Characteristics of High Risk People with Cardiovascular Disease in Chinese Rural Areas: Clinical Indictors, Disease Patterns and Drug Treatment

Background and Aims: Current cardiovascular disease (CVD) prevention is based on diagnosis and treatment of specific disease. Little is known for high risk people with CVD at the community level. In rural China, health records of all residents were established after the recent health reforms. This study aims to describe the characters of the rural population with high CVD risk regarding their clinical indicators, disease patterns, drug treatment and adherence. Methods and Results: 17042 (87%) of all the 19500 rural residents in the two townships had valid health records in 2009. We employed a validated tool, the Asian Equation, to screen 8182 (48%) resident health records of those aged between 40-75 years in 2010. Those who were identified with a CVD risk of 20% or higher were selected for a face-to-face questionnaire survey regarding their diagnosed disease and drug treatment. 453 individuals were identified as high risk of CVD, with an average age of 53 years, 62% males, 50% smoking rate and average systolic blood pressure of 161 mmHg. 386 (85%) participated in the survey, while 294 (76%) were diagnosed with and 88 (23%) were suspects of CVD, hypertension, diabetes or hyperlipidaemia. 75 (19%) took drug regularly and 125 (32%) either stopped treatment or missed drugs. The most often used drugs were calcium channel blockers (20%). Only 2% used aspirins and 0.8% used statins. The median costs of drugs were 17 RMB (USD2.66) per month. Conclusion: The majority of the high risk population in our setting of rural China had already been diagnosed with a CVD related disease, but very few took any drugs, and less still took highly effective drugs to prevent CVD. A holistic strategy focused on population with high risk CVD and based on the current China public health reform is suggested in the context of primary care. © 2013 Wei et al.published_or_final_versio

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model. Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 mu g) within the limited administration volume (10 mu L) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.Peer reviewe

Virtual Inertia Coordinated Allocation Method Considering Inertia Demand and Wind Turbine Inertia Response Capability

Wind turbines can have inertia characteristics similar to synchronous generators through virtual inertia control, which helps to provide the inertia support for the system. However, there is the problem of how to coordinate the allocation of virtual inertia among wind turbines. In response to this problem, this paper first analyzes the inertia response capabilities of wind turbines and puts forward an evaluation index that quantifies the inertia response capability of wind turbines. The inertia response capability of a wind farm is evaluated at the entire system level. Based on the evaluation index, the virtual inertia coordinated allocation method considers the system inertia demand and the inertia response capabilities of the wind turbines. It is proposed to release the inertia response capability of each wind turbine while avoiding an excessive release of kinetic energy and bring a second impact by wind turbines’ exiting operation. Finally, the effectiveness of the proposed method is verified by a simulation case study

Identification and characterization of TOR in Macrobrachium rosenbergii and its role in muscle protein and lipid production

Abstract The recent scarcity of fishmeal and other resources means that studies on the intrinsic mechanisms of nutrients in the growth and development of aquatic animals at the molecular level have received widespread attention. The target of rapamycin (TOR) pathway has been reported to receive signals from nutrients and environmental stresses, and regulates cellular anabolism and catabolism to achieve precise regulation of cell growth and physiological activities. In this study, we cloned and characterized the full-length cDNA sequence of the TOR gene of Macrobrachium rosenbergii (MrTOR). MrTOR was expressed in all tissues, with higher expression in heart and muscle tissues. In situ hybridization also indicated that MrTOR was expressed in muscle, mainly around the nucleus. RNA interference decreased the expression levels of MrTOR and downstream protein synthesis-related genes (S6K, eIF4E, and eIF4B) (P < 0.05) and the expression and enzyme activity of the lipid synthesis-related enzyme, fatty acid synthase (FAS), and increased enzyme activity of the lipolysis-related enzyme, lipase (LPS). In addition, amino acid injection significantly increased the transcript levels of MrTOR and downstream related genes (S6K, eIF4E, eIF4B, and FAS), as well as triglyceride and total cholesterol tissue levels and FAS activity. Starvation significantly increased transcript levels and enzyme activities of adenylate-activated protein kinase and LPS and decreased transcript levels and enzyme activities of FAS, as well as transcript levels of MrTOR and its downstream genes (P < 0.05), whereas amino acid injection alleviated the starvation-induced decreases in transcript levels of these genes. These results suggested that arginine and leucine activated the TOR signaling pathway, promoted protein and lipid syntheses, and alleviated the pathway changes induced by starvation

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

Abstract Background MYO15A variants are responsible for human non-syndromic autosomal recessive deafness (DFNB3). The majority of MYO15A variants are associated with a congenital severe-to-profound hearing loss phenotype, except for MYO15A variants in exon 2, which cause a milder auditory phenotype, suggesting a genotype-phenotype correlation of MYO15A. However, MYO15A variants not in exon 2 related to a milder phenotype have also been reported, indicating that the genotype-phenotype correlation of MYO15A is complicated. This study aimed to provide more cases of MYO15A variation with diverse phenotypes to analyse this complex correlation. Methods Fifteen Chinese autosomal recessive non-syndromic hearing loss (ARNSHL) individuals with MYO15A variants (8 males and 7 females) from 14 unrelated families, identified by targeted gene capture of 127 known candidate deafness genes, were recruited. Additionally, we conducted a review of the literature to further analyses all reported MYO15A genotype-phenotype relationships worldwide. Results We identified 16 novel variants and 12 reported pathogenic MYO15A variants in 15 patients, two of which presented with a milder phenotype. Interestingly, one of these cases carried two reported pathogenic variants in exon 2, while the other carried two novel variants not in exon 2. Based on our literature review, MYO15A genotype-phenotype correlation analysis showed that almost all domains were reported to be correlated with a milder phenotype. However, variants in the N-terminal domain were more likely to cause a milder phenotype. Using next-generation sequencing (NGS), we also found that the number of known MYO15A variants with milder phenotypes in Southeast Asia has increased in recent years. Conclusion Our work extended the MYO15A variant spectrum, enriched our knowledge of auditory phenotypes, and tried to explore the genotype-phenotype correlation in different populations in order to investigate the cause of the complex MYO15A genotype-phenotype correlation

Polarized Micro-Raman Spectroscopy and 2D Convolutional Neural Network Applied to Structural Analysis and Discrimination of Breast Cancer

Raman spectroscopy has been efficiently used to recognize breast cancer tissue by detecting the characteristic changes in tissue composition in cancerization. In addition to chemical composition, the change in bio-structure may be easily obtained via polarized micro-Raman spectroscopy, aiding in identifying the cancerization process and diagnosis. In this study, a polarized Raman spectral technique is employed to obtain rich structural features and, combined with deep learning technology, to achieve discrimination of breast cancer tissue. The results reconfirm that the orientation of collagen fibers changes from parallel to vertical during breast cancerization, and there are significant structural differences between cancerous and normal tissues, which is consistent with previous reports. Optical anisotropy of collagen fibers weakens in cancer tissue, which is closely related with the tumor’s progression. To distinguish breast cancer tissue, a discrimination model is established based on a two-dimensional convolutional neural network (2D-CNN), where the input is a matrix containing the Raman spectra acquired at a set of linear polarization angles varying from 0° to 360°. As a result, an average discrimination accuracy of 96.01% for test samples is achieved, better than that of the KNN classifier and 1D-CNN that are based on non-polarized Raman spectra. This study implies that polarized Raman spectroscopy combined with 2D-CNN can effectively detect changes in the structure and components of tissues, innovatively improving the identification and automatic diagnosis of breast cancer with label-free probing and analysis

Phenotype prediction of Mohr-Tranebjaerg syndrome (MTS) by genetic analysis and initial auditory neuropathy

Abstract Background Mohr-Tranebjaerg syndrome (MTS) is a rare X-linked recessive neurodegenerative disorder resulting in early-onset hearing impairment, gradual dystonia and optic atrophy. MTS is caused by variations in the nuclear TIMM8A gene, which is involved in mitochondrial transport of metabolites. This study aimed to identify the pathogenic gene variations in three Chinese families associated with predicted MTS with or without X-linked agammaglobulinaemia. Methods Otologic examinations, vestibular, neurological, optical and other clinical evaluations were conducted on the family members. Targeted genes capture combining next generation sequencing (NGS) was performed, and then Sanger sequencing was used to confirm the causative variation. Results A novel variation, c.232_233insCAAT, in TIMM8A was identified as the pathogenic variation in one Chinese family. This variation co-segregated with the most frequent phenotypic deafness and was absent in the 1000 Genomes Project, ExAC and 1751 ethnicity-matched controls. Clinically, otological examinations illustrated the typical postsynaptic auditory neuropathy for the proband without the symptoms of dystonia or optic atrophy. MRI demonstrated abnormal small cochlear symmetric nerves, while the vestibular function appeared to be less influenced. Furthermore, we found another two TIMM8A variations, the deletion c.133_135delGAG and a copy number variation (CNV) including the TIMM8A gene, in two independent case, when we performed NGS on an auditory neuropathy population. Conclusion We identified two novel variations in the TIMM8A gene (c.232_233insCAAT and c.133_135delGAG) and a CNV including the TIMM8A gene in three independent Chinese families with predicted MTS. To our knowledge, this is the first report of TIMM8A variations being identified in a Chinese population. Our results enrich the variation spectrum of TIMM8A and clinical heterogeneity of MTS. Genetic detection and diagnosis is a powerful tool for better understanding and managing syndromic hearing impairments, such as MTS, before they become full-blown

Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model

Destruction of extracellular matrix (ECM) is one of the basic steps of tumor invasion and metastasis. Matrix metalloproteinase (MMP) 9, a kind of zinc-ion-dependent endopeptidase, can degrade almost all protein components in the ECM, destroy the histological barrier of tumor cell invasion, and play a key role in tumor invasion and metastasis. The role of MMP-9 in tumor invasion and metastasis has attracted increasing attention and is considered the main proteolytic enzyme in this process. Although the overexpression of MMP-9 was detected in Oral squamous cell carcinoma (OSCC) tissues, further basic studies in vivo and in vitro are needed to investigate the role of MMP-9 in OSCCs and provide scientific validation. In this research, we developed a novel OSCC zebrafish xenograft model to study the role of the MMP-9 gene in oral carcinogenesis. Firstly, the MMP-9/shRNA lentiviral clone and control virus were constructed and transfected into OSCC cells. Then, the decreasing expression of MMP-9 was verified by RT-PCR and immunocytochemistry. Cell proliferation was detected by MTT assay. Colony formation was evaluated by colony formation assay. Cell invasion was evaluated using transwell invasion assay in vitro. In addition, OSCC cells with MMP-9/shRNA knockdown and control vector were injected into zebrafish and an OSCC tumor model in zebrafish was established to evaluate invasion and metastasis in vivo. Knockdown of MMP-9 gene by shRNA could inhibit OSCC cell growth and clone formation and markedly suppress cell invasion in vitro. And the knockdown of the MMP-9 gene could also significantly decrease the metastatic distance and number of metastatic tumor cells or lesions in vivo and suppress the metastasis rate in xenografted zebrafish. Taken together, these evidences indicated that the knockdown of MMP-9 might suppress OSCC cell invasion and metastasis in vivo and in vitro. The MMP-9 gene may be a promising therapeutic target for OSCCs in the future

Assessing mechanisms for microbial taxa and community dynamics using process models.

Disentangling the assembly mechanisms controlling community composition, structure, distribution, functions, and dynamics is a central issue in ecology. Although various approaches have been proposed to examine community assembly mechanisms, quantitative characterization is challenging, particularly in microbial ecology. Here, we present a novel approach for quantitatively delineating community assembly mechanisms by combining the consumer-resource model with a neutral model in stochastic differential equations. Using time-series data from anaerobic bioreactors that target microbial 16S rRNA genes, we tested the applicability of three ecological models: the consumer-resource model, the neutral model, and the combined model. Our results revealed that model performances varied substantially as a function of population abundance and/or process conditions. The combined model performed best for abundant taxa in the treatment bioreactors where process conditions were manipulated. In contrast, the neutral model showed the best performance for rare taxa. Our analysis further indicated that immigration rates decreased with taxa abundance and competitions between taxa were strongly correlated with phylogeny, but within a certain phylogenetic distance only. The determinism underlying taxa and community dynamics were quantitatively assessed, showing greater determinism in the treatment bioreactors that aligned with the subsequent abnormal system functioning. Given its mechanistic basis, the framework developed here is expected to be potentially applicable beyond microbial ecology

Two Novel Sesquiterpenoid Glycosides from the Rhizomes of <i>Atractylodes lancea</i>

Secoatractylohexone A (1), an unprecedented secoguaiane lactone glycoside featuring 6/7 cores and dihydroxy-9-guaine-3-one 11-O-β-d-glucopyranoside (2), a 9,10-unsaturated guaiene-type glycoside possessing an uncommon scaffold, were isolated from the water-soluble portion of the ethanolic extract of Atractylodes lancea rhizomes together with five known compounds (3–7). The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic data and application of the CD technique. The potential biological activities of secoatractylohexone A were predicted by network pharmacology in silico, the result of which indicated that secoatractylohexone A may be used to treat type II diabetes