In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies macro‐ and microstructural changes in neurodegenerative diseases. Previous studies have shown that MR diffusion tensor imaging (DTI) can observe changes in spinal cord white matter in animals and humans affected with symptomatic amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to investigate the sensitivity of DTI for the detection of signs of tissue damage before symptoms appear. High‐field MRI data were acquired using a 9.4‐T animal scanner to examine the spinal cord of an ALS mouse model at pre‐ and post‐symptomatic stages (days 80 and 120, respectively). The MRI results were validated using yellow fluorescent protein (YFP) via optical microscopy of spinal cord tissue slices collected from the YFP,G93A‐SOD1 mouse strain. DTI maps of diffusion‐weighted imaging (DWI) signal intensity, mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were computed for axial slices of the lumbar region of the spinal cord. Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5% decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80). These differences were correlated with changes in axonal fluorescence intensity and membrane cellular markers. This study demonstrates the value of DTI as a potential tool to detect the underlying pathological progression associated with ALS, and may accelerate the discovery of therapeutic strategies for patients with this disease.     

温阳补肾法治疗骨质疏松性骨折

目的 探讨温阳补肾法治疗骨质疏松性骨折对患者疼痛介质及血清sVCAM-1、PDGF、BGP水平的影响.方法 选择骨质疏松性骨折患者106例作为研究对象,通过随机数字表法分为研究组与对照组,各53例.对照组采用常规保守治疗,研究组在对照组的基础上予温阳补肾法进行治疗,2组均治疗3个月.比较2组治疗3个月后的临床疗效;对比2组治疗前、治疗3个月后的骨痂生长评分、中医证候积分、血清疼痛介质及骨代谢指标水平.结果 治疗3个月后,研究组总有效率(96.23％,51/53)高于对照组(75.47％,40/53)(P<0.05).治疗3个月后,2组骨痂生长评分、中医证候积分、血清PGE2、5-HT、NO、sVCAM-1水平较治疗前降低,研究组低于对照组(P<0.05);2组血清PDGF、BGP水平较治疗前升高,研究组高于对照组(P<0.05).结论 温阳补肾法治疗骨质疏松性骨折,可明显降低患者血清疼痛介质水平,减轻疼痛,并能降低血清sVCAM-1水平,升高血清PDGF、BGP水平,促进骨折愈合,有助于提高临床疗效.     

Precise engineering of cetuximab encapsulated gadollium nanoassemblies: in vitro ultrasound diagnosis and in vivo thyroid cancer therapy

We report the formulation of nanoassemblies (NAs) comprising C225 conjugates Gd-PFH-NAs (C-Gd-PFH-NAs) for low-intensity focused ultrasound diagnosis ablation of thyroid cancer. C-Gd-PFH-NAs showed excellent stability in water, phosphate-buffered saline (PBS), and 20% rat serum. Transmission electron microscopy (TEM) images also revealed the effective construction of C-Gd-PFH-NAs as common spherical assemblies. The incubation of C625 thyroid carcinoma with C-Gd-PFH-NAs triggers apoptosis, as confirmed by flow cytometry analysis. The C-Gd-PFH-NAs exhibited antitumor efficacy in human thyroid carcinoma xenografts, where histopathological results further confirmed these outcomes. Furthermore, we were able to use low-intensity focused ultrasound diagnosis imaging (LIFUS) to examine the efficiency of C-Gd-PFH-NAs in thyroid carcinoma in vivo. These findings clearly show that the use of LIFUS agents with high performance imaging in different therapeutic settings will have extensive potential for future biomedical applications.     

阿尔茨海默病病人家属心理负担及影响因素的研究进展

对阿尔茨海默病病人家属产生负面心理负担的原因及影响因素进行综述,以期为解决病人家属心理问题,为提高病人生活质量提供理论依据和参考。     

O2O互动型教学模式在住院医师规范化培训中的应用

目的探讨线上线下（online to offline，O2O）互动型教学模式在住院医师规范化培训中的应用效果。方法以首都医科大学宣武医院医师规范化培训的36名学生作为试验组，每组成员6〖FGS〗~〖FGN〗8人，另外36名前期住院医师作为对照组，试验组采用O2O互动教学法，对照组按照传统教学模式。教学完成后比较两组理论和临床实践技能成绩以及问卷调查结果。结果试验组理论和临床实践技能成绩均优于对照组（P<0.05）,且各项效果评价也优于对照组（P<0.05）。结论O2O互动型教学模式能够为住院医师规范化培训教学提供更优化的教学。     

Melatonin promotes sorafenib‐induced apoptosis through synergistic activation of JNK/c‐jun pathway in human hepatocellular carcinoma

Melatonin has been shown to exert anticancer activity on hepatocellular carcinoma (HCC) through its antiproliferative and pro‐apoptotic effect in both experimental and clinical studies, and sorafenib is the only approved drug for the systemic treatment of HCC. Thus, this study was designed to investigate the combined effect of melatonin and sorafenib on proliferation, apoptosis, and its possible mechanism in human HCC. Here, we found that both melatonin and sorafenib resulted in a dose‐dependent growth inhibition of HuH‐7 cells after 48 hours treatment, and the combination of them enhanced the growth inhibition in a synergistic manner. Colony formation assay indicated that co‐treatment of HuH‐7 cells with melatonin and sorafenib significantly decreased the clonogenicity compared to the treatment with single agent. Furthermore, FACS and TUNEL assay confirmed that melatonin synergistically augmented the sorafenib‐induced apoptosis after 48 hours incubation, which was in accordance with the activation of caspase‐3 and the JNK/c‐jun pathway. Inhibition of JNK/c‐jun pathway with its inhibitor SP600125 reversed the phosphorylation of c‐jun and the activation of caspase‐3 induced by co‐treatment of HuH‐7 cells with melatonin and sorafenib in a dose‐dependent manner. Furthermore, SP600125 exhibited protective effect against apoptosis induced by the combination of melatonin and sorafenib. This study demonstrates that melatonin in combination with sorafenib synergistically inhibits proliferation and induces apoptosis in human HCC cells; therefore, supplementation of sorafenib with melatonin may serve as a potential therapeutic choice for advanced HCC.     

A Novel Method for Three-Dimensional Analysis of Endoscopic Spatial Relationships of Pterygopalatine Fossa Structures and Associated Regions

Background: The spatial orientation rules of the important skull base structures are essential for performing endoscopic surgery. However, there is no satisfactory three-dimensional (3-D) anatomy study available to the surgeon at present. The aims of this study are to construct a new method to learn the spatial orientation of anatomical features under endoscopy and to help the surgeon establish a 3-D image of skull base structures in his mind. Methods: A modified MicronTracker navigation system was used to measure the pitch angle, direction angle and distance from the reference points to various anatomical landmarks of the pterygopalatine fossa and related structures (PPFRS) at the skull base in 10 fresh cadavers (20 sides). Results: The location data of the positions of the major landmarks were acquired and a digital model of the anatomical structures of the PPFRS was built, which can be moved, whirled or demonstrated easily. Conclusion: It is practical to measure the positions of the anatomical structures of the PPFRS with a modified binocular vision-based MicronTracker navigation system. It is a valuable exploration tool to help the surgeon establish the orientation of surgical landmarks in his mind by the 3-D parameters and model.     

Comparative Evaluation of Two Hemagglutinating Encephalomyelitis Coronavirus Vaccine Candidates in Mice

Porcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.