ABSTRACT
Intervertebral disc degeneration (IDD) refers to the biomechanical and structural changes of intervertebral disc tissues due to the effects of a variety of factors. Theses physical or chemical factors lead to the rupture of the annulus fibrous, protrusion of the nucleus pulposus tissue, compression of the spinal cord and nerve roots and causing the patient's back and leg pain ultimately. Degeneration of intervertebral disc is a common condition in clinical practice, which affects working ability and daily living quality of patients seriously. Due to the change of living habits, the population with IDD tend to be younger recently. The etiology, pathogenesis and diagnosis and interventions of IDD have always been hot topics in spinal surgery. Thus, animal models of IDD close to the human body has a of great clinical significance for exploring the etiology, pathological mechanism and non-surgical treatment of IDD. At present, the establishment of IDD model mainly includes two following aspects, in vitro model and in vivo model. There are two main in vitro models, cell culture and tissue or organ culture. There are seven kinds of in vivo models, which can be divided into two categories, namely spontaneous and induced model. Among them, the spontaneous degeneration model is also regarded as age-related degeneration, while the induced model refers to the construction of the animal model of IDD by injuring the structure of the intervertebral disc, changing the biomechanical structure of the vertebral body, development spinal instability caused by surgery or constructing nerve root compression and gene knockout. Although there are many methods of animal modeling and literature reports, each method has its own advantages and disadvantages. The advantages and disadvantages should be weighed when choosing the animal models.
ABSTRACT
Low back pain is becoming an important factor affecting people's quality of life, while the age of its onset is getting younger and younger, and the social and economic losses caused by low back pain are huge every year. Intervertebral disc degeneration (IDD) is an important cause of low back pain. Due to multiple factors, biomechanical and structural changes occur in intervertebral disc tissue, including rupture of annulus fibrosus, protrusion of nucleus pulposus, which cause compression of spinal cord and nerve root, and lower back pain. Micro-RNA (miRNA) is a kind of single-stranded non-coding small molecule RNA, with 18-24 nucleotides in length, which exists widely in eukaryotes. As one of the important regulatory molecules of gene expression, it has been proved to play a key role in the initiation and progression of many diseases, and it may also play an important role in intervertebral disc degeneration. At present, the clinical treatment for IDD is mainly surgical treatment to alleviate clinical symptoms. Even if surgical treatment can achieve good results, it will bring great physical trauma and economic burden to patients. The role of miRNA in IDD is one of the hotspots in the current academic research. Studies have shown that miRNA has abnormal expression patterns in degenerative intervertebral disc tissues and participates in a variety of pathological processes of IDD. At present, some miRNAs have been proved to be related to a variety of pathological processes in IDD, including nucleus pulposus cell apoptosis and proliferation, extracellular matrix degradation, autophagy, inflammation and cartilage endplate degeneration. The comparative study of gene chip showed that there were significant differences in the expression of some miRNAs between degenerative and normal nucleus pulposus cells. These differentially expressed miRNAs may be involved in the process of nucleus pulposus cell degeneration by regulating their respective upstream or downstream pathways. Most of the regulatory pathways are crossed and parallel, thus constructing a huge miRNA regulatory network. Understanding the target genes and mechanisms of miRNA in the pathogenic process can provide an important reference for the origin, development and prognosis of IDD. In this article, the important role of miRNA in IDD and the potential significance of clinical treatment are reviewed. With the in-depth study of miRNA and the molecular biological mechanism can provide new ideas for the diagnosis and treatment of IDD, which is likely to become a new strategy for biological treatment of IDD.
ABSTRACT
Objective:Resorption can occur after lumbar disc herniation, and Thymic stromal lymphopoietin (TSLP) is considered to be a key factor mediating reabsorption. Studies have found that under the action of inflammatory factors like TNF-α, IL-6, etc,the expression of TSLP in intervertebral disc tissue was increased, and then mononuclear macrophage chemokine-1 (MCP-1) was induced to induce infiltration of macrophage to promote reabsorption. To determine the mechanism, we design the experiment to explore the mechanism of IL-6-mediated JAK/STAT pathway and TGF-β/Smad pathway to promote the reabsorption of intervertebral disc by regulating the expression of TSLP.Methods:Rat bone marrow mesenchymal stem cells (MSC) and rat nucleus pulposus cells (NPC) were cultured in vitro, treating the cells withrat IL-6 recombinant protein, STAT3inhibitor and Smad2/3 inhibitorrespectively, and use real-time quantitative PCR (qRT-PCR) technology to detect the expression of JAK1, STAT3, Smad2, TSLP mRNA under different conditions; Western blot to detect the expression of TSLP, Smad2 and phosphate STAT3 protein; using enzyme-linked immunosorbent assay (Elisa) to detect the expression of TGF-β in two rat cells under the treatment of IL-6.Results:After stimulation ofIL-6 (10 ng/ml or 100 ng/ml) the expression of JAK1in MSC (10 ng/ml: 5.13±1.21; 100 ng/ml: 5.23±0.35; control group: 0.97±0.03), STAT3 (10 ng/ml: 6.50±0.38; 100 ng/ml: 6.74±0.61; control group: 0.87±0.19) was significantly increased, and TSLP also showed high expression in MSC (10 ng/ml: 4.26±0.38; 100 ng/ml: 5.05±0.46; control group: 1.04±0.04).The expression of STAT3 (10 ng/ml: 2.91±0.08; control group: 1.12±0.11), TSLP (10 ng/ml: 7.32±0.37; control group: 1.03±0.03) in NPC also increased. After stimulation of IL-6, the expression of Smad2 increasing in MSC was observed (10 ng/ml: 15.92±0.62; 100 ng/ml: 20.28±0.58; control group: 0.96±0.08), and increased expression of Smad2 in NPC (10 ng/ml: 5.01±0.17; control group: 0.96±0.03). The expression of TSLP in MSC decreased after adding STAT3 inhibitor (BP group, BP group: 0.17±0.01; control group: 0.90±0.09), the expression of TSLP also decreased in NPC (BP group: 0.42±0.11; control group: 0.90±0.11). After adding Smad2/3 inhibitor (SB group), the expression of TSLP in MSC decreased (SB group: 0.33±0.01; control group: 1.02±0.02), and the expression of TSLP in NPC also decreased (SB group: 0.40±0.04; control group: 0.99±0.01).Conclusion:IL-6 up-regulates TSLP expression via the JAK1/STAT3 signaling pathway and promotes prominent intervertebral disc reabsorption. At the same time, IL-6 can activate the TGF-β/Smad2/3 pathway and up-regulate the expression of TSLP, which play a synergistic role in the reabsorption process.
ABSTRACT
Low back pain is becoming an important factor that affects people's quality of life today, and the social losses caused by lowback pain are hugeevery year. Lumbar disc herniation (LDH) is one of the main diseases that cause low back pain. The mechanism of lumbar disc herniation in the biomedical science is still controversial. Inflammatory factor is a cytokine secreted by tissue cells and involved in mediating the inflammatory response. Studies have shown that some factors stimulated by the extrusive nucleus pulposus, like inflammatory factors, degeneration-related genes and downstream expression products, can cause the degeneration of intervertebral disc. IL-1, IL-6, TNF-α, MMPs, and TGF-β have become the hot topicin disc degeneration. Signaling pathway is the main pathway for inflammatory factors to participate in the regulation of various biochemical reactions in cells. The inflammatory factors interact with different proteins to activate or inhibit different pathways, thereby achieving regulation of the cell cycle, regulates gene expression, induces immune inflammatory response, and apoptosis. Research on the role of various inflammatory factors in the body and related molecular signaling pathways will help us understand the mechanism of LDH. Most of the experimental studies only focus on the influence of a certain cytokine or single pathway on intervertebral disc degeneration, but different inflammatory factors and their signaling pathways often crosstalk with each other through special channels, forming a complex and precise signal transduction regulation network jointly regulates various physiological or pathological processes in the body, and the occurrence of disease is often accompanied by multiple factors. Studying the effect of a single signal network on the disease cannot fully explain the cause of the disease and related clinical manifestations. Therefore, clarifying the role of various inflammatory factors in IDD and exploring and analyzing the ways in which each factor regulates each other will provide ideas for understanding the mechanism of lumbar degeneration and exploring new methods for preventing and treating LDH in the future.
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Objective To investigate the feasibility of the automatic cystocele severity grading software for quantitative evaluation of prolapse of bladder posterior wall by transperineal ultrasound . Methods One hundred and seventy transperineal ultrasound video clips were recorded when the female patients performing the Valsalva maneuver and those clips were divided into training group ( 85 cases) and test group ( 85 cases) randomly ,then the ralated structures of the images from the training group offline were marked . Through machine learning algorithm ,the computer had learned and was able to analyzed the marking information ,then the automatic cystocele severity grading software was obtained . And later the software was ran to mark the structures and get the cystocele severity grading in the images from the test group . Meanwhile , the same structures of the same images manually were marked and after an interval of more than two weeks the process were repeated by 3 doctors . Finally the grading results obtained from the software and the measurers of the 3 doctors were compared . Results The intelligent identification and automatic measurement software obtained from the machine learning algorithm was able to identify the related structures . The grading results of each measurer were of good consistency ( κ :0 .72 －0 .78 ;ICC :0 .980－0 .990) . The grading results between different measurers were of good consistency ( κ :0 .65－0 .75 ;ICC :0 .985－0 .992) . The grading results between automatic software and three different measurers were of good consistency ( κ :0 .63－0 .67 ;ICC :0 .967－0 .969 ; r ＝0 .936 ,0 .943 ,0 .936 ,all P ＜0 .01) . Conclusions The automatic cystocele severity grading software is able to identify the related structures in the images and reliable to apply the software in pelvic floor ultrasound .
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Objective To explore the application value of invasive intracranial pressure (ICP) monitoring in children with severe traumatic brain injur (sTBI).Methods A total of 158 children with sTBI in our hospital from January 2012 to March 2015 were collected and retrospectively analysed.According to whether the child recieved invasive ICP monitoring or not,they were divided into the monitoring group (80 cases) and the control group (78 cases).Children in the monitoring group were embed of invasive ICP monitoring device within first 24 h after surgery,and were treated with appropriate measures according to the ICP level.In the control group,the determination of whether needing to recieve head CT and adjusting the treatment program was made based on the clinical symptoms and surgeon′s experiences.The prognosis of children in the two groups were evaluated by Glasgow coma scale (GOS) and compared at 3 months after injury.At the same time,the prognosis of children in the monitoring group with different ICP levels were compared.Results The favorable prognosis rates in the monitoring group and control group were 61.2% and 41.0% respectively,and there was statistically significant difference between the two groups(P<0.05).The mortality rates of children in the monitoring group had statistical difference among different ICP levels(P<0.05).Conclusion For children with sTBI,the invasive ICP monitoring is contribute to dynamically observing the changes in ICP,early detecting changes of conditions,guiding clinical treatment,and improving the prognosis.
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Objective To investigate the effect of health literacy on stroke education in patients with ischemic cerebrovascular disease and their family members.Methods Health literacy questionnaire was used to conduct the health literacy questionnaire survey for patients with ischemic cerebrovascular disease and their family members.The respondents received stroke education randomly through neurologists' explanation or self-reading.The corresponding questionnaire was used to evaluate the mastering of the content of stroke education for the respondents.Results The complete data of 42 patients with ischemic cerebrovascular disease (34 ischemic stroke and 8 transient ischemic attack) and 57 family members of the patients with ischemic cerebrovascular disease were collected and enrolled in the analysis.The good health literacy score group (＜ 10) and the poor health literacy score group (≥ 10) were 61 and 38 subjects respectively.The proportions of younger age (x2 =16.410,P ＜0.001) and high school or above (68.85％ vs.23.68％ ;x2 =19.25,P ＜ 0.001) of the former were higher than those of the latter,and the proportion of patients (32.79％vs.57.89％;x2 =6.043,P=0.014) was significantly lower than that of the latter,but there was no significant difference in the proportion of the males between the two groups (55.74％ vs.44.74％ ;x2 =1.134,P =0.287).Multivariate logistic regression analysis showed that health literacy was independently associated with the age of respondents (≤40 years:odds ratio [OR] 7.753,95％ confidence interval [CI]1.208-49.740; P=0.031) and the level of education (high school and above:OR,3.993,95％ CI 1.305-12.218; P=0.015),and it was not correlated with gender and role.Those with good stroke education score (≥7)and poor stroke education score (＜7) were 57 and 42,respectively.The proportions of younger age (x2 =17.095,P ＜0.001),high school and above (70.00％ vs.23.08％ ;x2 =20.836,P ＜ 0.001),and good health literacy score (88.33％ vs.20.51％;x2 =45.968,P＜0.001) were significantly higher than those of the latter,while there were no significant differences in the proportions of gender,role,and stroke education.Multivariatelogistic regression analysis showed that only the good health literacy was independently associated with the stroke education score (OR 20.147,95％ CI6.089-66.655; P＜0.001).Conclusions Health literacy can significantly affected the effect of the stroke education in patients with ischemic cerebrovascular disease and their family members.In the development of individualized stroke education program,it should be considered.