IS6110-PCR分型方法用于安徽、湖南、江苏三省结核病分子流行病学的初步研究

目的了解安徽、湖南、江苏省结核分支杆菌的基因型状况及其分子流行病学规律。方法以结核分枝杆菌插入序列IS6110序列为模板,设计一对特异外向引物,建立一种结核分枝杆菌的快速分子生物学分型方法——IS6110PCR分型方法,进行三省结核病分子流行病学研究。结果根据IS6110PCR指纹图谱,191株安徽、湖南和江苏三省的结核分枝杆菌菌株可被分成6个主要的基因型(Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ和Ⅵ),江苏省的主要基因型为I和V型,安徽省的主要基因型为III型,湖南省的主要基因型为I和II型,V型菌株全部为江苏省菌株,IV型菌株全部为湖南省菌株。结论三省之间结核分支杆菌的基因型存在明显的差异,各自存在着独立的流行菌型,其真实原因有待进一步研究。     

Impaired regeneration in LGMD2A supported by increased PAX7‐positive satellite cell content and muscle‐specific microrna dysregulation

Introduction: Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, up‐regulation of miR‐1 and miR‐206 facilitates transition from proliferating SCs to differentiating myogenic progenitors. Methods: We examined the histopathological stages, Pax7 SC content, and muscle‐specific microRNA expression in biopsy specimens from well‐characterized LGMD 2A patients to gain insight into disease pathogenesis. Results: Three distinct stages of pathological changes were identified that represented the continuum of the dystrophic process from prominent inflammation with necrosis and regeneration to prominent fibrosis, which correlated with age and disease duration. Pax7‐positive SCs were highest in the fibrotic group and correlated with down‐regulation of miR‐1, miR‐133a, and miR‐206. Conclusions: These observations, and other published reports, are consistent with microRNA dysregulation leading to inability of Pax7‐positive SCs to transit from proliferation to differentiation. This results in impaired regeneration and fibrosis. Muscle Nerve 47: 731–739, 2013     

Intracranial vessel wall lesions on 7T MRI and MRI features of cerebral small vessel disease: The SMART-MR study

The etiology of cerebral small vessel disease (CSVD) is the subject of ongoing research. Although intracranial atherosclerosis (ICAS) has been proposed as a possible cause, studies on their relationship remain sparse. We used 7 T vessel wall magnetic resonance imaging (MRI) to study the association between intracranial vessel wall lesions—a neuroimaging marker of ICAS—and MRI features of CSVD. Within the SMART-MR study, cross-sectional analyses were performed in 130 patients (68 ± 9 years; 88% male). ICAS burden—defined as the number of vessel wall lesions—was determined on 7 T vessel wall MRI. CSVD features were determined on 1.5 T and 7 T MRI. Associations between ICAS burden and CSVD features were estimated with linear or modified Poisson regression, adjusted for age, sex, vascular risk factors, and medication use. In 125 patients, ≥1 vessel wall lesions were found (mean 8.5 ± 5.7 lesions). ICAS burden (per + 1 SD) was associated with presence of large subcortical and/or cortical infarcts (RR = 1.65; 95%CI: 1.12–2.43), lacunes (RR = 1.45; 95% CI: 1.14–1.86), cortical microinfarcts (RR = 1.48; 95%CI: 1.13–1.94), and total white matter hyperintensity volume (b = 0.24; 95%CI: 0.02–0.46). Concluding, patients with a higher ICAS burden had more CSVD features, although no evidence of co-location was observed. Further longitudinal studies are required to determine if ICAS precedes development of CSVD.     

Effect of ASCO/CAP Guidelines for Determining ER Status on Molecular Subtype

Background

Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1 % positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype.

Methods

Clinicopathological characteristics were compared between ER-negative, ER-positive, and low-ER-staining (1–10 %) tumors using chi-square analysis with P < 0.05 defining statistical significance. Gene expression data were generated for 26 low-ER-staining tumors, and their intrinsic subtype determined. Immunohistochemistry (IHC)-defined surrogate subtypes, using the threshold of positivity defined by ASCO/CAP guidelines, were compared with molecular subtypes.

Results

Low-ER-staining tumors were clinicopathologically more similar to ER-negative than to ER-positive tumors; 88 % of low-staining tumors were basal like or HER2 enriched. Only those tumors expressing 10 % ER-positive cells were classified as luminal A subtype.

Conclusions

Under ASCO/CAP guidelines, tumors with 1–10 % ER staining would be classified as ER positive, yet most are basal like or HER2 enriched and have pathological features similar to ER-negative tumors. Clinical trials seeking to treat tumors of ER-negative basal-like and/or HER2-enriched subtypes should thus not preclude enrollment based solely on results of ER immunohistochemistry. As ER status is a critical element in the choice of treatments for patients with breast cancer, it is imperative that the most effective method for classifying tumors be developed.     

Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease – Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1–49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate −0.03; 95%CI, −0.06 to −0.01; p = 0.002), and a greater decline in executive functioning (estimate −0.02; 95%CI, −0.031 to −0.01; p < 0.001) and memory (estimate −0.012; 95%CI, −0.02 to −0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline.     

苯乙哌啶合成的改进

目的：改进苯乙哌啶的合成方法,使之更适合工业化生产。方法,以N,N－双（β-氯乙基）对甲苯磺酰胺为原料,利用液－液相转移催化方法制得1－对甲苯磺酰基－4－氰基哌啶,再经水解,酯化,缩合,成盐等步骤,合成了苯乙哌啶。结果：总收率可达51．8％,结论：此合成方法适合工业化生产。     

Hematoxylin and Safranin O Staining of Frozen Sections

Currently the hematoxylin and eosin staining procedure is the most popular among Mohs surgeons for histology. However, safranin O, a cheaper and relatively safer stain which is predominantly used for plant histology, should be considered as it offers similar or improved accuracy in the diagnosis of frozen sections of basal and squamous cell carcinomas.     

萘甲异喹对离体豚鼠心肌的作用

萘甲异喹(NI)呈浓度依赖性地降低离体豚鼠心房收缩力和频率。其拮抗豚鼠左房肌Iso正性肌力作用的PD2₂′值为5.4,Ver为5.8。NI10μmol/L明显降低豚鼠乳头肌收缩力;缩短快反应APD,以对APD₂₀影响最大,但不影响APA和V_max。对高K⁺去极化慢反应动作电位,NI产生浓度依赖性负性肌力作用,同时明显降低APA,V_max,缩短APD;提高细胞外液Ca²⁺浓度可使其抑制作用逆转。结果提示NI具有钙通道阻滞作用。     

Volume calculation by means of SPECT: analysis of imaging acquisition and processing factors

To assess the effect of image acquisition and processing factors on the volume calculated from single photon emission computed tomography (SPECT) images, the authors evaluated technical factors including image matrix size, size of the region of interest (ROI), activity concentration in the region, amount of background subtraction, type of reconstruction filter, section thickness, and number of projections. They found that the percentage of background subtraction was the single most important factor affecting volume calculation. The smaller the volume, the greater the amount of background subtraction needed before the ROI is drawn. As an acceptable means to circumvent the varying percentage of background subtraction for different volumes, a calibration curve was constructed relating the true volume with the calculated volume for a fixed percentage of background subtraction. The use of a 128 X 128 acquisition matrix and zooming of the reconstructed images were necessary for accurate calculation of volumes smaller than 300 mL.     

毛梗稀莶抗生育活性成分的研究

自菊科植物毛梗豨莶Siegesbeckia glabrescens Mak的全草中分得一个新的二萜甙,命名为豨莶新甙(neodarutoside),经光谱(IR,¹ HNMR,¹³ CNMR和MS)分析,确定结构为(I);同时分得的二萜有豨莶精醇(darutigenol,Ⅳ)和豨莶甙(d&rutoside,Ⅴ)。豨莶甙(Ⅴ)在20～40 mg/kg剂量时,对大鼠有明显抗早孕作用。