A multi-center study of using carbon nanoparticles to track lymph node metastasis in T1–2 colorectal cancer

Background

How to identify whether T1–2 colorectal cancers have lymph nodes metastases pre-op or intra-op is a crucial problem in clinic. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to track lymph nodes metastases in T1–2 colorectal cancers.

Methods

A multi-center study was performed between July 2012 and January 2014. Seventy-three patients with T1–2 colorectal cancer identified by pre-op endoscopic ultrasonography (EUS) were recruited. 1 ml carbon nanoparticles suspension was endoscopically injected into the submucosal layer at four points around the site of the primary tumor 1 day before surgery. Laparoscopic radical resection with lymphadenectomy was performed. Sentinel lymph nodes (SLNs) were defined as nodes that were black-dyed by carbon nanoparticles. Pathology confirmed whether lymph nodes have cancer metastases and the SLNs accuracy.

Results

SLNs were easily found under laparoscopy. The mean number of SLNs was 3 (range 1–5). All patients had SLNs lying alongside the mesenteric vessel or main arterial vessel. After pathological analysis, 2 patients (9.52 %) had lymph node metastasis in 21 patients with EUS T1 cancers, and 10 patients (19.23 %) had lymph node metastasis in 52 patients with EUS T2 cancers. In two T1 cases with lymph node metastasis, SLNs were positive with 100 % accuracy. In ten T2 cases with lymph node metastasis, SLNs were positive in nine cases. In pathology, carbon nanoparticles were seen in lymphatic vessels, and lymphoid sinus and macrophages in negative SLNs. When SLNs were positive, carbon nanoparticles were seen around cancer cells in lymph nodes. The overall sensitivity, specificity, accuracy of SLNs in T1–2 colorectal cancers were 91.67, 100, 98.63 %, respectively.

Conclusions

We demonstrated the feasibility of using carbon nanoparticles to track lymph nodes metastases in T1–2 colorectal cancers. Carbon nanoparticles black-dyed lymph nodes play a role as SLNs in T1–2 colorectal cancers.     

Bayesian random effects selection in mixed accelerated failure time model for interval‐censored data

In many medical problems that collect multiple observations per subject, the time to an event is often of interest. Sometimes, the occurrence of the event can be recorded at regular intervals leading to interval‐censored data. It is further desirable to obtain the most parsimonious model in order to increase predictive power and to obtain ease of interpretation. Variable selection and often random effects selection in case of clustered data become crucial in such applications. We propose a Bayesian method for random effects selection in mixed effects accelerated failure time (AFT) models. The proposed method relies on the Cholesky decomposition on the random effects covariance matrix and the parameter‐expansion method for the selection of random effects. The Dirichlet prior is used to model the uncertainty in the random effects. The error distribution for the accelerated failure time model has been specified using a Gaussian mixture to allow flexible error density and prediction of the survival and hazard functions. We demonstrate the model using extensive simulations and the Signal Tandmobiel Study^®. Copyright © 2013 John Wiley & Sons, Ltd.     

Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug “Tianma” (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.KEY WORDS: Borneol, Gastrodin, Oral drug delivery, Brain-targeting, Gastric mucosa irritation, Sustained-release     

The association of the UHRF1BP1 gene with systemic lupus erythematosus was replicated in a Han Chinese population from mainland China

Single-nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome-wide association study (GWAS) data of SLE (1,047 cases and 1,205 controls from a mainland Han Chinese population) to explore the association between the UHRF1BP1 gene and SLE. We conducted a large-scale replication study in an additional independent sample of 3,509 cases and 8,246 controls from a mainland Han Chinese population. Real-time PCR was used to determine gene expression differences in peripheral blood mononuclear cells (PBMCs) from cases and controls. As a result, we replicated the association between the UHRF1BP1 gene and SLE (rs13205210, missense, P_meta = 2.26E-17, odds ratio = 1.41) by a meta-analysis of our previous GWAS and this replication study involving a total of 4,556 cases and 9,451 controls. The UHRF1BP1 mRNA expression level in PBMCs was significantly decreased in patients with SLE compared with that in healthy controls. SNP rs13205210 exhibited an expression quantitative trait loci effect on the UHRF1BP1 gene in PBMCs from patients. In conclusion, this study not only suggests that the UHRF1BP1 gene was associated with SLE in a mainland Han Chinese population, but also implied that it might be a common genetic factor contributing to SLE susceptibility in multiple populations.     

艰难梭菌毒素B诱导结肠癌细胞凋亡及相关机制研究

目的检测艰难梭菌毒素B(TcdB)对结肠癌SW480细胞增殖与凋亡的影响,研究其引起细胞凋亡的相关机制。方法采用不同浓度的TcdB处理SW480细胞,采用MTT法检测细胞增殖情况;用流式细胞术检测细胞的凋亡及线粒体膜电位变化情况。结果TcdB显著抑制了结肠癌SW480细胞的增殖,作用48 h后的抑制率为46.36%,呈一定的时间-浓度相关性;流式细胞仪检测结果表明,浓度为800 ng/ml的TcdB作用48 h,SW480细胞凋亡率为20.83%,呈一定的时间-浓度相关性。结论艰难梭菌毒素B能够抑制结肠癌SW480细胞增殖、诱导细胞凋亡,其机制可能与启动线粒体凋亡途径有关。     

骨髓增生异常综合征患者的asxli基因变异分析

目的探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者ASXL1基因变异的发生情况及其与其他基因变异和部分临床参数之间的相关性。方法采用PCR扩增产物直接测序法检测149例MDS患者ASXU、U2AF1、SF3B1、DNMT3A、TET2、IDH1/2、NPM1、FLT3-ITD.C-KIT等基因的变异情况。结果在149例患者中,ASXU基因变异的检出率为24.8%(37/149),变异率>5%的基因分别是U2AF1(22.8%)、TET2(11.4%)、DNMT3A(9.4%)、NPM1(8.1%).SF3B1(6.0%)。ASXL1变异最常见的共存变异基因为U2AF1(27.0%,10/37)及TET2(18.9%,7/37)。ASXL1变异组与野生组患者在中位年龄、MDS亚型、染色体核型、外周白细胞、血红蛋白、血小板水平及骨髓原始细胞计数等方面的差异均无统计学意义(P>0.05)o对29例ASXL1变异患者进行了有效的随访,其中11例进展为急性髓系白血病(acute myeloid leukemia,AML),白血病转化率为37.9%。在92例野生型患者中,13例进展为AML,白血病转化率为14.1%。ASXL1变异组白血病转化率明显高于野生组,差异有统计学意义(PV 0.01)。结论ASXL1变异在MDS中有较高的发生率,并常与U2AF1及TET2基因变异共存,伴有该变异的患者具有更高的白血病转化率。     

Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome

Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin‐2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant‐negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS‐disease gene and expands its clinical and genetic spectrum to include recessive loss‐of‐function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications.     

后外上方单侧穿刺椎体成形术治疗骨质疏松椎体压缩骨折的安全性及有效性

目的 评估后外上方入路单侧穿刺行椎体成形术(PVP)治疗骨质疏松性椎体压缩骨折(OVCF)的安全性和有效性。方法 回顾性分析自2017年9月至2018年9月本科收治的109例(144个椎体)骨质疏松性椎体压缩骨折患者资料,平均年龄(76.7±9.9)岁(55～96岁),采用后外上方单侧穿刺入路行椎体成形术进行治疗。记录手术时间、注入的骨水泥体积、并发症发生率、视觉疼痛模拟量表(VAS)、Oswestry残疾指数(ODI)评分、穿刺针尖端的最终位置以及聚甲基丙烯酸甲酯(PMMA)骨水泥在椎体中的扩散。结果 所有患者均成功完成手术,平均随访(9.1±2.9)个月。每个骨折椎体的平均手术时间为(24.0±3.5) min。注入骨水泥的平均体积为(4.8±0.6) m L。术前平均VAS评分为(8.4±0.7)分,术后1 d为(1.6±0.6)分,末次随访为(1.2±0.6)分。术前ODI平均得分为(70.97±7.73)分,术后1 d为(27.99±4.12)分,末次随访为(19.65±3.49)分。穿刺针尖端的最终位置:119根穿刺针到达中线,15根接近中线,10根超过中线。骨水泥在椎体中的分布类型:81例为类型1(56.3%),37例为类型2(25.7%),18例为类型3(12.5%),8例为类型5(5.5%),无病例为类型4。1例术后出现气胸,无其他并发症(如血肿、骨水泥栓塞、脊髓及神经损伤)。结论 椎体后外上方入路单侧穿刺的椎体成形术,可较为方便地穿刺至椎体中线,获得良好的骨水泥弥散,是治疗骨质疏松椎体压缩骨折的一种安全、有效方法。