Effect of total knee arthroplasty for valgus knee correction on clinical outcome and patellar position.

PURPOSE: The purpose was to investigate the effect of different degrees of valgus deformity correction on patellar position and clinical outcome in patients with valgus knees after total knee arthroplasty (TKA). METHODS: We retrospectively analyzed and followed 118 patients with valgus knees. Based on the post-operative hip-knee-ankle (HKA), patients were divided into three groups: neutral (±3°), mild (3-6°), and severe (> 6°). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM), and Knee Society Score (KSS) were used to evaluate post-operative clinical efficacy. Also, the patellar tilt angle (ε-angle), congruence angle (θ-angle), and Insall-Salvati index (ISI) were used to represent the patellar position. Post-operative observation indicators included HKA, angle of the femur (α-angle), tibial angle (ß-angle), femoral component flexion angle (γ-angle), and tibial component posterior slope angle (δ-angle). RESULTS: All patients showed significant improvements in HKA, ROM, WOMAC, and KSS after operation (P < 0.001). Regarding patellar position, the ISI values decreased to varying degrees (P < 0.05). The patellar tilt angle was significantly increased in the severe valgus group compared to that in the mild valgus and neutral groups (P < 0.001). Univariate analysis showed that the degree of post-operative residual valgus was significantly affected by WOMAC, KSS, α-, ε-, and θ-angles. CONCLUSION: Minor valgus undercorrection did not affect the short-term outcome after TKA; however, when the residual valgus angle was > 6°, the post-operative scores were significantly reduced. Inadequate valgus correction does not result in significant changes in patellar height but may increase the risk of poor patellar tracking.

MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1.

MicroRNAs have been implicated in drug resistance of osteosarcoma (OS). MicroRNA-301a (miR-301a) is up-regulated and functions as an oncogene in various cancers. However, little is known about the role of miR-301a in drug resistance of OS cells. In this study, we found that doxorubicin induced time-dependent expression of miR-301a in OS cells. Meantime, doxorubicin promoted HMGCR expression and inhibited AMPKα1 expression, which was further facilitated by miR-301a overexpression. Luciferase reporter assay identified AMPKα1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. Consistently, our data showed that miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS compared to those in control OS. Our findings suggested that miR-301a might be a potential biomarker for chemotherapy-resistant OS and a promising therapeutic target for overcoming drug resistance of OS.

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1.

Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.

Folic Acid and Taurine Alleviate the Impairment of Redox Status, Immunity, Rumen Microbial Composition and Fermentation of Lambs under Heat Stress.

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

Population genetics of swamp eel in the Yangtze River: comparative analyses between mitochondrial and microsatellite data provide novel insights.

The swamp eel (Monopterus albus) is a typical sex reversal fish with high economic value. Several phylogeographic studies have been performed using various markers but comparative research between mitochondrial and nuclear markers is rare. Here, a fine-scale study was performed across six sites along the Yangtze River including three sites on the main stem and three sites from tributaries. A total of 180 swamp eel individuals were collected. Genetic structure and demographic history were explored using data from two mitochondrial genes and eight microsatellite loci. The results revealed the samples from tributary sites formed three separate clades which contained site-specific lineages. Geographic isolation and the habitat patchiness caused by seasonal cutoff were inferred to be the reasons for this differentiation. Strong gene flow was detected among the sites along the main stem. Rapid flow of the river main stem may provide the dynamic for the migration of swamp eel. Interestingly, the comparative analyses between the two marker types was discordant. Mitochondrial results suggested samples from three tributary sites were highly differentiated. However, microsatellite analyses indicated the tributary samples were moderately differentiated. We conclude this discordance is mainly caused by the unique life history of sex reversal fish. Our study provides novel insights regarding the population genetics of sex reversal fish.

Tai chi chuan exercises improve functional outcomes and quality of life in patients with primary total knee arthroplasty due to knee osteoarthritis.

BACKGROUND AND PURPOSE: Postoperative rehabilitation plays an indispensable role for a successful total knee arthroplasty (TKA) and the optimal exercises programs are not known. A single-centre, single-blind, randomised controlled trial was designed to explore whether tai chi chuan (TCC) exercises can improve the functional outcomes and the quality of life (QOL) in patients with primary TKA due to knee osteoarthritis (OA). MATERIALS AND METHODS: One hundred seven participants with primary TKA for end-stage knee OA were enrolled from January 2014 to January 2017. Patients were treated for 12 weeks either with TCC exercises (intervention) or traditional physical exercises (control). Outcomes including western ontario and mcMaster universities arthritis index (WOMAC), 6-min walk test (6 MWT), knee range of motion (ROM), and short form (36) health survey (SF-36) were assessed. The adverse events related to TCC exercises or TKA were recorded. RESULTS: Before the intervention, the two groups were comparable after examining the general descriptions of patients. Compared with the control group (CG), the TCC group (TG) had significantly better scores in the WOMAC physical function score, 6 MWT, SF-36 physical component score (PCS), and the mental component score (MCS) (P < 0.05) after the 12-week intervention. Nevertheless, there were no significant differences in WOMAC pain score and knee ROM. There were no adverse events related to the TCC exercise program. In the CG, three patients reported one fall each, but those falls did not lead to a further problem. CONCLUSION: The TCC exercises improve the physical function and the QOL in patients with primary TKA without additional risks.

The complete mitochondrial genome of Acrossocheilus wenchowensis (Cyprinidae, Barbinae) from Xinanjiang River.

The complete mt genome sequence of Acrossocheilus wenchowensis was obtained by PCR, containing 37 genes with 13 protein coding genes, 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and a non-coding control region.

Mitochondrial DNA sequence of the hybrid of Pelteobagrus vachelli (♀) × Pelteobagrus fulvidraco (♂).

The complete mitochondrial genome sequence of a hybrid, which was produced by sexual hybridization of Pelteobagrus vachelli (♀) × Pelteobagrus fulvidraco (♂), was obtained. The complete mitochondrial genome of the hybrid is 16,532 bp, containing 37 genes. 129 Site differences were found in overall length compared with P. vachelli.

WITHDRAWN: Long non-coding RNA HOTAIR promotes LPS-induced inflammatory injury by down-regulation of microRNA-124 in murine chondrogenic ATDC5 cells.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Dehydroeffusol inhibits viability and epithelial-mesenchymal transition through the Hedgehog and Akt/mTOR signaling pathways in neuroblastoma cells.

Neuroblastoma (NB) is the most predominant extracranial solid tumor of infancy in the world. However, current chemotherapy has limited efficacy for more advanced stages of NB due to acquired chemoresistance or acute toxicity in NB patients. Therefore, effective novel anti-NB drugs are desperately needed. The present study aimed to investigate the effects of dehydroeffusol (DHE), a phenanthrene isolated from J. effuses, on NB cells and its underlying mechanism. The results showed that DHE treatment effectively inhibited NB cell viability in a dose-dependent manner. Moreover, DHE treatment suppressed the epithelial-mesenchymal transition (EMT) process in NB cells by promoting the expression of E-cadherin (E-cad) and restraining the expressions of N-cadherin (N-cad) and vimentin. Also, the invasive capacity and expression of MMP-2 and MMP-9 in NB cells were inhibited by DHE. Furthermore, DHE suppressed the hedgehog (Hh) and the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in NB cells. In conclusion, DHE effectively inhibited the viability and EMT through inactivating the Hh and the Akt/mTOR signaling pathways in NB cells, providing a novel evidence that DHE may be a potential anti-NB drug candidate.

The study of sclareol in inhibiting proliferation of osteosarcoma cells by apoptotic induction and loss of mitochondrial membrane potential.

Sclareol (sclarcol) is an organic compound extracted from sage clary plants. Recent study has showed its anti-tumor effects against breast cancer, gastric carcinoma, osteosarcoma and colorectal cancer. However, its exact mechanisms in inhibiting tumor growth remain unknown. This study thus observed the effect of sclareol on the proliferation of osteosarcoma cells, in an attempt to investigate the role of sclarcol on osteosarcoma growth. MG63 osteosarcoma cell was treated with different concentrations of sclarcol. CCK8 assay was used to test its effect on cell proliferation. LC50 value was then determined to obtain optimal treatment dose. MG63 cells were then divided into control and drug treated group, for measuring apoptosis and mitochondrial membrane potential by flow cytometry, and the expression of cytochrome c, Bax and Bcl-2 by western blot. CCK8 analysis showed that sclareol inhibited MG63 cell proliferation, with an LC50 value at 11.0 µM. Flow cytometry results showed the apoptotic cell ratio was 13.8%, 24.1% and 37.3% after treated with 2.0 µM, 4.0 µM and 8.0 µM sclareol respectively. Compared to control group, sclareol significantly depressed mitochondrial membrane potential of MG63 cells, increased the expression of cytochrome c and Bax, but decreased Bcl-2 expression. In conclusion, Sclareol can inhibit the proliferation of MG63 cells, and induce cell apoptosis and decrease mitochondrial membrane potential suggesting the inhibition of osteosarcoma cells by sclareol might be via both apoptosis induction and decreasing mitochondrial membrane potential.

Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression.

The present study aimed to investigate the role of the soluble programmed death­1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. Expression of sPD­1 in Treg was detected by western blot analysis. Immunosuppressive activity of CD4+CD25­ Treg was measured via thiazolyl blue in an MTT assay. ELISA was used to detect interleukin­10 (IL­10), transforming growth factor beta (TGF-ß), interleukin-4 (IL-4), interferon­Î³ (IFN-γ) and nuclear factor of activated T cells (NF­AT). It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD­1 levels were markedly higher (P<0.001), compared with the HC group. Additionally, it was observed that relative sPD­1 protein expression in the small interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25­ T group, optical density (OD)540 values, IFN-γ/IL-4 concentration ratio and NF­AT activity in siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 value, IFN-γ/IL-4 concentration ratio and NF­AT activity in the siRNA­sPD­1 group were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the level of CD4+CD25­ Tregs in the peripheral blood of RA patients, and may be involved in a variety of immune processes mediated by CD4+CD25­ Tregs.