Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway.

OBJECTIVE: To investigate the effects of acupotomy on the subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis (KOA). METHODS: The rabbits were divided into blank control, model, acupotomy and electroacupuncture (EA) groups, with 12 rabbits in each. Modified Videman's method was used to prepare KOA model. The acupotomy and EA group were given indicated intervention for 3 weeks. The behavior of rabbits in each group was recorded. Subsequently, cartilage-subchondral bone units were obtained and morphological changes were observed by optical microscope and micro computed tomography. Compression test was used to detect the mechanical properties of subchondral bone, Western blot and real-time polymerase chain reaction (RT-PCR) were applied to detect the expression of bone morphogenetic protein 2-Smad1 (BMP2-Smad1) pathway in subchondral bone. RESULTS: Compared with the control group, rabbits in the KOA group showed lameness, knee pain, and cartilage degradation; the subchondral bone showed active resorption, the mechanical properties decreased significantly and the BMP2-Smad1 pathway downregulated significantly. Both acupotomy and EA intervention could increase the thickness of trabecular bone (Tb. Th), the bone volume fraction (BV/TV) and the thickness of subchondral bone plate, reduce the separation of trabecular bone (Tb. Sp), improve the maximum load and elastic modulus of subchondral bone, and effectively delay cartilage degeneration in KOA rabbits. This process may be achieved through upregulation the related proteins of BMP2-Smad1 pathway. The maximum load and elastic modulus of subchondral bone in the acupotomy group were slightly better than those in the EA group. CONCLUSIONS: Acupotomy could effectively protect cartilage by inhibiting abnormal bone resorption and improving mechanical properties of subchondral bone thorough the related proteins of BMP2-Smad1 pathway in KOA rabbits.

Unraveling the Phase Stability and Physical Property of Modulated Martensite in Ni2Mn1.5In0.5 Alloys by First-Principles Calculations.

Large magnetic field-induced strains can be achieved in modulated martensite for Ni-Mn-In alloys; however, the metastability of the modulated martensite imposes serious constraints on the ability of these alloys to serve as promising sensor and actuator materials. The phase stability, magnetic properties, and electronic structure of the modulated martensite in the Ni2Mn1.5In0.5 alloy are systematically investigated. Results show that the 6M and 5M martensites are metastable and will eventually transform to the NM martensite with the lowest total energy in the Ni2Mn1.5In0.5 alloy. The physical properties of the incommensurate 7M modulated martensite (7M-IC) and nanotwinned 7M martensite (7M-(52¯)2) are also calculated. The austenite (A) and 7M-(52¯)2 phases are ferromagnetic (FM), whereas the 5M, 6M, and NM martensites are ferrimagnetic (FIM), and the FM coexists with the FIM state in the 7M-IC martensite. The calculated electronic structure demonstrates that the splitting of Jahn-Teller effect and the strong Ni-Mn bonding interaction lead to the enhancement of structural stability.

Transcriptome analysis revealing molecular mechanisms of enhanced pigment yield by succinic acid and fluconazole.

This study aimed to elucidate the molecular mechanisms through which succinic acid and fluconazole stimulate Monascus pigment biosynthesis under liquid fermentation conditions. The pigment yield was significantly improved by adding 0.35 g·L-1 succinic acid or 1.5 g·L-1 fluconazole. Transcriptome sequencing and RT-qPCR confirmation were performed to reveal transcriptome changes. The results indicated that the addition of succinic acid significantly decreased mRNA expression of genes involved in fatty acid biosynthesis while increasing expression of genes involved in pyruvate metabolism. Fluconazole significantly down-regulated transcripts involved in branched-chain amino acid metabolism, fatty acid metabolism, glycolysis/gluconeogenesis, and pyruvate metabolism, as well as the generation of acetyl-CoA for pigment biosynthesis. On the other hand, nitrogen metabolism and lysine degradation pathways were significantly enriched, which could stimulate the generation of acetyl-CoA. Therefore, the mechanism for enhancing pigment yield may be attributed to the competitive regulation of metabolic pathways toward acetyl-CoA biosynthesis. Additionally, up-regulation of some different key genes in the presence of fluconazole or succinic acid was involved in improving pigment production. This study deepens the theoretical understanding for enhancing pigment biosynthesis and provides a few potential approaches for improving pigment yield.

Author Correction: Neighbor-Neighbor Correlations Explain Measurement Bias in Networks.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Degree correlations amplify the growth of cascades in networks.

Networks facilitate the spread of cascades, allowing a local perturbation to percolate via interactions between nodes and their neighbors. We investigate how network structure affects the dynamics of a spreading cascade. By accounting for the joint degree distribution of a network within a generating function framework, we can quantify how degree correlations affect both the onset of global cascades and the propensity of nodes of specific degree class to trigger large cascades. However, not all degree correlations are equally important in a spreading process. We introduce a new measure of degree assortativity that accounts for correlations among nodes relevant to a spreading cascade. We show that the critical point defining the onset of global cascades has a monotone relationship to this new assortativity measure. In addition, we show that the choice of nodes to seed the largest cascades is strongly affected by degree correlations. Contrary to traditional wisdom, when degree assortativity is positive, low degree nodes are more likely to generate largest cascades. Our work suggests that it may be possible to tailor spreading processes by manipulating the higher-order structure of networks.

Neighbor-Neighbor Correlations Explain Measurement Bias in Networks.

In numerous physical models on networks, dynamics are based on interactions that exclusively involve properties of a node's nearest neighbors. However, a node's local view of its neighbors may systematically bias perceptions of network connectivity or the prevalence of certain traits. We investigate the strong friendship paradox, which occurs when the majority of a node's neighbors have more neighbors than does the node itself. We develop a model to predict the magnitude of the paradox, showing that it is enhanced by negative correlations between degrees of neighboring nodes. We then show that by including neighbor-neighbor correlations, which are degree correlations one step beyond those of neighboring nodes, we accurately predict the impact of the strong friendship paradox in real-world networks. Understanding how the paradox biases local observations can inform better measurements of network structure and our understanding of collective phenomena.

Study on the tolerance and adaptation of rats to Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis (A. cantonensis) is the most common infectious agent causing eosinophilic meningitis. As an important food-borne parasitic disease, angiostrongyliasis cantonensis is an emerging infectious disease which brings severe harm to central nerve system of human. Rat, one of the few permissive hosts of A. cantonensis known to date, plays an indispensable role in the worm's life cycle. However, the tolerance and adaptation of rat to A. cantonensis infection is rarely understood. In this study, we infected rats with different numbers the third stage larvae (L3) of A. cantonensis and explored their tolerance through analysis on survival curve, neurological function score, and detection of pathological damages in organs including the brain, lung, and heart of the animals. Results indicated that rats' survival condition worsens, and body weight dropped more significantly as more worms were used for infection. Death appeared in groups infected with 80 and more A. cantonesnsis per rat. Morris water maze revealed that the neurological function of rats damaged gradually with increasing infection number of A. cantonensis larvae. When the number of infected parasite exceeded 240 per animal, rats showed significant neurological impairments. Collection of A. cantonensis from rat lung after 35 days of infection implied an upper limit for worm entry, and the average length of worm was inversely proportional to the infection amount, while the ratio between female and male worms was positively related to the infection number. The degree of pulmonary and cardiac inflammation was proportional to the infection number of A. cantonensis. Meanwhile, there existed considerable amount of adult worms in rat's right atrium and right ventricle, leading to a right heart myocardial inflammation. The present study firstly reports the tolerance and adaptation of rat, a permissive host of A. cantonensis to its infection, which will not only provide accurate technical parameters for maintaining A. cantonensis life cycle under laboratory conditions but also help unveil the underlying mechanism of the distinct pathological outcomes in the permissive and non-permissive hosts with A. cantonensis infection.

Inhibiting Interleukin 17 Can Ameliorate the Demyelination Caused by A. cantonensis via iNOS Inhibition.

Angiostrongylus cantonensis (A. cantonensis) is an important food-borne parasitic disease. Previous study showed that A. cantonensis infection can cause demyelination in the central nerve system, but the mechanism of action has not been understood. To explore the mechanism and to look for effective therapeutic methods, interleukin 17A (IL-17A) and iNOS expressions were detected during A. cantonensis infection. In addition, IL-17A-neutralizing antibody was applied to treat A. cantonensis-infected mice. In our results, we found that IL-17A and iNOS RNA expressions increased gradually in the process of A. cantonensis infection. When infected mice were treated with IL-17A-neutralizing antibody, the pathologic changes of demyelination alleviated obviously, followed with the elevation of myelin basic protein (MBP) in the brain. In addition, the iNOS expression of the brain in infected animals also showed a decrease in astrocytes. Our study provided evidence that IL-17A may take part in the demyelination caused by A. cantonensis and inhibiting IL-17A expression can ameliorate the pathologic changes of demyelination. Moreover, the decreasing of iNOS expression may be the key reason for the effect of IL-17A inhibition on demyelination caused by A. cantonensis.

Computed tomography angiography and magnetic resonance imaging performance of acute segmental single compartment syndrome following an Achilles tendon repair: A case report and literature review.

Acute compartment syndrome of the lower extremity is a serious postinjury complication that requires emergency treatment. Early diagnosis is of paramount importance for a good outcome. Four muscle compartments in the calf (anterior, lateral, deep posterior, and superficial posterior) may be individually or collectively affected. Acute segmental single-compartment syndrome is an extremely rare condition characterized by high pressure in a single compartment space with threatening of the segmental tissue viability. In this case report, we describe a young man with Achilles tendon rupture who complained of postoperative pain in the anterior tibial region. Emergent computed tomography angiography and magnetic resonance imaging revealed local muscle edema. Segmental anterior compartment syndrome was diagnosed and fasciotomy was performed.

The "Majority Illusion" in Social Networks.

Individual's decisions, from what product to buy to whether to engage in risky behavior, often depend on the choices, behaviors, or states of other people. People, however, rarely have global knowledge of the states of others, but must estimate them from the local observations of their social contacts. Network structure can significantly distort individual's local observations. Under some conditions, a state that is globally rare in a network may be dramatically over-represented in the local neighborhoods of many individuals. This effect, which we call the "majority illusion," leads individuals to systematically overestimate the prevalence of that state, which may accelerate the spread of social contagions. We develop a statistical model that quantifies this effect and validate it with measurements in synthetic and real-world networks. We show that the illusion is exacerbated in networks with a heterogeneous degree distribution and disassortative structure.

[Research progress on the risk factors of geographic tongue].

Geographic tongue, also called benign migratory glossitis, is a common and superficial benign inflammatory disorder that affects the tongue epithelium. The majority of geographic tongue lesions typically manifest as irregular central erythematous patches. These lesions, which are caused by the loss of filiform papillae, are defined by an elevated whitish band-like border that can change location, size, and pattern over a period of time. Histological observations of the oral mucosa affected by geographic tongue revealed nonspecific inflammation. Some reports described cases of migratory stomatitis, wherein lesions simultaneously manifested on the extra lingual oral mucosa. This condition is also called ectopic geographic tongue, which is clinically and histologically similar to the type normally confined to the tongue. In most cases, patients are asymptomatic and do not require treatment. The condition may spontaneously exhibit periods of remission and exacerbation with good prognosis. The specific etiology of geographic tongue remains unknown. Geographic tongue is age-related and is prevalent among young individuals. Various etiological factors that have been suggested in literature include immunological factors, genetic factors, atopic or allergic tendency, emotional stress, tobacco consumption, hormonal disturbances, and zinc deficiency. Geographic tongue may coexist with other disorders, such as fissured tongue, psoriasis, diabetes mellitus, gastroin- testinal diseases, burning mouth syndrome, and Down syndrome. Experts currently disagree on whether geographic tongue is an oral manifestation of psoriasis. Moreover, some scholars suggest that geographic tongue is a prestage of fissured tongue. The objective of this review is to summarize current research on risk factors of geographic tongue.

Gambogic acid inhibits invasion of osteosarcoma via upregulation of TIMP-1.

Gambogic acid (GA), the natural product, has been demonstrated to be a promising chemotherapeutic drug for osteosarcoma (OS) due to its ability to induce apoptosis and cell cycle arrest. To date, no studies have examined the role of GA in metastatic bone disease. Matrix metalloproteinases (MMPs) play critical roles in invasion and metastasis, and the tissue inhibitors of metalloproteinase (TIMP) family regulates the activity of multifunctional metalloproteinases. In this study, we investigated the gene expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in OS cell lines treated by the GA. The expression of MMP-9 and TIMP-1 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. In vitro invasion of OS cell lines (Saos-2, MG-63) were investigated by the Matrigel invasion assay. Mean MMP-9 protein and mRNA expression was significantly suppressed; in addition, mean TIMP-1 protein mRNA expression were upregulated by increasing GA concentrations. GA reduced the invasiveness of OS cell lines dose-dependently. Furthermore, specific inhibition of TIMP-1 secretion with siRNA against TIMP-1 significantly reduced the effect of GA on OS cell lines. Overall, our findings suggest that GA reduces the invasive potential of OS cells via attenuation of MMP-9 and upregulation of TIMP-1. Moreover, TIMP-1 played an important role in the reduction of invasive potential of the OS cells which were treated by GA.

Pure alumina bearings with cementless stems versus sandwich bearings with cemented stems in total hip arthroplasty.

BACKGROUND: Ceramic bearing surfaces have been introduced to prevent osteolysis after total hip arthroplasty (THA), but little is known about the difference in clinical and radiological results between pure alumina and sandwich alumina bearings. The purpose of this study was to analyze the results obtained with third-generation alumina-on-alumina THA with two different designs both in liner and femoral stem fixation after a minimum follow-up of 4.2 years. METHODS: The results of 195 primary alumina-on-alumina THAs in 167 patients were evaluated. The procedures were performed between January 1998 and October 2006. Three patients died and 11 patients were lost to follow-up, leaving a total of 153 patients (181 hips) available for study. In the 88 group A patients, 107 hips were implanted using pure alumina bearings with cementless femoral stems. These patients were followed for (6.84 ± 1.49) years. In the 65 group B patients, 74 hips were implanted using sandwich alumina ceramic bearings with cemented femoral stems. These patients had a follow-up period of (7.73 ± 1.60) years. Patients in both groups were evaluated clinically and radiographically. RESULTS: One ceramic liner fracture occurred in group A and five took place in group B (P < 0.05), four of them revised for liner fracture. In each group, one acetabular shell migration happened without liner breakage and two hips developed deep infections, and all these six hips received revisions. Nine femoral components loosened in group B, with seven undergoing revisions. Kaplan-Meier survivorship at 5 years for revision of any component for any reason in group A was 96.26% compared to 90.54% in group B (P < 0.05). Better function was determined in group A (average Harris hip scores: 92.13 ± 2.85) than in group B (average Harris hip scores: 86.03 ± 4.21) and the difference was significant (P < 0.05). Squeaking was not recorded in either group. CONCLUSIONS: The sandwich design of the acetabular bearings can not reduce the migration rate in ceramic bearings but increase the liner fracture rate compared to pure ceramic liners. The high loosening rate in fluted and taped designed cemented stems with sandwich liners warrant caution to their use.

[Analgesic and anti-inflammatory effects of Hanshibi tablet in mice and its effect on synovial pathology in a rat model of rheumatoid arthritis].

OBJECTIVE: To evaluate the analgesic and anti-inflammatory effects of Hanshibi tablet in Kunming mice and the effect of the tablet in ameliorating synovial pathology in a rat model of rheumatoid arthritis (RA). METHODS: Stretching test, capillary permeability and ear swelling test of Kunming were performed to observe the analgesic and anti-inflammatory effects of Hanshibi tablet administered intragastrically at different doses. In a SD rat model of RA induced by heat-inactivated Mycobacterium tuberculolytic H37Ra (Mtb), the effect of the tablet on the symptoms and progression of arthritis was observed regularly, and the numbers of the peripheral white blood cells, platelets and lymphocytes and mononuclear cells were measured. HE staining was used to examine the pathology of the rat ankle, and flow cytometry performed to monitor the changes in the T lymphocyte subsets. RESULTS: Hanshibi tablet treatment reduced the writhing response frequency and prolonged the stretching latency of Kunming mice. The tablet also inhibited the acetic acid-induced increase in capillary permeability and ear swelling. In the rat model of RA, administration of the tablet resulted in reduced ratio of CD4(+)/CD8(+), and significantly ameliorated synovial pathology. CONCLUSION: Hanshibi tablet has obvious analgesic and anti-inflammatory effects and ameliorates the synovial pathology in the rat model of RA possibly by regulating CD4(+)/CD8(+) balance.

Regeneration of the fibula using a periosteum-preserving technique in children.

Bone grafting is a commonly used surgical procedure, particularly in reconstructive orthopedic surgery. Bone grafts may be used to fill skeletal defects created by trauma, infection, tumors, or congenital malformation. Fibular graft is an ideal option and is widely used to treat massive segmental defects; however, it leads to various complications, especially in children. This article describes our experience with donor site bone grafts using a periosteum-preserving technique with respect to minimizing donor site complications and performing effective reconstruction of bone defects in children. Seventeen patients who were followed after fibula resection and bone grafting in the donor site using a periosteum-preserving technique were evaluated radiologically and clinically. The patients were divided into 2 groups: 1 group was filled with cancellous allograft (n=9), and the other group was filled with calcium sulfate (n=8) in the donor site. Mean patient age was 8.4 years (range, 2-13 years), and mean follow-up was 31 months (range, 7-65 months). Complete regeneration of the donor sites occurred in all patients; mean time to regeneration at donor sites was 12 weeks (range, 4-21 weeks). There were no significant donor site complications intraoperatively or immediately postoperatively. The average regeneration index was 0.5 (range, 0.2-1.1), and it was found to increase with age (r=0.75, P<.001), indicating that younger patients had faster regeneration. The periosteum-preserving technique was found to lead to the reconstruction of bone defects effectively in children with minimal donor site complications.

Risedronate inhibits human osteosarcoma cell invasion.

BACKGROUND: Osteosarcoma is a highly malignant bone tumor and is the most commonly encountered malignant bone tumor in children and adolescents. Furthermore, significant numbers of patients eventually develop pulmonary metastases and succumb to the disease even after conventional multi-agent chemotherapy and surgical excision. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs), which have a profound effect on bone resorption, are widely used to treat osteoclast-mediated bone diseases. BPs are also known to inhibit tumor growths and metastases in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer. METHODS: Two osteosarcoma cell lines (SaOS-2 and U2OS) were treated with risedronate (0, 0.1, 1, 10 microM) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MMP-9 were analyzed by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MMP-9 protein were analyzed by Westernblot, the activities of MMP-2 and MMP-9 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after risedronate treatment. RESULTS: The invasiveness of osteosarcoma cell lines (SaOS-2, U2OS) were reduced in a dose dependent manner follow 48 hour treatment of up to 10 microM of the risedronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MMP-9 were also suppressed by increasing risedronate concentrations. CONCLUSION: Given that MMP-2 and MMP-9 are instrumental in tumor cell invasion, our results suggest the risedronate could reduce osteosarcoma cell invasion.

Polybutylcyanoacrylate nanoparticles as a carrier for mitomycin C in rabbits bearing VX2-liver tumor.

Polybutylcyanoacrylate nanoparticles (PBCA-NP) were prepared by addition of the monomer to an aqueous phase containing dextran 70 and loaded with mitomycin C (MMC-PBCA-NP), a highly effective anticancer drug. When injected into mice, MMC-PBCA-NP accumulated more in the liver than did free MMC. In contrast, MMC-PBCA-NP accumulated less in the heart and kidney than did free MMC. However, when MMC-PBCA-NP and MMC were administered to rabbits bearing VX2 cells implanted into the liver, the antiproliferative effects on the tumor cells of both drugs were similar. Histological analyses indicated that organization of myocardial filaments was disrupted and vacuolization was observed in the MMC treated group, whereas MMC-PBCA-NP treatment did not appear to damage the host's heart. Hydropic degeneration of renal tubular epithelia was observed in the MMC treated group and not in the control group, whereas MMC-PBCA-NP treatment did not appear to damage the host's kidney.

Pharmacological effects of ba-wei-xi-lei powder on ulcerative colitis in rats with enema application.

Ba-wei-xi-lei powder is a classical herbal mixture, and is widely used for the treatment of oral ulcer and ulcerative colitis. This study aimed to explore the effect of Ba-wei-xi-lei powder with enema application on ulcerative colitis in rats. Ulcerative colitis was induced by immunization with rabbit's colonic mucosal protein emulsified with Completely Freund's Adjuvant. The mucosal inflammatory reaction and ulcer have been observed in the model rats. Characteristic changes of ulceractive colitis include that CD4 lymphocyte increased in peripheral blood while CD8 lymphocyte decreased; CD8 lymphocyte and TNF-alpha expression area increased in colonic mucosa, while CD4 lymphocyte decreased. Ba-wei-xi-lei powder and sulfasalazine with enema application could alleviate the pathological changes in the model rats. The results suggest that the pharmacological effects of Ba-wei-xi-lei powder on ulcerative colitis in rats are similar to the effect of sulfasalazine.