| With the improvement of people's living conditions and increasing length of life rapidly, people in the world now are having longer life, there are more and more elderly people in the present society. Joint disease is mainly the threatening factor to human's health, especially to elder people. Therefore, it has attracted more and more attention for the research issue in medicine. The earlier diagnosis, treatment and prognosis on joint diseases is an important project for researchers working in medicine. Generally, the joint diseases develop slowly and unexpectedly, so that when the diagnosis is made it is critical. If it is engaged in the medium or late stage, the optimal time for treatment will be missed. Nevertheless, at the present, some checking for taking complete examination are focused on manifestations and sign, physical check, X-ray and magnetic resonance imaging (MRI) of joint cartilage, etc. There remain some shortages in the field of making the earlier diagnosis on it. So, if we can develop a kind of synovial fluid analysis technique with high sensitivity and specificity which can reflect the pathological change of joint and estimate its prognosis rapidly in the earlier stage of joint diseases. It will be of great significance not only in the earlier diagnosis but also in the course of estimating its prognosis. Therefore, we employed the techniques of quasi-elastic laser light scattering, multi-dimensional microscopy and image analyzing, and phase analysis electrophoresis laser-scattering to systematically research the physical and chemical properties of synovial fluid, like the structure and size distribution of the micro-particles, the size and size distribution of the nano-particles, as well as their surface charge, as functions of the types, the stage and the treatment of joint diseases. At the same time, we also performed measurements on the absorbing spectrum, SDS-PAGE electrophoresis, pH value and viscosity of the synovial fluid. By analyzing the experimental results and the correlative mechanism among the parameters, some conclusions have been made as follows:(1) The shape and size of micro-particles (average diameter more than 1μm) are related with normal or exceptional state of arthrosis. The diameter of the particles in normal synovial fluid is smaller, and the shape of them are mostly small and circular, the range of the size distribution is very narrow, elongation less, the roundness factor, compactness and the integrated density per 10000 μm2 larger. The diameter of the particles in knee osteoteoarthritis (KOA) synovial fluid is larger, of which the amount of strip-shaped or claviform increases, the elongation becomes larger and the roundness factor, compactness and the integrated density per 10000 μm2 are decreased, and the range of size distribution is broader than the one of normal synovial fluid. The average diameter of particles in knee traumatic synovitis (KTS) synovial fluid is largest, the range of the size distribution is much more broad than normal and KOA synovial fluid, the elongation larger, the roundness factor, density and the integrated density per 10000 μm2 decrease, and more strip-shaped or claviform particles are observed. With deterioration of the severity of the disease, the size of the micro-particles in synovial fluid gradually enlarges, the elongation gradually increases, and the roundness factor gradually decreases, the compactness and average integrated density per 10000 μm2 gradually decreases, particles change from small and dumpy roundness shape approximately to large and long or clubbed shape. In different therapy periods, the shape, size and its distribution of synovial fluid particles also change. In the early stage of KOA, after it was treated for two periods, the shape and size of synovial fluid particles decrease to normal level. For the KOA in middle and late stage and KTS patients, by treating for two periods, the size of synovial fluid particles decrease obviously. However, compared with normal level, there are still some gaps exist. Therefore, the analysis and measurement of micro-particles of synovial fluid can be as a useful and exact criterion for estimating the degree of arthropathy and prognosis.(2) Among various of arthropathys, the average diameter and the size distribution ofnano-particles (diameter less than 1μm) in synovial fluid is related to the types of arthropathy, the degree and the repair degree of arthrosis injury after dosing to patients, meanwhile, they response to the disease more quickly. For different arthropathys, the average diameters of the nano-particle in synovial fluid are different obviously, and there is greatly difference for the average diameter of particle in synovial fluid in different periods of arthropathys as well as pre and past-treating. Consequently, the average diameter of the nano-particles in synovial fluid can reflect accurately and rapidly the injury degree and the repair degree of arthrosis. It is expected that a kind of inspecting approach can be built on early diagnose, treatment and prognosis of arthropathys according to this method, combined with clinical treatment experience.(3) The forming mechanisms of the micro-particles and nano-particles in synovial fluid and arthropathys are as follows: after injury of arthrosis, the protein content increases, thus make the pH value of synovial fluid changes to deflected neutral from normal weak alkalescence, so that the surface charge density of nano-particles o decrease, this lead to more polymerization of the nano-particle, as a result, it brings forward some larger size and molecular weight of particles, at the same time, the viscidity of synovial fluid decreases and it is diluted gradually so as to decrease lubricate ability. Consequently, friction degree of arthrosis is aggravated to wear out particles, which lead to further developing of arthropathys.(4) There are different for cytokines concentration in synovial fluid between normal people and KOA patients. For normal people, the concentrations of TNF-α and IL-6 are lower obviously than KOA patients, and there is linear relationship between the concentrations of TNF-α and IL-6. The levels of TNF-α and IL-6 in synovial fluid are related to KOA degree, the worse KOA is, the higher concentrations of TNF-α and IL-6. In the blood serum of KOA patients, the concentrations of TNF-α and IL-6 increase with increasing degree of KOA. Although the level of the cell factorsin synovial fluid are higher than those in the serum of KOA patients, the level of TNF-α and IL-6 can reflect the cytokines level in synovial fluid, and represent decompose and destroy process of cartilage in knee joints.(5) By analyzing physical and chemical property of the synovial fluid correlatively with clinical diagnosis, we discovered that there is close correlation among the volume of tangible particles and intangible micro-particle, their Zeta potential, the severity extent of knee osteoarthritis and the evaluation of concrescence. By measuring these parameters we can judge the existence of KOA, the serious extent of KOA, the therapeutic efficacy and the evaluation of concrescence. The physical and chemical properties of synovial fluid micro-particles and nano-particles are correlated with the clinical scale and reflect the severity of KOA and therapeutic efficacy, thus provide a simple method of early period observation, initiative treatment and random evaluation of therapeutic efficacy.The innovation of this paper lies in:(1) Based on our knowledge, this is the first time to perform systematical measurements on the shape, structure, volume and size distribution of synovial fluid particle as functions of the types, stage and treatment of joint disease, and reveals the relation between these parameters and the engendering and evolution of the disease. With following up test on the contact area of the synovial fluid particles during different courses of treatment, we can set up a fast, undisturbed , and efficient detecting method of early diagnosing, healing and after healing decision.(2) It is also the first time to perform measurements on the size and size distribution of nano-particles in synovial fluid as functions of the types, stage and treatment of joint disease, the correlation of these parameters and different kinds of Joint disease is revealed. A fast, undisturbed, and efficient detecting method of early diagnosing, healing and after healing decision is suggested to set up.(3) The surface charge of the nano-particles in synovial fluid is also investigated the first time as the functions of the joint disease's sorts and severity. It is proved that not only a fast, undisturbed, and potent method of early diagnosing , healing and after healing decision can be setup by using the parameter, but also we can provide another method of early diagnose and heal as well as an experimental evidence of revealing the mechanism of joint disease evolution.(4) It is the first time to employed so many advanced techniques such as the dynamic laser light scattering, multi-dimensional microscopy and image analyzing, and phase analysis electrophoresis laser-scattering to analyze so many parameters which include the shape, structure, size and size distribution, surface charge density, and the molecular weight of synovial fluid particle; and the pH value, the viscosity, the cell factors of the synovial fluid. Thus revealing the mechanism of the particles forming and developing, as well as the development of the joint disease, and offering a new approach to diagnose joint disease with the advantages of simplicity, low-cost, quick response, high sensitivity and accuracy.(5) We used firstly statistics correlative analysis to compare the physical and chemical characteristics of the micro-particles and the nano-particles in synovial fluid with the clinical conventional diagnostic method. We proved the close relativity between physical and chemical characteristics of the grain and particulate in synovial fluid determined by the ways of dynamic light laser scattering, multi-dimension microscopy and imaging technique, phase analysis electrophoresis laser-scattering technique and diagnostic conclusion made by conventional diagnoses method (such as: inquiring, X-ray scanning, MRI scanning, et al). These techniques offered a new simple, reliable, cheap and easily extensible approach to diagnose and therapy joint disease.Here we have performed a systemic study on synovial fluid taken from patients who suffered various joint diseases or different degrees of joint disease or pre and post therapy. In this study synovial fluid were qualitatively and quantitatively analyzed. It focuses on the information of the components, the physical and chemical characteristics of synovial fluid during the joint disease development. The results demonstrated that the physical and chemical characteristics of synovial fluid correlate with the development of various joint diseases, so that the mechanism of joint disease development is revealed. A new analysis method, which can diagnose early joint fluid rapidly with convenience, high sensitivity and accuracy are also established. Furthermore, this study enriched the knowledge of mechanism and rule of synovial fluid at various joint states. Therefore, this study presents a beneficial revelation to the diagnosis of joint disease in early stage and provides evaluation on the effect of treatment. Moreover it offers a good example to research other diseases by using the biophysical characteristics of body fluid, which exhibit valuable significance to prevent, treat joint and other disease, and to investigate underlying mechanism of inter-relative diseases.
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