Non clinical pharmacodynamic evaluation system of high-altitude hypoxic brain injury / 药学学报

The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.

Evaluation of non-clinical anxiety disorder models / 药学学报

Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.

Three-dimensional cone beam computed tomography analysis of temporomandibular joint response to the Twin-block functional appliance / 대한치과교정학회지

OBJECTIVE@#To propose a three-dimensional (3D) method for evaluating temporomandibular joint (TMJ) changes during Twin-block treatment.@*METHODS@#Seventeen patients with Class II division 1 malocclusion treated using Twin-block and nine untreated patients with a similar malocclusion were included in this research. We collected their cone beam computed tomography (CBCT) data from before and 8 months after treatment. Segmentations were constructed using ITK-SNAP. Condylar volume and superficial area were measured using 3D Slicer. The 3D landmarks were identified on CBCT images by using Dolphin software to assess the condylar positional relationship. 3D models of the mandible and glenoid fossa of the patients were constructed and registered via voxel-based superimposition using 3D Slicer. Thereafter, skeletal changes could be visualized using 3DMeshMetric in any direction of the superimposition on a color-coded map. All the superimpositions were measured using the same scale on the distance color-coded map, in which red color represents overgrowth and blue color represents resorption.@*RESULTS@#Significant differences were observed in condylar volume, superficial area, and condylar position in both groups after 8 months. Compared with the control group (CG), the Twin-block group exhibited more obvious condyle-fossa modifications and joint positional changes. Moreover, on the color-coded map, more obvious condyle-fossa modifications could be observed in the posterior and superior directions in the Twin-block group than in the CG.@*CONCLUSIONS@#We successfully established a 3D method for measuring and evaluating TMJ changes caused by Twin-block treatment. The treatment produced a larger condylar size and caused condylar positional changes.

Exploration of nonclinical pharmacodynamics evaluation system of Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.

Exploration of non-clinical pharmacodynamics evaluation system of amyotrophic lateral sclerosis / 药学学报

Amyotrophic lateral sclerosis (ALS) is among the most common type of motor neuron diseases, and its pathogenesis remains unclear. In recent years, our understanding of the genetic basis of ALS has led to the development of various ALS disease models, which allow for screening of ALS-related drugs and treatment methods. This review focuses on the research progress of ALS, summarizes the systems of commonly used experimental animal models, including transgenic animals, gene knockout approaches and autonomous animal models, points to the problems needing attention in standardized ALS non-clinical research, and proposes the criteria for selection of standardized R&D model.

Role of Nrf2 in neurodegenerative diseases and recent progress of its activators / 药学学报

The nuclear factor erythroid 2 related factor 2 (Nrf2) is a key protein of endogenous antioxidant defense systems in the body. In response to oxidative stress, Nrf2 translocates to nucleus and binds to antioxidant response elements (ARE), regulating the expression of a large amounts of antioxidant genes and maintaining a proper redox balance. The pathological processes of neurodegenerative diseases are associated with generation of reactive oxygen species, which cause oxidative stress. Oxidative stress plays a cardinal role in the onset and progression of neurodegenerative diseases. Nrf2-inducer compounds can reduce oxidant stress and have shown therapeutic efficacy in many neurodegenerative disease models. How to activate the Nrf2 signaling pathway effectively has been received much attention. Here we provided an overview of specific mechanism of Nrf2-ARE pathway and the protective effects of Nrf2 in different neurodegenerative diseases, and summarized the Nrf2 activators recently in preclinical study.

Role of DNA-associated autoantibodies to cell membrane in the diagnosis of juvenile systemic lupus erythematosus / 中华儿科杂志

<p><b>OBJECTIVE</b>To establish a method of indirect immunofluorescence (IIF) to measure DNA (mDNA)-associated autoantibodies to cell membrane, and to evaluate diagnostic value of the anti-mDNA antibodies in patients with juvenile systemic lupus erythematosus (SLE) in comparison with anti-dsDNA antibody.</p><p><b>METHODS</b>Forty-four children with SLE were enrolled in this study. As a control group, 30 children with other rheumatic diseases were also enrolled. Anti-mDNA and anti-dsDNA antibodies were measured by IIF. Anti-smooth muscle (Sm) antibodies were measured by immuno-double diffusion (ID) and IIF.</p><p><b>RESULTS</b>Out of 44 juvenile SLE patients, 34 (77.27%) were seropositive for anti-mDNA, which was significantly higher than that of patients with other rheumatic diseases (20.00%, P<0.05). The sensitivity and specificity of anti-mDNA for juvenile SLE diagnosis were 77.27% and 80.00%, respectively. The positive predictive value and negative predictive value were 85.00% and 70.59%, respectively. The positive rate of anti-mDNA in SLE lacking of anti-dsDNA and anti-Sm antibodies were 68.00% (17/25) and 79.49% (31/39), respectively.</p><p><b>CONCLUSION</b>The detection of anti-mDNA antibodies is useful for diagnosis of juvenile SLE, especially in patients who are negative for anti-dsDNA antibodies and anti-Sm antibodies.</p>

Studies on chemical constituents from leaves of Sapium sebiferum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from leaves of Sapium sebiferum.</p><p><b>METHOD</b>The compounds were isolated and purified by silic gel column chromatography and preparative HPLC. The structures were identified by various spectral evidence.</p><p><b>RESULT</b>Nine compounds were obtained and they were shikimic acid (1), kaempferol (2), quercetin (3), isoquercein (4), hyperin (5), kaempferol-3-O-beta-D-glucopyranoside (6), kaempferol-3-O-beta-D-glueopyranoside (7), gallic acid (8), rutin (9).</p><p><b>CONCLUSION</b>Compounds 1, 5, 6 and 7 are isolated from this genus for the first time and compound 9 is isolated from this plant for the first time.</p>