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Objective: Naringenin (NAR), a flavanone in citrus fruits, has been reported to have both anti-diabetic and anti-osteoporotic effects. This study aimed to explore the effect of NAR on bone homeostasis under diabetic condition. Methods: High fat diet and streptozotocin (STZ) induced type 1 diabetic (T1DM) and leptin receptor knockout (db/db) type 2 diabetic (T2DM) mice were used to evaluate NAR effects. Melbine (DMBG) was administrated as positive control. Body weight and fasting blood glucose were monitored weekly and monthly. After 8 weeks and 74 days treatment, bone mass was evaluated by microcomputed tomography ([Formula: see text]CT) including BV/TV, Tb.N, and Tb.Th, as well as histological and histomorphometric detection. Bone resorption rate indicated by C-terminal telopeptide of type I collagen (CTIX) and N-terminal propeptide of type I procollagen (PINP) was examined by ELISA assays. Results: NAR treatment reduced body weight and blood glucose in both diabetic models, and had better hypoglycemic effect than DMBG at early stage. High fat diet and STZ-treated mice lost while db/db mice gained bone mass. NAR improved bone microarchitecture by regulating the related parameters to the similar levels as the control. Osteoblast activity was little affected, but osteoclast function was decreased in NAR-treated STZ mice. Consistently, NAR reduced bone resorption rate which was increased in both diabetic models. Conclusion: NAR exerts an anti-diabetic effect by lowering elevated level of blood glucose, regulating impaired bone mass, and reducing overactivated bone resorption rate in T1DM and T2DM conditions. Naringenin has a potential to prevent diabetes induced impairment in bone.

Intervertebral disc degeneration (IDD) is a common pathological change leading to low back pain. Appropriate animal models are desired for understanding the pathological processes and evaluating new drugs. Here, we introduced a surgically induced lumbar spine instability (LSI) mouse model that develops IDD starting from 1 week post operation. In detail, the mouse under anesthesia was operated by low back skin incision, L3-L5 spinous processes exposure, detachment of paraspinous muscles, resection of processes and ligaments, and skin closure. L4-L5 IVDs were chosen for the observation. The LSI model develops lumbar IDD by porosity and hypertrophy in endplates at an early stage, decrease in intervertebral disc volume, shrinkage in nucleus pulposus at an intermediate stage, and bone loss in lumbar vertebrae (L5) at a later stage. The LSI mouse model has the advantages of strong operability, no requirement of special equipment, reproducibility, inexpensive, and relatively short period of IDD development. However, LSI operation is still a trauma that causes inflammation within the first week post operation. Thus, this animal model is suitable for study of lumbar IDD.

Allergic asthma is a common chronic inflammatory disease characterized by airway inflammation, mucus hypersecretion and airway remodeling. Autophagy is a highly conserved intracellular degradation pathway in eukaryotic cells. There is growing evidence suggesting that dysregulation of autophagy is involved in the pathological process of asthma. Luteolin is a typical flavonoid compound with anti-inflammatory, anti-allergic and immune-enhancing functions. Previous studies have shown that luteolin can attenuate airway inflammation and hypersensitivity in asthma. However, whether luteolin can play a role in treating asthma by regulating autophagy remains unclear. The aim of the present study was to evaluate the therapeutic effect of luteolin on ovalbumin (OVA)-induced asthmatic mice, observe its effect on the level of autophagy in lung tissues, and further elucidate its underlying mechanism. The results showed that OVA-induced mice developed airway hyperresponsiveness, mucus over-production and collagen deposition. The number of inflammatory cells, levels of interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and OVA-specific IgE in serum were significantly increased. Furthermore, the infiltration of inflammatory cells was observed along with the activation of autophagy in lung tissues. Luteolin treatment significantly inhibited the OVA-induced inflammatory responses and the level of autophagy in lung tissues as well. Moreover, luteolin activated the PI3K/Akt/mTOR pathway and inhibited the Beclin-1-PI3KC3 protein complex in lung tissues of asthmatic mice. In conclusion, this study explored the regulatory mechanism of luteolin on autophagy in allergic asthma, providing biologic evidence for its clinical application.

Angiotensin II (ANG II) might play an important role in the co-effects of cold stress and fine particulate matter (PM2.5) on chronic obstructive pulmonary disease (COPD). The purpose of this study is to evaluate the roles of valsartan in alleviating COPD following co-exposure to cold stress and PM2.5. Both the two intervention factors are carried out upon COPD rats with the intervention of valsartan. Blockade of angiotensin receptor by valsartan decreases the levels of malondialdehyde in the normal temperature and tumor necrosis factor-α under cold stress significantly. When treated with valsartan and PM2.5 simultaneously, the expression of 8-hydroxy-2-deoxyguanosine, nuclear factor kappa B and heme oxygenase-1 decrease significantly in the group of cold stress. In conclusion, these results indicate that valsartan might relieve the co-effects of cold stress and PM2.5 on COPD rat lung to some degree.

ObjectivesExamine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models.Methods3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone.ResultsHalofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone.ConclusionsHalofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA.

Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.

INTRODUCTION Information on the changes of pulmonary function and the right cardiac structure in patients with coal worker's pneumoconiosis in China is very scarce. This study was performed to clarify the changes of pulmonary function and right cardiac structure in patients with coal worker's pneumoconiosis in China. MATERIAL AND METHODS Pulmonary function, pulmonary artery systolic pressure, and the right cardiac structure were evaluated by spirometry and color Doppler echocardiography. RESULTS The pulmonary artery systolic pressure of patients with coal worker's pneumoconiosis was increased with disease severity. Patients with coal worker's pneumoconiosis also exhibited an impaired pulmonary function and altered right cardiac structure compared with control subjects. A significant linear correlation of the variables of pulmonary ventilation and diffusion function with the indicators of the right cardiac structure was found in patients with coal worker's pneumoconiosis in China. CONCLUSIONS This study elucidated a deterioration of pulmonary function and right cardiac structure in patients with coal worker's pneumoconiosis in China.

Traditional herbal medicine, an alternative medicine in the clinical setting, has received increased attention in recent years. Before delivery to the body, an additional extraction procedure is commonly required to release the active constituents from raw herbs. Water decoction is a classical extraction procedure that is still broadly used in the clinical settings. Here, we propose a detailed protocol for er-xian decoction (EXD) in order to apply herbal decoctions to experimental studies. The calculation of an animal-appropriate dose is described, as well as the four main steps of EXD: soaking, water decoction, filtration, and concentration. In addition, serum-containing EXD is introduced to rats as a means of in vitro validation. Here, rats were orally administered EXD for three days. Blood samples were then collected, inactivated, centrifuged, and filtered. The serum, diluted with the culture medium, can be utilized to treat cells or tissues in vitro. For example, EXD was applied to both in vivo and in vitro studies and demonstrated that EXD enhances osteogenesis. This protocol can be used as a reference for the preparation and application of herbal medicines.

Background Coal workers' pneumoconiosis (CWP) is characterized by progressive pulmonary fibrosis. Inflammation is crucial in the host response to silica and it contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process. The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene with pneumoconiosis risk was investigated. Methods An association study was conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2 (rs689466 and rs20417) in a case–control study involving 90 patients and 90 healthy individuals (controls). Genotyping was performed by the TaqMan method. Results The rs689466 AG and GG and rs689466 GC polymorphisms were significantly less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417 variant genotypes exhibited 21% and 12% decreased CWP risk, respectively. Conclusion Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated with CWP risk. Am. J. Ind. Med. 57:866–871, 2014. © 2014 Wiley Periodicals, Inc.

The Event Sequence Diagram (ESD) is a visualized method to describe sequences of related events. It has the characteristics of simple and powerful description ability which has great value in engineering application. According to the requirement of modeling and analysis in equipment maintenance support process, this paper introduces the basic factors of existing ESD framework, and generalizes the basic thought of establishment of ESD model; combining the characteristics of maintenance support system and resources, the expanding of ESD and its canonical definition were discussed. Based on it, this paper gives further research on the analysis method of maintenance support based on ESD, and the basic scheme of analyzing maintenance time and maintenance resource are provided. To some extent, it can solve the problems existing in traditional modeling method of equipment maintenance support process.With the rapid development of modern science and technology, many equipment performances improve constantly, at the same time, the overall complexity increases rapidly. Any changes could bring big impact on the reliability, safety and maintenance supportability of the system[1]. Maintenance support process is not only a simple static process, but a complex process which involves factors that interacts each other such as personnel, equipments, resource and external environment as well as those dynamic factors such as time, process variables and behavior of management and operating personnel. Although there are many maintenance support models at home and abroad, which include PERT, random network, Petri and IDEF3[2], etc, most of them establish related analytical models and simulation models in terms of cost and supportability parameter, which only focus on certain part of the maintenance support system or one aspect of its analysis. It has its characteristic as well as its limitation. Actually, as a complex system engineering process, it is more scientific and reasonable to establish process model completely and comprehensively according to the maintenance support process，which can not only complete the maintenance support analysis that traditional model does, but also can describe the support process accurately, and it can give maintenance support problems, such as support resource and maintenance activity, a bottom-up and detailed analysis.As a graphical simulation method to describe sequences of related events, ESD can be regarded as generalized event tree which characterized by visual, descriptive, manageable qualitatively and quantitatively, and can describe system accident scene truly as well as the relationship between event and personnel,resources, management and the other events [3]. At the same time, it can provide enough structure information for the system, which makes it being understood easily and applied in modeling research. This paper put forwards basic thought for ESD modeling based on the existing model frame, then, it is expanded and applied in equipment maintenance support process modeling and can complete the related analysis.

It is still uncertain whether total bilirubin per se is a risk factor for osteoporosis in postmenopausal women and no study has so far examined this important issue. This study was designed to assess the sheer effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease. In the present study, postmenopausal female subjects without potential liver disease (n = 918) who underwent measurement of bone mineral density were enrolled. Correlation and logistic regression analysis were used to assess the relationship between total bilirubin and other variables. As a result, subjects with osteoporosis had a significantly lower total bilirubin level (P = 0.005). A 0.1 mg/dl increase in total bilirubin was associated with reduced odds ratio of the risk by 38 % for osteoporosis [OR 0.62 (95 % CI 0.52–0.88), P = 0.012] after adjustment for several variables. Total bilirubin was independently associated with BMD [coefficient = 0.41, 95 % CI (0.35–0.47), P

AIMS Gamma glutamyltransferase (GGT) has attracted great interest as a potential novel marker of cardiovascular risk. However, its association with coronary artery calcification (CAC) score-determined coronary artery atherosclerosis is unknown. This study was designed to assess the association of GGT with CAC score. METHODS Participants, 311 asymptomatic men and 220 asymptomatic women who underwent evaluation of CAC by cardiac computed tomography, were retrospectively investigated. Correlation and logistic regression analysis were used to assess the association of GGT with CAC score and other variables. RESULTS Women but not men with higher GGT had a higher incidence of CAC score above 100 and a higher prevalence of metabolic syndrome (P = 0.012 and 0.007, respectively). GGT was positively correlated with C-reactive protein (CRP) in women (r = 0.336, P

Narrowed intervertebral disc (IVD) space is a characteristic of IVD degeneration. EP sclerosis is associated with IVD, however the pathogenesis of EP hypertrophy is poorly understood. Here, we employed two spine instability mouse models to investigate temporal and spatial EP changes associated with IVD volume, considering them as a functional unit. We found that aberrant mechanical loading leads to accelerated ossification and hypertrophy of EP, decreased IVD volume and increased activation of TGFβ. Overexpression of active TGFβ in CED mice showed a similar phenotype of spine instability model. Administration of TGFβ Receptor I inhibitor attenuates pathologic changes of EP and prevents IVD narrowing. The aberrant activation of TGFβ resulting in EPs hypertrophy-induced IVD space narrowing provides a pharmacologic target that could have therapeutic potential to delay DDD.

Objective Oleanolic acid (OA) and its glycosides have been reported to prevent bone loss by inhibiting the formation of osteoclasts. However, because bone formation and resorption are balanced processes in bone metabolism, no studies have described the effect of OA on osteogenesis. The aim of the present study was to evaluate the osteoprotective effect of OA in rats with ovariectomy (OVX)-induced osteoporosis and to search for the molecular targets of OA in bone mesenchymal stem cells (bMSCs). Methods Two-month-old female mice that underwent OVX were treated with OA (20 mg/kg a day). After 2 weeks and after 3 months, bone mass was evaluated by micro-CT, morphometry, and immunohistochemical detection. In addition, the expression of 256 genes was measured via microarray and confirmed by real-time reverse transcription-polymerase chain reaction. The effects of OA on the activities of bMSCs were also observed in vitro using alkaline phosphatase and cell proliferation assays. Results Micro-CT displayed only a tendency for bone loss at 2 weeks but a decrease in bone mass at 3 months after OVX. OA treatment increased osteoblast number, increasing osteocalcin and runt-related protein 2 protein levels in vivo and facilitating the osteoblastic differentiation of bMSCs in vitro at doses of 10(-6) and 10(-5) M. Gene expression profile analysis revealed that OVX caused a marked dysregulation of gene expression, especially at 2 weeks, some of which was rescued by OA. Few of these genes overlapped, but their functions were involved in the Notch signaling pathway between two phases of the osteoporotic process. Conclusions OA exerts an osteoprotective effect in OVX-induced osteoporotic rats and stimulates the osteoblastic differentiation of bMSCs in vitro. The molecular mechanism of this effect might be related to the Notch signaling pathway and requires further investigation.

Serum uric acid (SUA) is a potential risk factor for atherosclerosis. We assessed the relationship between SUA and subclinical atherosclerosis in Korean men (n = 3010). Multidetector computed tomography (MDCT) and ultrasonographic measurements of coronary artery calcification (CAC) and carotid intima–media thickness (cIMT), respectively, are markers of subclinical atherosclerosis. Odds ratios (ORs) of CAC score and cIMT across SUA levels were 1.101 ( P = .046) and 1.266 ( P = .002), respectively, after adjustment for several variables. The independent association between CAC and cIMT was observed (OR = 1.231, P < .001). Serum uric acid was independently associated with metabolic syndrome (MetS) with an OR of 1.415 ( P < .001). Metabolic syndrome was only independently associated with cIMT, with an OR of 2.103 ( P = .003). High-sensitivity C-reactive protein was positively correlated with SUA ( r = .125, P < .001). Serum uric acid level is independently associated with CAC, cIMT, and MetS in Korean men.

Considering the weapon materiel maintenance condition, intelligence theory and method such as expert system and neural network is introduced in BIT technology. BIT intelligence maintenance decision in materiel maintenance field is discussed. The realization of materiel intelligence BIT reflects the concurrent design concept of system exploitation. Level integrated intelligence BIT system organization framework is adopted. BIT comprehensive decision-making and maintenance expert system structure is designed, and its implementation plan based on BIT is offered, which can enhance the fault diagnosis capability of modern complicated weapon materiel.

The development of the permanent deformation of subgrade soils under repeated load tests may consists of three stages, namely the primary, secondary and tertiary stages, but the existing models can not describe this behavior very well, so a new model is required to be developed. Based on the creep equation of the soil under static load, a mechanistic model is developed to describe the development of the permanent deformation of the soil under repeated load tests. Triaxial repeated load tests are conducted for silty soils and results show that, under some conditions, the development of the permanent deformation of silty clay consists of three stages and the number of load repetitions corresponding to the initiation of the tertiary stage is 330,0000. The new model is used to fit the test results and the comparison of test results and fitting results prove that this model can describe all three stages of permanent deformation.

Of different model-based methods in vision based human tracking, many state of the art works focus on the stochastic optimization method to search in a very high dimensional space and try to find the optimal solution according to a proper likelihood function. Seldom works perform a framework of interactive multiple models (IMM) to track a human for challenging problems, such as uncertainty of motion styles, imprecise detection of feature points and ambiguity of joint location. This paper presents a two-layer filter framework based on IMM to track human motion. First, a method of model based points location is proposed to detect key feature points automatically and the filter in the first layer is performed to estimate the undetected points. Second, multiple models of motion are learned by the prior motion data with ridge regression and the IMM algorithm is used to estimate the quaternion vectors of joints rotation. Finally, experiments using real images sequences, simulation videos and 3D voxel data demonstrate that this human tracking framework is efficient.

Study design Several senescence biomarkers were observed to investigate cell senescence in degenerative intervertebral lumbar discs of foreleg-amputated rats. Objective To determine if cell senescence is accelerated in degenerative intervertebral lumbar disc cells in an upright-rat model. Summary of background data Cellular senescence was accelerated in human and sand rat degenerative intervertebral disc (IVD) cells. Repeated use of upright posture by rats contributed to degenerative disc changes. No convincing evidence of cell senescence was observed in the lumbar disc of the foreleg amputated rat. Methods The forelimbs of 20 rats were amputated at 1 month of age such that they maintained an upright stance; rats were housed in custom-made cages. Nonamputated rats, also 1 month of age, were kept in regular cages and served as a control group. The lumbar IVDs were harvested from rats in 2 groups, at 5 or 9 months following amputation. Senescence-associated-β-galactosidase-positive staining was used to detect cell senescence. p16INK4a and p27KIP were assessed by immunohistochemistry analysis. Total RNA isolated from these samples was used to measure the gene expression of p16INK4a, RB, cyclin D1, CDK4, PTEN, p27KIP, p19ARF, p21, TERT, and RAGE by real-time polymerase chain reaction assay. Results The highest levels of SA-β-GAL activity were detected in 9-month amputated rats. Quantitative immunohistochemical analysis showed that there were highest rates of p16INK4a and p27KIP protein expression in the cartilage endplate and anulus fibrosus of 9-month amputated rats. The mRNA levels of p16INK4a, RB, PTEN, p27KIP, p19ARF, and RAGE were upregulated. The increased cyclin D1 mRNA level was statistically significant only at the ninth month following amputation; CDK4 and TERT mRNA levels were downregulated to a similar extent at both points compared with nonamputated controls. mRNA expression of p21 was significantly downregulated. Conclusion Accelerated cell senescence was associated with forelimb amputation that causes abnormal loading in rat lumbar IVDs.

Objective To observe the effects of Qishe Pill, a compound traditional Chinese herbal medicine, on lumbar vertebral bone formation induced by long-time upright posture in rats and to investigate the potential mechanism. Methods Thirty SD rats were randomly divided into normal control group, untreated group and Qishe Pill group. The rats in normal control group received no treatment and were raised in normal cages. The rats in untreated group and Qishe Pill group were cut off forelimbs by operation so as to be forced to adopt an upright posture for 8 months to induce hyperostosis. Rats in the Qishe Pill group were intragastrically administered with Qishe Pill at a dose of 5 g/(kg x d) for 1 month. All rats were sacrificed at the 9th month after surgery and all lumbar vertebrae were harvested for detection. Safranin O/fast green staining and picrosirius red staining were used to observe pathological changes. Expressions of type I collagen (ColI), type X collagen (ColX), vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) in the 5th lumbar vertebra (L(5)) were detected by immunohistochemical method. Expressions of type I collagen alpha2 (Col1alpha2), type X collagen alpha1 (Col10alpha1), TGF-beta1, and VEGF and runt-related transcription factor 2 (Runx2) mRNAs in L(1)-L(3) were detected by real-time fluorescent quantitation reverse transcription-polymerase chain reaction. Results Safranin O/fast green staining showed that in the untreated group, non-matrix components increased at marginal lumbar vertebra and intervertebral disc junction, and hyperostosis appeared. However, no obvious change was observed in the normal control group. Non-matrix components decreased at the same location in Qishe Pill group as compared with the untreated group. Picrosirius red staining showed compact collagens at marginal lumbar vertebra and intervertebral disc junction in the normal control group, however, Col I and ColX increased at the same location in the untreated group. In the Qishe Pill group, it showed more compact collagens, especially ColI. Compared with normal control group, expressions of ColX, VEGF and TGF-beta1 were increased at marginal lumbar vertebra and intervertebral disc junction in the untreated group. ColX and VEGF expressions decreased in the Qishe Pill group as compared with the untreated group. Col10alpha1 and Runx2 mRNA expressions were down-regulated by Qishe Pill (P Conclusion Qishe Pill may delay hyperostosis at marginal lumbar vertebra and intervertebral disc junction, which may be related to reducing type X collagen and Runx2 expressions.

Degeneration of the lumbar spine plays an important role in most chronic low back pain. Prevention of lumbar intervertebral disc (IVD) degeneration is therefore a high research priority. Both our previous multicenter clinical trials and pharmacological research showed that Fufangqishe-Pill (FFQSP), a newly patented traditional Chinese medicine, could effectively relieve the symptoms of neck pain and prevent cervical degeneration. To clarify the effect of FFQSP on lumbar IVD degeneration, we applied a lumbar IVD degeneration rat model induced by prolonged upright posture. Pretreatment of FFQSP for one month prevented the histological changes indicating IVD disorganization; increased type II–collagen level, decreased type X–collagen protein level, and increased Col2α1 mRNA expression at all time points; and decreased Col10α1, matrix metalloproteinase (MMP)-3, MMP13, and Interleukin (IL)-1β mRNA expression induced by upright posture for 7 and 9 months. These results suggest that FFQSP prevents lumbar IVD degeneration induced by upright posture. FFQSP is a promising medicine for lumbar IVD degeneration disease. Keywords:: chronic low back pain, Fufangqishe-Pill, lumbar intervertebral disc degeneration, extracellular matrix

OBJECTIVE To explore the mechanism of Yiqi Huayu Bushen Recipe (YHBR), a compound traditional Chinese herbal medicine, in treating cervical syndrome (CS) with qi deficiency, blood stasis and kidney deficiency in rats. METHODS A total of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal control group, untreated group and YHBR group; there were ten rats in each group. The rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency was established by combining disease and syndrome models. After one-month YHBR treatment in YHBR group, all rats were sacrificed. Serum, plasma and cervical intervertebral discs were detected and observed by radio-immunology, histopathology, immunohistochemistry, etc. RESULTS Compared with those in the normal control group, rats in the untreated group showed obvious signs of deficiency in vital energy, such as tiredness, ptosis, few movement, bluish-purple tongue and tail and weight loss; the weight of uterus and appendages, and the ratio of cyclic adenosine monophosphate/cyclic guanosine monophosphate were decreased; hemorheological parameters and the expression of alpha-granular membrane protein (CD62p) were increased; the content of serum estradiol was decreased. YHBR could improve the above indexes except for the weight of uterus and appendages. HE staining showed annulus fibrosus with cracks, diminish of pulposus nucleus, and decrease in the height of intervertebral disc and the thickness of end-plate in the untreated group; and YHBR could improve the changes of cervical intervertebral discs, but no obvious changes in end-plate. Type II collagen protein (Col2a1)was distributed in every part of the annulus fibrosus in normal control group, but was decreased in untreated group; YHBR could increase Col2a1 expression in annulus fibrosus as compared with the untreated group. The expressions of Col2a1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were decreased in untreated group as compared with the normal control group (P

Study Design. Establishment of a novel in vivo animal model of cervical spondylosis. Objective. To investigate apoptotic, degenerative, and inflammatory changes occurring in the cervical intervertebral discs of rats. Summary of Background Data. Cervical degeneration occurs as the result of imbalance of both static and dynamic spinal stabilizers. The disc degeneration that occurs is characterized by increased local inflammation and increased apoptosis of intervertebral disc cells. Methods. By excising the paraspinal musculature and posterior cervical spinal ligaments of rats, both static and dynamic cervical stabilizers were disrupted. The resultant biomechanical imbalance resulted in biochemical and histologic changes, which were characterized by light microscopy, electron microscopy, immunostaining, enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization. Results. Histologic analysis showed characteristic degenerative changes of the intervertebral discs and vertebral endplates following surgery. Ultrastructural examination revealed apoptotic changes, which were verified by immunostaining. Instability also resulted in significant up-regulation of inflammatory factors, as shown by enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization. Conclusions. By creating static and dynamic posterior instability of the cervical spine, this novel model of cervical spondylosis results in rapid intervertebral disc degeneration characterized by increased apoptosis and local inflammation, such as that seen clinically.

Ambiguous pattern recognition is a very important technology in the field of science including engineering application nowadays, it uses methods of fuzzy mathematics enabling the computer to recognize and judge the objective things. But, the research on ambiguous pattern recognition rarely involves the field of security, while in fact both the participant of the pattern recognition and the database need to protect their privacy. This paper mainly introduces the secure multi-party computation into the field of ambiguous pattern recognition, raises solution for the secure multi factor ambiguous pattern recognition under the half honest model, and proves the validity and security of the protocol.

Psoralea corylifolia extract has been reported to promote bone formation in osteoporotic animals. Psoralen (PSO), a flavonoid glycoside, as the active component of P corylifolia L, is effective in increasing new bone-forming osteoblasts in parietal bone defects. However, the effect and molecular mechanisms of PSO on bone mesenchymal stem cells (bMSCs) in the osteoporotic state are widely unknown. This study was designed to evaluate the osteoprotective effect of PSO in ovariectomy (OVX)-induced rats and to seek possible molecular mechanisms of PSO in bMSCs.We observed the osteogenic effect of PSO (3-month treatment) on osteoporotic rat models induced by OVX via testing bone densitometry, histomorphometries, and immunohistochemistry in vivo. Alkaline phosphatase staining and colony-forming unit-fibroblast and colony-forming unit-adipocyte assays were performed to evaluate the differentiation potential of bMSCs ex vivo. In addition, the molecular targets of PSO in bMSCs were detected by stem cell microarray analysis of 256 genes and confirmed by real-time reverse transcription-polymerase chain reaction.Micro-CT morphometry analysis showed that PSO significantly improved bone mass indicators including increased trabecular thickness and decreased trabecular space. Meanwhile, PSO elevated the well-known osteogenic marker osteocalcin level in OVX-induced osteoporotic rats. Next, in ex vivo studies, we revealed that PSO facilitated alkaline phosphatase staining and increased the colony-forming unit-fibroblasts. Based on gene expression profile analysis, we screened a set of genes dysregulated in OVX but reversed by PSO treatment. These genes were highly enriched in the Notch signaling pathway, which was documented to play a role in bMSC differentiation.Our findings show that PSO promotes bone mass in OVX-induced osteoporotic rats. This effect of PSO is highly related to the stimulation of differentiation of bMSCs to osteoblasts.

Serum total bilirubin has been suggested to have the potential anti-inflammatory and antioxidant effects on the vasculature. This study was designed to investigate the association of bilirubin with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and cardiovascular disease. Hypertensive male subjects (n = 2,361) were classified into groups according to the 50th, 75th, and 95th percentiles of baPWV value. Correlation and regression analysis were used to assess the relationship between baPWV and other variables. Hypertensive subjects with baPWV above the 50th, 75th, and 95th percentiles had a significantly lower bilirubin level than those with baPWV under them (0.97 ± 0.40 vs. 1.00 ± 0.41 mg/dl, P < 0.001; 0.95 ± 0.39 vs. 0.99 ± 0.41 mg/dl, P = 0.001; 0.92 ± 0.36 vs. 0.99 ± 0.42 mg/dl, P = 0.048, respectively). Bilirubin is inversely related to baPWV (R (2) = 0.0032, P = 0.003) and C-reactive protein (CRP) (correlation coefficient = -0.13, P < 0.001). A 0.1 mg/dl increase in bilirubin was associated with a 19, 20, and 34 % reduced odds ratio for baPWV above the 50th, 75th, and 95th percentiles, respectively [odds ratio (OR) 0.77 (95 % confidence interval (CI) 0.62-0.95), P = 0.015; OR 0.80 (95 % CI 0.64-0.99), P = 0.044; OR 0.68 (95 % CI 0.45-1.00), P = 0.048, respectively] after adjustment for several variables. This study demonstrates an independent inverse association between bilirubin and baPWV in hypertensive men. Additionally, reduced CRP may be one of mediators on the mechanisms how bilirubin reduces baPWV.

Background: Serum total bilirubin has been suggested to have potential anti-inflammatory and antioxidant effects on the vasculature, acting against plaque formation and subsequent atherosclerosis. This study was designed to assess the association of serum total bilirubin with coronary artery calcification (CAC). Hypothesis: Individuals with higher bilirubin level would be less likely to develop CAC. Methods: Male subjects (N = 3408) underwent evaluation of CAC by cardiac computed tomography. Correlation and logistic regression analysis were performed to assess the relationships between CAC score and other variables. Results: Subjects with a higher CAC score had significantly lower total bilirubin level (P = 0.001). Total bilirubin level was negatively correlated with CAC score (r = −0.052, P = 0.002). A 0.1-mg/dL increase in bilirubin was associated with a reduced odds ratio (OR) of the risk by 29.2% for a CAC score above 100 (OR: 0.708, 95% confidence interval: 0.542-0.927, P = 0.012) after adjustment for several variables. Bilirubin was inversely correlated with high-sensitivity C-reactive protein (hsCRP) (r = −0.117, P < 0.001). Conclusions: This study demonstrated an independent inverse association between serum total bilirubin and CAC score in males. Low serum bilirubin concentration would be useful as a potential risk factor for CAC in males. Additionally, reduced hsCRP may be 1 of the mechanisms for how bilirubin reduces CAC. © 2012 Wiley Periodicals, Inc. Additional Supporting Information may be found in the online version of this article. Zheng-Yun Zhang, MD, and Lu-Qin Bian, MD, contributed equally to this work. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Ethnopharmacological relevance Icariin represents an important active component in Herba Epimedii , which is a famous Chinese herbal medicine that is widely used to treat some age-related diseases in oriental countries. Objective The aim of this work was to investigate the effects of icariin on cognitive function in natural aging rats, and then to explore its mechanism by investigating the activation of quiescent neural stem cells (NSCs) in the hippocampus. Materials and methods Sprague-Dawley rats that were 18 months of age were divided into two groups including treated rats (i.e., icariin was administered from the age of 18 months to 21 months) and control rats (i.e., only saline was administered). The Morris water maze (MWM) tasks were then employed to measure spatial learning and memory. Subsequently, AraC was infused into the brain with osmotic minipumps in order to destroy proliferative stem cells primarily leaving quiescent NSCs. After seven days of recovery, 5-bromodeoxyuridine (BrdU) was co-labeled with markers for NSC to identify NSCs. Results The results from the MWM indicated that icariin has a beneficial effect on cognitive function in aging rats. In addition, by double-labeling BrdU and glial fibrillary acidic protein (GFAP), our findings indicated that NSC activation is markedly increased in the icariin-treated rats compared to control rats. For example, a much greater increase was produced in BrdU and highly polysialylated neural cell adhesion molecule (PSA-NCAM) and BrdU and Olig2 double-labeled cells following icariin treatment. Conclusion Our findings suggest that icariin represents a promising candidate for the modulation of aging. Therefore, icariin administration may effectively prevent or delay the onset of age-related cognitive degeneration, and its capability to activate quiescent NSCs may potentially be one of its mechanisms.

Background Osteoporosis is a growing worldwide problem, with the greatest burden resulting from fractures. Nevertheless, the majority of fractures in adults occur in those with "osteopenia" (bone mineral density (BMD) only moderately lower than young normal individuals). Since long-term drug therapy is an expensive option with uncertain consequences and side effects, natural herbal therapy offers an attractive alternative. The purpose of this study is to evaluate the effect on BMD and safety of the Classic Yin and Yang Tonic Formula for treatment of osteopenia and to investigate the mechanism by which this efficacy is achieved. Methods/design We propose a multicenter double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of the Classic Yin and Yang Tonic Formula for the treatment of osteopenia. Participants aged 55 to 75 with low bone mineral density (T-score between -1 and -2.5) and kidney deficiency in TCM will be included and randomly allocated into two groups: treatment group and control group. Participants in the treatment group will be treated with Classic Yin and Yang Tonic Granule, while the controlled group will receive placebo. Primary outcome measure will be BMD of the lumbar spine and proximal femur using dual-energy X-ray absorptiometry. Secondary outcomes will include pain intensity measured with visual analogue scales, quality of life, serum markers of bone metabolism, indices of Neuro-endocrino-immune network and safety. Discussion If the Classic Yin and Yang Tonic Formula can increase bone mass without adverse effects, it may be a novel strategy for the treatment of osteoporosis. Furthermore, the mechanism of the Chinese medical formula for osteoporosis will be partially elucidated. Trial registration This study is registered at ClinicalTrials.gov, NCT01271647.

Study Design. Both forelimbs of rats were amputated and these rats were kept in the custom-made cages to keep prolonged and repeated upright posture. Changes of bone were observed in the lumbar vertebrae at three different time points after the surgery. Objective. To investigate the effect of prolonged and repeated upright posture on the cartilage end plate of rat lumbar vertebrae. Summary of Background Data. Previous studies show calcified hypertrophy is related to mechanical stress, but there are no clear evidences to indicate whether or not long-term and repeated assumption of the upright posture could result in calcified hypertrophy in cartilage end plate of rat lumbar spine. Methods. The forelimbs of 30 rats were amputated when they were 1 month old. These rats were kept in the custom-made cages and were forced to stand upright on their hind-limbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were killed at 5, 7, and 9 months after the surgery and lumbar vertebrae samples were harvested for micro-CT, histologic, and immunohistochemical studies. Total RNA isolated from these samples were used for real-time RT-PCR of type X collagen (Col10α1), vascular endothelial growth factor (VEGF), and transforming growth factor β1 (TGF-β1). Results. Micro-CT showed increased inner part of cartilage end plate. Histologic revealed peripheral hypertrophy of disc after the surgery. Immunostaining and real-time RT-PCR showed increased protein and mRNA expression of type X collagen, VEGF, and TGF-β1. Conclusion. Prolonged upright posture induces cartilage end plate calcification and hypertrophy in rat lumbar spine.

Study design Both forelimbs of rats were amputated and these rats were kept in the custom-made cages to keep prolonged and repeated upright posture. Changes of bone were observed in the lumbar vertebrae at three different time points after the surgery. OBJECTIVE.: To investigate the effect of prolonged and repeated upright posture on bone formation of rat lumbar vertebrae. Summary of background data Previous studies show long-term and repeated load-induced bone formation, but there are no clear evidences to indicate whether or not long-term and repeated assumption of the upright posture could result in bone formation at rat lumbar vertebrae. Methods The forelimbs of 30 rats were amputated when they were 1 month old. These rats were kept in the custom-made cages and were forced to stand upright on their hindlimbs and tails to obtain water and food. Normal rats of the same ages kept in regular cages were used as control. The rats were sacrificed at 5, 7, and 9 months after the surgery and lumbar vertebrae samples were harvested for micro-computed tomographic (CT), histological, and immunohistochemical studies. Total RNA isolated from these samples were used for real-time polymerase chain reaction of type I collagen (Col1α2), type X collagen (Col10α1), transforming growth factor-β1 (TGF-β1) and its related nuclear transcript factor runt-related transcription factor 2 (Runx2), as well as the biomarker of angiogenesis and vascular invasion, which is also a prerequisite for endochondral bone formation: vascular endothelial growth factor (VEGF). Results Micro-CT and histological studies showed increased trabecular bone density and increased osteoblast quantities of lumbar vertebrae after surgery. Immunostaining revealed increased protein expression of type I collagen, type X collagen, TGF-β, and VEGF. Real-time polymerase chain reaction showed upregulated expression of Col1α2, Col10α1, VEGF, TGF-β1, and Runx2 mRNA. Conclusion Upright posture induces bone acquisition in the rats' lumbar spine, primarily through the mode of the endochondral ossification, which is associated with increased loading, activated VEGF, and TGF-β1 signaling.

Objective To establish a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency. Methods A total of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal group, cervical syndrome group and cervical syndrome with qi deficiency, blood stasis and kidney deficiency group (combined group), with 10 rats in each group. Rats in the normal group received no treatment, rats in cervical syndrome group underwent resection of cervical muscles and ligaments as unbalanced dynamic and static animal model, and rats in combined group underwent resection of both cervical muscles and ovaries, swimming and irregular diet, and injection of adrenal cortex hormone and adrenaline two and a half months after resection as combined model. The qi deficiency, blood stasis and kidney deficiency were determined by observing behaviors and physical signs of the rats, detecting the contents of plasma cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), the hemorrheology, the expression of alpha-granular membrane protein (CD62p) and the serum estradiol (E(2)) content. The aggrecan-1, type II procollagen gene (Col2a1), matrix metalloproteinases-13 (MMP-13) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs in cervical intervertebral discs were detected by histopathology, immunohistochemistry and real-time polymerase chain reaction. The cataplasia of the intervertebral discs was determined by detecting the histopathology, the expressions of type II collagen and type X collegen proteins, and the expressions of aggrecan-1 (Agc1), type II procollagen gene (Col2a1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs. Results Compared with those in the normal group and cervical syndrome group, the rats in the combined group were noted with obvious signs of deficiency of vital energy, such as depression, tiredness, ptosis, obvious weight loss and blue tail. And the ratio of cAMP/cGMP was decreased; the reducing viscosity was significantly up-regulated; the expression of CD62p was increased; the content of serum E(2) was decreased; the intervertebral disc structure was destructed; the cervical intervertebral disc was more seriously deteriorated. There exhibited a decrease in type II collagen protein expression, an increase in type X collagen protein expression, as well as decreases of Agc1, Col2a1 and TIMP-1 mRNA expressions in intervertebral disc, and the expression of MMP-13 mRNA was noted an increase. Conclusion The rat model of cervical syndrome with qi-deficiency, blood stasis and kidney deficiency is established. Qi deficiency, blood stasis and kidney deficiency can aggravate cervical intervertebral disc degeneration.

OBJECTIVE To study the efficacy and possible mechanism of Yiqi Huayu Recipe (YQHYR), a compound traditional Chinese herbal medicine, in preventing and treating degeneration of the articular cartilage in rats with osteoarthritis (OA). METHODS A total of 90 one-month-old SD rats were randomly divided into normal control group, untreated group and YQHYR group, with 30 rats in each group. The osteoarthritis was induced by shoulder disarticulation plus upright posture in rats. The rats in YQHYR group were treated with YQHYR at 5-, 7- and 9-month old (4, 6 and 8 months after the surgery) for one month. Ten rats in each subgroup were sacrificed at 6-, 8- and 10-month old (5, 7 and 9 months after the surgery) respectively and the knee joint samples were harvested for detection. Safranin-O/fast green staining was performed to examine the morphology of articular cartilage. The expressions of type II collagen (Col2A1), aggrecan-1 (Agc1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were evaluated by real-time fluorescent quantitation polymerase chain reaction. RESULTS Histological analysis showed that the structure of articular cartilage was seriously destroyed in rats in the untreated group. On the contrary, the degenerative changes of the articular cartilage in the YQHYR group were dropped off. Real-time fluorescent quantitation polymerase chain reaction showed that expressions of Agc1, TIMP-1 and Col2A1 mRNAs were up-regulated in 6- and 10-month-old rats in the YQHYR group as compared with those in the untreated group (P

Osteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage and subchondral bone accompanied by low-grade inflammation that together result in pain and deformity. Recent studies have shed light on the nature of OA genetic susceptibility and confirmed a number of candidate genes involved in the destruction of the synovium, articular cartilage, and subchondral bone in OA pathogenesis. During the progression of OA, there are several cellular changes in joints, including an increase in the number of activated osteoclasts and macrophages and an infiltration of the synovium by activated T-cells and B-cells. Pro-inflammatory mediators (e.g. interleukin IL-1, IL-1beta, IL-6, IL-17, and IL-18, and Tumor necrosis actor-alpha), proteinases (e.g. matrix metalloproteinase 9 and cathepsin K), and regulators of cartilage and bone formation (e.g. BMPs) have been shown to have important roles in OA progression at the molecular level. Studies have suggested that OA shares several common characteristics with rheumatoid arthritis (RA). To systematically understand OA, this review summarizes OA disease genes, mouse models of human disease experimental mouse models, mechanisms of OA pathogenesis, and current OA therapies.