Microgel-based carriers enhance skeletal stem cell reprogramming towards immunomodulatory phenotype in osteoarthritic therapy.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1ß and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.

TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

Human osteoarthritic articular cartilage stem cells suppress osteoclasts and improve subchondral bone remodeling in experimental knee osteoarthritis partially by releasing TNFAIP3.

BACKGROUND: Though articular cartilage stem cell (ACSC)-based therapies have been demonstrated to be a promising option in the treatment of diseased joints, the wide variety of cell isolation, the unknown therapeutic targets, and the incomplete understanding of the interactions of ACSCs with diseased microenvironments have limited the applications of ACSCs. METHODS: In this study, the human ACSCs have been isolated from osteoarthritic articular cartilage by advantage of selection of anatomical location, the migratory property of the cells, and the combination of traumatic injury, mechanical stimuli and enzymatic digestion. The protective effects of ACSC infusion into osteoarthritis (OA) rat knees on osteochondral tissues were evaluated using micro-CT and pathological analyses. Moreover, the regulation of ACSCs on osteoarthritic osteoclasts and the underlying mechanisms in vivo and in vitro were explored by RNA-sequencing, pathological analyses and functional gain and loss experiments. The one-way ANOVA was used in multiple group data analysis. RESULTS: The ACSCs showed typical stem cell-like characteristics including colony formation and committed osteo-chondrogenic capacity. In addition, intra-articular injection into knee joints yielded significant improvement on the abnormal subchondral bone remodeling of osteoarthritic rats. Bioinformatic and functional analysis showed that ACSCs suppressed osteoarthritic osteoclasts formation, and inflammatory joint microenvironment augmented the inhibitory effects. Further explorations demonstrated that ACSC-derived tumor necrosis factor alpha-induced protein 3 (TNFAIP3) remarkably contributed to the inhibition on osteoarhtritic osteoclasts and the improvement of abnormal subchondral bone remodeling. CONCLUSION: In summary, we have reported an easy and reproducible human ACSC isolation strategy and revealed their effects on subchondral bone remodeling in OA rats by releasing TNFAIP3 and suppressing osteoclasts in a diseased microenvironment responsive manner.

[An EHG-based Preterm Delivery Prediction Algorithm via Convolution Neural Network].

Premature delivery is one of the direct factors that affect the early development and safety of infants. Its direct clinical manifestation is the change of uterine contraction intensity and frequency. Uterine Electrohysterography(EHG) signal collected from the abdomen of pregnant women can accurately and effectively reflect the uterine contraction, which has higher clinical application value than invasive monitoring technology such as intrauterine pressure catheter. Therefore, the research of fetal preterm birth recognition algorithm based on EHG is particularly important for perinatal fetal monitoring. We proposed a convolution neural network(CNN) based on EHG fetal preterm birth recognition algorithm, and a deep CNN model was constructed by combining the Gramian angular difference field(GADF) with the transfer learning technology. The structure of the model was optimized using the clinical measured term-preterm EHG database. The classification accuracy of 94.38% and F1 value of 97.11% were achieved. The experimental results showed that the model constructed in this paper has a certain auxiliary diagnostic value for clinical prediction of premature delivery.

Psoralen alleviates radiation-induced bone injury by rescuing skeletal stem cell stemness through AKT-mediated upregulation of GSK-3ß and NRF2.

BACKGROUND: Repairing radiation-induced bone injuries remains a significant challenge in the clinic, and few effective medicines are currently available. Psoralen is a principal bioactive component of Cullen corylifolium (L.) Medik and has been reported to have antitumor, anti-inflammatory, and pro-osteogenesis activities. However, less information is available regarding the role of psoralen in the treatment of radiation-induced bone injury. In this study, we explored the modulatory effects of psoralen on skeletal stem cells and their protective effects on radiation-induced bone injuries. METHODS: The protective effects of psoralen on radiation-induced osteoporosis and irradiated bone defects were evaluated by microCT and pathological analysis. In addition, the cell proliferation, osteogenesis, and self-renewal of SSCs were explored. Further, the underlying mechanisms of the protective of psoralen were investigated by using RNA sequencing and functional gain and loss experiments in vitro and in vivo. Statistical significance was analyzed using Student's t test. The one-way ANOVA was used in multiple group data analysis. RESULTS: Here, we demonstrated that psoralen, a natural herbal extract, mitigated radiation-induced bone injury (irradiation-induced osteoporosis and irradiated bone defects) in mice partially by rescuing the stemness of irradiated skeletal stem cells. Mechanistically, psoralen restored the stemness of skeletal stem cells by alleviating the radiation-induced suppression of AKT/GSK-3ß and elevating NRF2 expression in skeletal stem cells. Furthermore, the expression of KEAP1 in skeletal stem cells did not significantly change in the presence of psoralen. Moreover, blockade of NRF2 in vivo partially abolished the promising effects of psoralen in a murine model of irradiation-induced osteoporosis and irradiated bone regeneration. CONCLUSIONS: In summary, our findings identified psoralen as a potential medicine to mitigate bone radiation injury. In addition, skeletal stem cells and AKT-GSK-3ß and NRF2 may thus represent therapeutic targets for treating radiation-induced bone injury.

Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model.

BACKGROUND: The healing of bone defects can be challenging for clinicians to manage, especially after exposure to ionizing radiation. In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing. METHODS: CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed. The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. Moreover, postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis. RESULTS: The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (P < 0.05). Melatonin maintained genomic stability, reduced postradiation CBSC apoptosis and intracellular oxidative stress, and enhanced expression of antioxidant-related enzymes (P < 0.05). Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels via the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. Melatonin was also found to exhibit antioxidant effects via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density values with lower IL-6 and TNF-α levels than in the irradiation and the Matrigel groups (P < 0.05). CONCLUSION: This study suggested that melatonin could protect CBSCs against γ-ray radiation and assist in the healing of postradiation bone defects.

Clinical-grade human dental pulp stem cells suppressed the activation of osteoarthritic macrophages and attenuated cartilaginous damage in a rabbit osteoarthritis model.

BACKGROUND: Although increasing evidence has demonstrated that human dental pulp stem cells (hDPSCs) are efficacious for the clinical treatment of skeletal disorders, the underlying mechanisms remain incompletely understood. Osteoarthritis (OA) is one of the most common degenerative disorders in joints and is characterized by gradual and irreversible cartilaginous tissue damage. Notably, immune factors were newly identified to be closely related to OA development. In this study, we explored the modulatory effects of clinical-grade hDPSCs on osteoarthritic macrophages and their protective effects on cartilaginous tissues in OA joints. METHODS: The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages were explored by phase contrast microscope, transmission electron microscopy, immunostaining, flow cytometry, quantitative polymerase chain reaction, and enzyme linked immunosorbent assay, respectively. Additionally, the factors and signaling pathways that suppressed macrophage activation by hDPSCs were determined by enzyme-linked immunosorbent assay and western-blotting. Furthermore, hDPSCs were administered to a rabbit knee OA model via intra-articular injection. Macrophage activation in vivo and cartilaginous tissue damage were also evaluated by pathological analysis. RESULTS: We found that hDPSCs markedly inhibited osteoarthritic macrophage activation in vitro. The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages changed into less inflammatory status in the presence of hDPSCs. Mechanistically, we observed that hDPSC-derived hepatocyte growth factor and transforming growth factor ß1 mediated the suppressive effects on osteoarthritic macrophages. Moreover, phosphorylation of MAPK pathway proteins contributed to osteoarthritic macrophage activation, and hDPSCs suppressed their activation by partially inactivating those pathways. Most importantly, injected hDPSCs inhibited macrophage activation in osteochondral tissues in a rabbit knee OA model in vivo. Further histological analysis showed that hDPSCs alleviated cartilaginous damage to knee joints. CONCLUSIONS: In summary, our findings reveal a novel function for hDPSCs in suppressing osteoarthritic macrophages and suggest that macrophages are efficient cellular targets of hDPSCs for alleviation of cartilaginous damage in OA. hDPSCs treat OA via an osteoarthritic macrophages-dependent mechanisms. hDPSCs suppress the activation of osteoarthritic macrophages in vitro and in vivo and alleviate cartilaginous lesions in OA models.

Ferulic acid promotes bone defect repair after radiation by maintaining the stemness of skeletal stem cells.

The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a- and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC-mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC-mediated tissue regeneration postradiation.

Biological potential alterations of migratory chondrogenic progenitor cells during knee osteoarthritic progression.

BACKGROUND: Although increasing studies have demonstrated that chondrogenic progenitor cells (CPCs) remain present in human osteoarthritic cartilage, the biological alterations of the CPCs from the less diseased lateral tibial condyle and the more diseased medial condyle of same patient remain to be investigated. METHODS: CPCs were isolated from paired grade 1-2 and grade 3-4 osteoarthritic cartilage by virtue of cell migratory capacities. The cell morphology, immunophenotype, self-renewal, multi-differentiation, and cell migration of these CPCs were evaluated. Additionally, the distributions of CD105+/CD271+ cells in OA osteochondral specimen were determined. Furthermore, a high-throughput mRNA sequencing was performed. RESULTS: Migratory CPCs (mCPCs) robustly outgrew from mildly collagenases-digested osteoarthritic cartilages. The mCPCs from grade 3-4 cartilages (mCPCs, grades 3-4) harbored morphological characteristics, cell proliferation, and colony formation capacity that were similar to those of the mCPCs from the grade 1-2 OA cartilages (mCPCs, grades 1-2). However, the mCPCs (grades 3-4) highly expressed CD271. In addition, the mCPCs (grades 3-4) showed enhanced osteo-adipogenic activities and decreased chondrogenic capacity. Furthermore, the mCPCs (grades 3-4) exhibited stronger cell migration in response to osteoarthritis synovial fluids. More CD105+/CD271+ cells resided in grade 3-4 articular cartilages. Moreover, the results of mRNA sequencing showed that mCPCs (grades 3-4) expressed higher migratory molecules. CONCLUSIONS: Our data suggest that more mCPCs (grades 3-4) migrate to injured articular cartilages but with enhanced osteo-adipogenic and decreased chondrogenic capacity, which might explain the pathological changes of mCPCs during the progression of OA from early to late stages. Thus, these dysfunctional mCPCs might be optional cell targets for OA therapies.

Skeletal stem cell-mediated suppression on inflammatory osteoclastogenesis occurs via concerted action of cell adhesion molecules and osteoprotegerin.

In the current study, we investigated how skeletal stem cells (SSCs) modulate inflammatory osteoclast (OC) formation and bone resorption. Notably, we found that intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and osteoprotegerin (OPG) play a synergistic role in SSC-mediated suppression of inflammatory osteoclastogenesis. The effect of SSCs on inflammatory osteoclastogenesis was investigated using a lipopolysaccharide-induced mouse osteolysis model in vivo and human osteoarthritis synovial fluid (OASF) in vitro. OC formation was determined by tartrate-resistant acid phosphatase staining. Bone resorption was evaluated by microcomputerized tomography, serum C-terminal telopeptide assay, and pit formation assay. The expression of ICAM-1, VCAM-1, and OPG in SSCs and their contribution to the suppression of osteoclastogenesis were determined by flow cytometry or enzyme linked immunosorbent assay. Gene modification, neutralization antibodies, and tumor necrosis factor-α knockout mice were used to further explore the mechanism. The results demonstrated that SSCs remarkably inhibited inflammatory osteoclastogenesis in vivo and in vitro. Mechanistically, inflammatory OASF stimulated ICAM-1 and VCAM-1 expression as well as OPG secretion by SSCs. In addition, ICAM-1 and VCAM-1 recruited CD11b+ OC progenitors to proximity with SSCs, which strengthened the inhibitory effects of SSC-derived OPG on osteoclastogenesis. Furthermore, it was revealed that tumor necrosis factor α is closely involved in the suppressive effects. In summary, SSCs express a higher level of ICAM-1 and VCAM-1 and produce more OPG in inflammatory microenvironments, which are sufficient to inhibit osteoclastogenesis in a "capture and educate" manner. These results may represent a synergistic mechanism to prevent bone erosion during joint inflammation by SSCs.

Effect of medial meniscus extrusion on arthroscopic surgery outcome in the osteoarthritic knee associated with medial meniscus tear: a minimum 4-year follow-up.

BACKGROUND: The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up. METHODS: This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model. RESULTS: Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD -0.630, 95% CI: -1.250, -0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022). CONCLUSIONS: Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.

Intercellular adhesion molecule-1 enhances the therapeutic effects of MSCs in a dextran sulfate sodium-induced colitis models by promoting MSCs homing to murine colons and spleens.

BACKGROUND: To investigate the therapeutic effect of intercellular adhesion molecule (ICAM)-1-modified mesenchymal stem cells (MSCs) in a mouse model of inflammatory bowel disease (IBD) induced by dextran sulfate sodium. METHODS: Primary MSCs and ICAM-1-overexpressing MSCs (C3 cells) were generated in vitro. The IBD mouse model was induced with drinking water containing dextran sulfate sodium for 7 days. For stem cell therapy, mice were randomly assigned to six experimental groups: the control group, IBD group, primary MSC group, C3 group, C3-vector group, and C3-ICAM-1 group. Mice were given a single injection of 1 × 106 primary MSCs or gene-modified MSCs via the tail vein on day 3 of DDS administration. The general conditions of the mice in each group were observed. Additionally, the pathological changes in the colon were observed and scored. Primary MSCs and gene-modified MSCs were stained with the fluorescent dye CM-DIL before injection into the tail vein of mice. The distribution of infused cells in IBD mice was observed in frozen sections. Mechanistically, the polarization of Th1, Th2, Th17, and regulatory T cells (Tregs) in the spleen was determined by flow cytometry. Moreover, the mRNA expression levels of IBD-related immune factors in splenocytes were measured by quantitative PCR. RESULTS: A single injection of MSCs promoted general recovery and reduced pathological damage in IBD mice. Additionally, ICAM-1-overexpressing MSCs had stronger therapeutic effects than ICAM-1low MSCs. Furthermore, the in vivo distribution analysis results indicated that a higher number of ICAM-1-overexpressing MSCs homed to the colon and spleen of IBD mice. Moreover, the delivery of ICAM-1 overexpressing MSCs decreased the numbers of Th1 and Th17 cells but increased the number of Tregs in the spleen of IBD mice. The quantitative PCR analysis results revealed that an infusion of ICAM-1-overexpressing MSCs influenced the expression of spleen-derived immune factors by remarkably reducing the mRNA levels of IFN-γ and IL-17A and increasing the mRNA level of Foxp3. CONCLUSIONS: Our results demonstrate that ICAM-1-modified mesenchymal stem cells (MSCs) remarkably alleviate inflammatory damage in IBD mice by promoting MSC homing to the target and immune organs. The findings suggest that ICAM-1 is required to maintain the therapeutic effects of MSCs in IBD treatment and identified a novel role of ICAM-1 in inflammatory diseases.

Arthroscopy combined with unicondylar knee arthroplasty for treatment of isolated unicompartmental knee arthritis: A long-term comparison.

BACKGROUND: Knee osteoarthritis is the most prevalent form of osteoarthritis and is becoming the main reason for progressive pain in knee joints. Arthroscopy combined with unicondylar knee arthroplasty (UKA) is one of the effective methods for the treatment of severe unicompartmental knee arthritis. This surgical approach gives us the capacity to explore all the articular cavities and plays a vital role in UKA patient selection. However, some scholars think that the surgical procedure is traumatic and may increase the rate of surgical infection, and its clinical efficacy needs further study. AIM: To compare the clinical effect of arthroscopy combined with UKA and UKA alone for patients suffering from unicompartmental osteoarthritis (OA). METHODS: A retrospective study was conducted on patients who were diagnosed with unicompartmental OA (Kellgren-Laurence grade ≥ III) and underwent UKA between October 2012 and November 2006. The patients were followed at 3, 6, and 12 mo and every 2 years thereafter. During each follow-up, the radiographic materials, the range of motion of knee and hospital for special surgery (HSS) score, knee society score and knee function score as recorded, and the modes and time of failure and revision details were collected as well. RESULTS: Data on 104 patients (118 knees), including 54 patients (60 knees) in the arthroscopy combined with UKA group (group A) and 51 (58 knees) in UKA alone group (group B) were collected during an average follow-up duration of 7.25 years, excluding the cases who were lost to follow-up. At the final follow-up, 3 (5.0%) of 60 knees in group A compared with 4 (6.9%) of 58 knees in group B failed and converted to total knee arthroplasty, with no statistically significant difference between the two groups (P = 0.933). The percentage of patients receiving blood transfusion was 40% in group A, significantly lower than that in group B (67.2%; P = 0.003). Total volume of blood transfusion in group A was also significantly lower than that of group B (P = 0.001). Both groups improved significantly after operation in clinical symptoms and functions. HSS score, knee society score, and knee function score increased significantly at the latest follow-up compared to pre-operation in group A, from 59.6 ± 10.9 to 82.7 ± 9.3 (mean difference [MD], 23.2; 95%CI: 19.3-27.0; P = 0.000), 47.3 ± 6.3 to 76.2 ± 13.1 (MD, 28.9; 95%CI: 25.1-32.7; P = 0.000), and 57.5 ± 6.3 to 75.1 ± 19.6 (MD, 17.5; 95% CI: 12.1-23.0; P = 0.000); and in group B, from 59.3 ± 15.6 to 84.3 ± 10.1 (MD, 23.7; 95%CI: 18.9-28.5; P = 0.000), 49.1 ± 9.2 to 75.1 ± 13.2 (MD, 24.7; 95%CI: 19.9-29.5; P = 0.000), and 59.3 ± 9.0 to 77.4 ± 13.8 (MD, 17.2; 95%CI: 12.8-21.6; P = 0.000). CONCLUSION: Arthroscopy combined with UKA and UKA alone both provide benefits in clinical symptom improvement and alignment correction. Arthroscopy combined with UKA does not increase the infection probability and surgical complications, and has an advantage in reducing the total volume of blood transfusion and the percentage of patients receiving blood transfusion.

Chemical composition and antioxidant activities of essential oils from different parts of the oregano.

This research was undertaken in order to characterize the chemical compositions and evaluate the antioxidant activities of essential oils obtained from different parts of the Origanum vulgare L. It is a medicinal plant used in traditional Chinese medicine for the treatment of heat stroke, fever, vomiting, acute gastroenteritis, and respiratory disorders. The chemical compositions of the three essential oils from different parts of the oregano (leaves-flowers, stems, and roots) were identified by gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of each essential oil was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and reducing the power test. Among the essential oils from different parts of the oregano, the leaf-flower oils have the best antioxidant activities, whereas the stem oils are the worst. The results of the DPPH free radical scavenging assay showed that the half maximal inhibitory concentration (IC50) values of the essential oils were (0.332±0.040) mg/ml (leaves-flowers), (0.357±0.031) mg/ml (roots), and (0.501±0.029) mg/ml (stems), respectively. Interestingly, the results of reducing the power test also revealed that when the concentration exceeded 1.25 mg/ml, the leaf-flower oils had the highest reducing power; however, the stem oils were the lowest.

[Current status and expectations in the surgical treatment of recurrent lateral patellar dislocation].

Up to now, surgical treatment of recurrent lateral patellar dislocation mainly includes: medial patellofemoral ligament reconstruction, tibial tubercle osteotomy, trochleoplasty, lateral retinacular release, derotation osteotomy and so on . Clinical reports show that: the use of a single or combined with several methods have achieved ideal short to mid-term clinical outcomes. However, there is no consolidate criterion concerning the choices of different kinds of surgical ways for the treatment of individual recurrent lateral patellar dislocation. Meanwhile, with the wide use of MPFL reconstruction and other surgical options, there are more and more complications and failures that are worthy and necessary for us to pay attention to, even though its high success rate. The aim of this article is to make a systematic review of the application status of different surgical methods, collecting the positive results we have achieved, illuminating application keys of surgical techniques, guiding patient-specific therapy more precisely.

Characterization of the promoter region of the bovine long-chain acyl-CoA synthetase 1 gene: Roles of E2F1, Sp1, KLF15, and E2F4.

The nutritional value and eating qualities of beef are enhanced when the unsaturated fatty acid content of fat is increased. Long-chain acyl-CoA synthetase 1 (ACSL1) plays key roles in fatty acid transport and degradation, as well as lipid synthesis. It has been identified as a plausible functional and positional candidate gene for manipulations of fatty acid composition in bovine skeletal muscle. In the present study, we determined that bovine ACSL1 was highly expressed in subcutaneous adipose tissue and longissimus thoracis. To elucidate the molecular mechanisms involved in bovine ACSL1 regulation, we cloned and characterized the promoter region of ACSL1. Applying 5'-rapid amplification of cDNA end analysis (RACE), we identified multiple transcriptional start sites (TSSs) in its promoter region. Using a series of 5' deletion promoter plasmids in luciferase reporter assays, we found that the proximal minimal promoter of ACSL1 was located within the region -325/-141 relative to the TSS and it was also located in the predicted CpG island. Mutational analysis and electrophoretic mobility shift assays demonstrated that E2F1, Sp1, KLF15 and E2F4 binding to the promoter region drives ACSL1 transcription. Together these interactions integrate and frame a key functional role for ACSL1 in mediating the lipid composition of beef.

[Research progress of anti-drug resistance in traditional Chinese medicine].

Bacterial drug resistance has been always the focus of the world. With the abuse of antibiotics and the emerging of "Superbug" in the world, the harm of drug resistance to human beings is more and more serious, with an uncontrollable trend. Today, with the relative lack of antibiotics, people pay more attention to Chinese herbal medicines with a wide range of sources, high security, less toxic side effects and mysterious anti-drug resistance mechanism, hoping to find new ways or new ideas to solve the problem of drug resistance. In recent years, the screening, extracting and isolating of effective drug resistance inhibitors from natural plants and traditional Chinese Medicine, as well as the investigation in mechanism of anti-drug resistance, have become a hot research in the field of medicine. In this paper, we would analyze and summarize the action mechanism of bacterial drug resistance, characteristics and advantages of anti-drug resistance of traditional Chinese medicine, as well as the herbal ingredients with anti-drug resistance effect, hoping to provide certain theoretical basis and research ideas for solving the problem of bacterial drug resistance and developing new green Chinese antibiotics.

Expression and clinical significance of osteopontin in calcified breast tissue.

Osteopontin (OPN) is an integrin-binding protein, believed to be involved in a variety of physiological cellular functions. The physiology of OPN is best documented in the bone where this secreted adhesive glycoprotein appears to be involved in osteoblast differentiation and bone formation. In our study, we used semi-quantitative RT-PCR of osteopontin in calcification tissue of breast to detect breast cancer metastasis. The obtained data indicate that the expression of osteopontin is related to calcification tissue of breast, and possibly with the incidence of breast cancer. The expression strength of OPN by RT-PCR detection was related to the degree of malignancy of breast lesions, suggesting a close relationship between OPN and breast calcification tissue. The results revealed that expression of OPN mRNA is related to calcification of breast cancer tissue and to the development of breast cancer. Determination of OPN mRNA expression can be expected to be a guide to clinical therapy and prediction of the prognosis of breast cancer patients.