒息概率的情况下,既可减轻疼痛,预防并发症,还可增加患者的舒适度,促使患者早日下床活动。     

Molecular Surface of JZTX-V (β-Theraphotoxin-Cj2a) Interacting with Voltage-Gated Sodium Channel Subtype NaV1.4

Voltage-gated sodium channels (VGSCs; Na_V1.1–Na_V1.9) have been proven to be critical in controlling the function of excitable cells, and human genetic evidence shows that aberrant function of these channels causes channelopathies, including epilepsy, arrhythmia, paralytic myotonia, and pain. The effects of peptide toxins, especially those isolated from spider venom, have shed light on the structure–function relationship of these channels. However, most of these toxins have not been analyzed in detail. In particular, the bioactive faces of these toxins have not been determined. Jingzhaotoxin (JZTX)-V (also known as β-theraphotoxin-Cj2a) is a 29-amino acid peptide toxin isolated from the venom of the spider Chilobrachys jingzhao. JZTX-V adopts an inhibitory cysteine knot (ICK) motif and has an inhibitory effect on voltage-gated sodium and potassium channels. Previous experiments have shown that JZTX-V has an inhibitory effect on TTX-S and TTX-R sodium currents on rat DRG cells with IC₅₀ values of 27.6 and 30.2 nM, respectively, and is able to shift the activation and inactivation curves to the depolarizing and the hyperpolarizing direction, respectively. Here, we show that JZTX-V has a much stronger inhibitory effect on Na_V1.4, the isoform of voltage-gated sodium channels predominantly expressed in skeletal muscle cells, with an IC₅₀ value of 5.12 nM, compared with IC₅₀ values of 61.7–2700 nM for other heterologously expressed Na_V1 subtypes. Furthermore, we investigated the bioactive surface of JZTX-V by alanine-scanning the effect of toxin on Na_V1.4 and demonstrate that the bioactive face of JZTX-V is composed of three hydrophobic (W5, M6, and W7) and two cationic (R20 and K22) residues. Our results establish that, consistent with previous assumptions, JZTX-V is a Janus-faced toxin which may be a useful tool for the further investigation of the structure and function of sodium channels.     

Three new shRNA expression vectors targeting the CYP3A4 coding sequence to inhibit its expression

RNA interference (RNAi) is useful for selective gene silencing. Cytochrome P450 3A4 (CYP3A4), which metabolizes approximately 50% of drugs in clinical use, plays an important role in drug metabolism. In this study, we aimed to develop a short hairpin RNA (shRNA) to modulate CYP3A4 expression. Three new shRNAs (S1, S2 and S3) were designed to target the coding sequence (CDS) of CYP3A4, cloned into a shRNA expression vector, and tested in different cells. The mixture of three shRNAs produced optimal reduction (55%) in CYP3A4 CDS-luciferase activity in both CHL and HEK293 cells. Endogenous CYP3A4 expression in HepG2 cells was decreased about 50% at both mRNA and protein level after transfection of the mixture of three shRNAs. In contrast, CYP3A5 gene expression was not altered by the shRNAs, supporting the selectivity of CYP3A4 shRNAs. In addition, HepG2 cells transfected with CYP3A4 shRNAs were less sensitive to Ginkgolic acids, whose toxic metabolites are produced by CYP3A4. These results demonstrate that vector-based shRNAs could modulate CYP3A4 expression in cells through their actions on CYP3A4 CDS, and CYP3A4 shRNAs may be utilized to define the role of CYP3A4 in drug metabolism and toxicity.KEY WORDS: RNAi, Cytochrome P450, CYP3A4, shRNA, Chemosensitivity     

64例儿童门静脉高压肝脏病理学分析

目的探讨儿童门静脉高压的临床病理特征。方法对64例儿童门静脉高压的临床情况及肝组织病理形态进行分析。结果64例儿童门静脉高压患儿年龄从1岁3个月至14岁,平均年龄6.3岁。病程2 d至8年,临床主要表现为消化道出血50例(78.1%);脾肿大59例;肝肿大5例;发热8例。B超及CT检查提示门静脉海绵变性57例(89.1%);脾大59例(92.2%);8例提示肝硬化。病理学检查,57例门静脉海绵变性肝脏组织主要表现为门静脉高压的压力相关性形态学改变,其中6例合并其他肝脏病变。7例肝性门静脉高压中包含先天性肝纤维化2例,小结节性肝硬化2例,肝外胆道闭锁致胆汁性肝硬化1例,结节再生性增生1例,非硬化性门静脉高压1例。54例获得随访。结论儿童门静脉高压病因与成人不同,肝组织活检是确诊的重要手段。     

High-coverage SARS-CoV-2 genome sequences acquired by target capture sequencing

In this study, we designed a set of SARS-CoV-2 enrichment probes to increase the capacity for sequence-based virus detection and obtain the comprehensive genome sequence at the same time. This universal SARS-CoV-2 enrichment probe set contains 502 120 nt single-stranded DNA biotin-labeled probes designed based on all available SARS-CoV-2 viral sequences and it can be used to enrich for SARS-CoV-2 sequences without prior knowledge of type or subtype. Following the CDC health and safety guidelines, marked enrichment was demonstrated in a virus strain sample from cell culture, three nasopharyngeal swab samples (cycle threshold [C_t] values: 32.36, 36.72, and 38.44) from patients diagnosed with COVID-19 (positive control) and four throat swab samples from patients without COVID-19 (negative controls), respectively. Moreover, based on these high-quality sequences, we discuss the heterozygosity and viral expression during coronavirus replication and its phylogenetic relationship with other selected high-quality samples from the Genome Variation Map. Therefore, this universal SARS-CoV-2 enrichment probe system can capture and enrich SARS-CoV-2 viral sequences selectively and effectively in different samples, especially clinical swab samples with a relatively low concentration of viral particles.     

抗生素诱导的肠道菌群失调加重小鼠肺炎支原体感染

目的初步探讨抗生素诱导的肠道菌群失调对肺炎支原体(Mycoplasma pneumoniae,Mp)呼吸道感染的影响。方法C57BL/6J小鼠口服万古霉素和庆大霉素21 d后滴鼻感染Mp。实时荧光定量PCR(qPCR)分析抗生素处理前后小鼠粪便中5个主要菌门的菌量;qPCR检测感染后3 d和7 d肺组织中Mp载量;病理切片和HE染色分析肺组织炎症病理改变;流式细胞术分析小鼠脾脏T淋巴细胞分泌的IFN-γ和IL-4;间接ELISA检测Mp特异性IgM和IgG。结果口服万古霉素和庆大霉素后小鼠粪便中拟杆菌门菌量显著减少,厚壁菌门菌量增多,δ,γ变形杆菌门、放线菌门和软壁菌门菌量亦发生改变;口服抗生素小鼠感染Mp后3 d和7 d肺组织Mp载量和炎症病理评分增加,7 d小鼠脾淋巴细胞中分泌IFN-γ的CD4+T细胞减少。结论抗生素诱导的小鼠肠道菌群失调可加重Mp呼吸道感染。     

数据驱动的三叉神经纤维束自动分割算法

目前三叉神经的纤维跟踪成像过程中普遍存在人工依赖性问题,主要包括人工绘制感兴趣区域(ROI)及手动筛选目标纤维束,导致结果的不确定性和数据误差。针对此类问题,提出一种数据驱动的三叉神经纤维自动分割算法。利用多组大脑样本的纤维数据,建立数据驱动的纤维聚类图谱,实现新样本纤维数据的自动分割,直接得到三叉神经纤维束。在实验中,选择25组青年健康人的数据作为样本数据。首先,利用FSL软件分割工具提取脑干作为ROI,进行确定性纤维跟踪。其次,通过对20组纤维数据进行多样本配准和谱聚类,创建数据驱动的纤维聚类图谱。根据三叉神经细小的特点,在建立纤维图谱过程中,通过对脑干纤维束进行二次分类来标注三叉神经纤维束。最后,选择5组青年健康人的新样本数据,将其脑干纤维数据应用纤维图谱自动分割得到三叉神经纤维束,并计算同一样本数据的自动分割结果与手动分割结果之间的加权Dice系数。结果显示,所提出的方法成功分割5组数据的三叉神经纤维束,而传统人工方法成功识别4组三叉神经纤维束,两者结果之间的加权Dice系数分别为0.865,0.939,0.824,0.942。该方法可以有效避免人为因素的影响,提高神经外科医生与颅神经研究者的工作效率。