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BackgroundOsteosarcoma is an aggressive malignant tumor which has attracted worldwide attention. MEX3A may be associated with tumors while has not yet seen its coverage on osteosarcoma. Herein, this study was to investigate the correlation between MEX3A and the progression of osteosarcoma.MethodsFirstly, we determined that expression of MEX3A was significantly higher in osteosarcoma tissues than that in marginal bone by immunohistochemical staining. Additionally, MEX3A expression was downregulated by the RNAi‐mediated knockdown. The functions of MEX3A knockdown on proliferation, apoptosis, cell cycle, migration was assessed by MTT assay, flow cytometry, wound-healing assay and Transwell assay, respectively. Knockdown of MEX3A resulted in suppressing cell proliferation, increasing cell apoptosis, inducing the G2 phase cell cycle arrest, and attenuating cellular migration. Furthermore, mouse xenograft model confirmed inhibitory effects of MEX3A knockdown on osteosarcoma formation.ResultsThe preliminary exploration on the molecular mechanism of MEX3A in osteosarcoma cells showed that the induction of apoptosis needs the participation of a series of apoptosis- associated factors, such as upregulation of Caspase 3, Caspase 8 and HSP60, downregulation of HSP27 and XIAP.ConclusionsIn summary, these findings predicated that therapy directed at decreasing MEX3A expression is a potential osteosarcoma treatment.

Neurofibromatosis type I is a common genetic disease that can lead to disfigurement, neurological and functional disorders. However, it is rare to meet the case which a huge mass is formed rapidly after neurofibroma ruptures. This case report describes a rare case of a 52-year-old female with a rapidly expanding mass on her back and mild anemia as the main symptoms. Physical examination showed a huge mass on the back and a surface ulceration with the diameter of 6 cm. Imaging examination revealed the abundant blood supply to the lesion. We performed preoperative arterial embolization, and surgical resection on the fifth day after embolization. After operation, proper blood transfusion and vacuum sealing drainage (VSD) were given. Through 9-months follow-up study, the incision of the patient recovered well and there was no sign of tumor recurrence. Therefore, this case report provides clinicians with valuable experience in the treatment for rapidly expanding neurofibroma.

Osteoarthritis (OA) is a common degenerative disease that affects the vast majority of the elderly and may eventually embark on the road of the total knee arthroplasty (TKA), although controversy still exists in the medical community about the best therapies for osteoarthritis. Compared with physical therapy, oral analgesics and other non-operative treatments, intra-articular injection is more safe and effective. Moreover, intra-articular injection is much less invasive and has fewer adverse reactions than surgical treatment. This article reviews mechanism, benefits and adverse reactions of corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), mesenchymal stem cell (MSCs), stromal vascular fraction (SVF) and other new therapies (for example: gene therapy). The application prospect of intra-articular injection was analyzed according to the recent progress in drug research.

Background Our study aimed to explore more mechanistic insights into the epigenetic regulation of osteoarthritis (OA). Methods The expression profiles (accession number: GSE64393 and GSE64394) were downloaded from the Gene Expression Omnibus database. The differentially hydroxymethylated regions (DhMRs) and differentially expressed genes (DEGs) between OA and control groups were identified. The distribution of DhMRs in the whole genome and the correlation between DhMRs and DEGs were analyzed. Functional module mining for the DEGs and DhMRs was conducted, followed by protein–protein interaction (PPI) analysis. The transcriptional factor (TF) was predicted. Results Total 52,282 DhMRs were obtained, among which 31,452 ones were annotated to 9726 genes. Additionally, 1806 DEGs were selected. Hydroxymethylation mainly occurred in gene body region. Correlation analysis revealed that more than 70% of DhMRs were uncorrelated with DEGs expression. Functional module mining for the DEGs and DhMRs identified 2 functional modules, which were involved in pathways of regulation of actin cytoskeleton, and TGF-β signaling pathway. A PPI network was constructed, and ITGB3 had the highest degree. Furthermore, 7 TFs were predicted, which regulated 12 candidate genes, such as HES1-PTEN. Conclusions The onset and progression of OA may be associated with the upregulated hydroxymethylation in gene body region of PTEN. HES1 may be important TF in the pathogenesis of OA. Additionally, pathways of regulation of actin cytoskeleton, and TGF-beta signaling pathway may also play important roles in OA progression.

Surface chemistry and mechanical stability determine the osteogenic capability of bone implants. The development of high-strength bioactive scaffolds for in-situ repair of large bone defects is challenging because of the lack of satisfying biomaterials. In this study, highly bioactive Ca-silicate (CSi) bioceramic scaffolds were fabricated by additive manufacturing and then modified for pore-wall reinforcement. Pure CSi scaffolds were fabricated using a direct ink writing technique, and the pore-wall was modified with 0%, 6%, or 10% Mg-doped CSi slurry (CSi, CSi-Mg6, or CSi-Mg10) through electrostatic interaction. Modified CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds with over 60% porosity demonstrated an appreciable compressive strength beyond 20 MPa, which was ~2-fold higher than that of pure CSi scaffolds. CSi-Mg6 and CSi-Mg10 coating layers were specifically favorable for retarding bio-dissolution and mechanical decay of scaffolds in vitro. In-vivo investigation of critical-size femoral bone defects repair revealed that CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds displayed limited biodegradation, accelerated new bone ingrowth (4-12 weeks), and elicited a suitable mechanical response. In contrast, CSi scaffolds exhibited fast biodegradation and retarded new bone regeneration after 8 weeks. Thus, tailoring of the chemical composition of pore-wall struts of CSi scaffolds is beneficial for enhancing the biomechanical properties and bone repair efficacy.

Background Von-Hippel Lindau (VHL) disease is rare neurocutaneous disorder arising from an inactivating mutation of the VHL gene on chromosome 3p35. The disease is inherited in an autosomal dominant fashion and predominantly involves tissues originating from the ectodermal germ layer. Although hemangioblastomas of retina and cerebellum are the most common clinical features, multiple-organ involvement in the form of renal cell carcinomas, spinal hemangioblastomas, renal cysts, and pancreatic cysts have also been reported. Hemangioblastomas of the spinal canal could present as cauda equina syndrome. Case Description We describe the case of a 55-year-old man with cauda equina syndrome as his first manifestation. An initial magnetic resonance imaging scan uncovered hemangiomas in the spinal canal. A thorough family history strongly suggested an autosomal dominant pattern of disease inheritance. Further physical examination and imaging revealed additional organ involvement consistent with VHL. We performed laminectomy and partial resection of hemangioblastoma for decompression. He recovered satisfactorily with his cauda equina syndrome resolving quickly post operation. No deterioration was apparent by the 12-month follow-up visit. Conclusions To the best of our knowledge, this is the first case with cauda equina syndrome as the first manifestation of VHL disease. Laminectomy and partial resection of hemangioblastoma are safe and effective treatments to resolve impingement of the spinal cord. VHL disease resulting in hemangioblastoma in the spinal canal is rarely seen but should be included in the differential diagnosis of cauda equina syndrome to facilitate genetic counseling for the proband and offspring.

Bone osteogenic sarcoma has a poor prognosis, as the exact cell of origin and the signaling pathways underlying tumor formation remain undefined. Here, we report an osteogenic tumor mouse model based on the conditional knockout of liver kinase b1 (Lkb1, also known as Stk11) in Cathepsin K–Cre–expressing (Ctsk-Cre–expressing) cells. Lineage-tracing studies demonstrated that Ctsk-Cre could label a population of periosteal cells. The cells functioned as mesenchymal progenitors with regard to markers and functional properties. LKB1 deficiency increased proliferation and osteoblast differentiation of Ctsk+ periosteal cells, while downregulation of mTORC1 activity, using a Raptor genetic mouse model or mTORC1 inhibitor treatment, ameliorated tumor progression of Ctsk-Cre Lkb1fllfl mice. Xenograft mouse models using human osteosarcoma cell lines also demonstrated that LKB1 deficiency promoted tumor formation, while mTOR inhibition suppressed xenograft tumor growth. In summary, we identified periosteum-derived Ctsk-Cre–expressing cells as a cell of origin for osteogenic tumor and suggested the LKB1/mTORC1 pathway as a promising target for treatment of osteogenic tumor.

Background Extranodal natural killer (NK) / T cell lymphoma is a subtype of non-Hodgkin's lymphoma (NHL) that usually has an aggressive clinical course. It is the predominant trigger of lymphoma-associated hemophagocytic syndrome (LAHS), which is highly lethal and with extremely poor prognosis. This study is aiming to characterize the associated clinical features and prognostic factors of the disease. Patients and methods Twenty-eight patients with extranodal NK/T cell lymphoma associated hemophagocytic lymphohistiocytosis (HLH) were retrospectively analyzed. The clinical records were collected, and the associations between clinical or laboratory parameters and overall survival (OS) were assessed. Results The most frequently clinical characteristics were fever (96.4%), and splenomegaly (81.5%). Concerning the laboratory findings, the most common features were hyperferritinemia (91.7%), grade III/IV thrombocytopenia (64.3%), hypertriglyceridemia (48%), severe anemia (46.4%), hypofibrinogenemia (45%), and grade III/IV neutropenia (32.1%). The interval between the diagnosis of NK/T LAHS and death / last contact was between 4 to 701 days with the median interval of 15 days. We found that higher serum lactic dehydrogenase (LDH) at HLH, hypofibrinogenemia, and splenomegaly were significantly associated with worse survival (P=0.002, 0.003, 0.003). Furthermore, Eastern Cooperative Oncology Group (ECOG) score, extra-upper aerodigestive tract NK/T cell lymphoma (EUNKTL) and cutaneous involvement were risk factors of HLH. Conclusion Our data indicated that levels of LDH, fibrinogen, and presence of splenomegaly were prognostic factors of the disease. Higher ECOG scores, EUNKTL and cutaneous involvement were risk factors of NK/T LAHS. Additional independent, prospective clinical trials will be needed to explore optimal treatment.

Background: Multiple osteochondromas (MO) are an autosomal-dominant disease characterized by the growth of multiple cartilage-capped prominences in the growth plate region of the metaphysis in long and flat bones. Materials and Methods: To detect genetic mutations related to MO, a three-generation Chinese family with MO was evaluated using whole exome sequencing for mutation screening. The candidate pathogenic mutation was validated by Sanger sequencing. Results: A novel frameshift (NM_000401.3:c.1321del:p.Leu441TrpfsTer28) in exon 8 of the exotosin 2 (EXT2) gene was identified in two affected individuals. Codons 441 and 468 in the EXT2 gene are highly conserved among vertebrates as demonstrated by multiple sequence alignment. The c.1321 del C resulted in an amino acid change at codon 441, which generated a premature stop codon at position 468, causing complete loss of the glycosyltransferase domain. Conclusions: A novel frameshift mutation c.1321delC detected in the EXT2 gene may help in prenatal genetic screening and early diagnosis of MO.

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

The major limitations of clinical outcome predictions of osteomyelitis mediated by Staphylococcus aureus (S. aureus) are not specific and definitive. To this end, current studies aim to investigate host immune responses of trend changes of Iron-regulated surface determinant (Isd) of IsdA, IsdB, IsdH, cell wall-modifying proteins of amidase (Amd) and glucosaminidase (Gmd), and secreted virulence factor of chemotaxis inhibitory protein S. aureus (CHIPS) and staphylococcal complement inhibitor (SCIN) longitudinally to discover their correlationship with clinical outcomes. 55 patients with confirmed S. aureus infection of the long bone by clinical and laboratory methods were recruited for the study. Whole blood was collected at 0-, 6-, 12- month for serum that was used to test IsdA, IsdB, IsdH, Gmd, Amd, CHIPS and SCIN using a customized Luminex assay after clinical standard care parameters were collected. The patients were then divided into two groups: 1) infection controlled vs. 2) adverse outcome based on clinical criteria for statistical analysis. We found that standard clinical parameters were unable to distinguish therapeutic outcomes. Significant over-expression of all antigens was confirmed in infection patients at 0-, 6-, 12- month time points. A distinct expression trend and dynamic changes of IsdB, Amd, Gmd, and CHIPS were observed between infection controlled and. adverse outcome patients, while the IsdA, IsdH, SCIN remained demonstrated no statistical significance. We conclude that dynamic changes of specific antigens could predict clinical outcomes of S. aureus osteomyelitis. Clinical Relevance: The trend changes of host immune responses to S. aureus specific antigens of IsdB, Gmd, Amd, and CHIPS could predict clinical outcomes of S. aureus osteomyelitis. This article is protected by copyright. All rights reserved.

Rationale: Intraspinal tophaceous gout is relatively rare condition presenting with major clinical manifestations, such as spinal cord or nerve roots compressions (radiculopathy). It is usually difficult to differentiate intraspinal tophaceous gout, lumbar disc herniation, stenosis of spinal canal, ossification of ligamentum flavum, and other degenerative spinal disorders from each other. Patient concerns: A 64-year-old man was admitted with a history of progressive low back pain for 11 months. He also presented with radiculopathy and numbness of his left lower extremity. Diagnoses: Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) showed L4/5 disc herniation and lateral recess stenosis on the left side. During the operation of percutaneous transforaminal endoscopic decompression, intraspinal chalky white material was seen. Post-operative pathologic results confirmed the diagnosis of gouty tophi. Interventions: Percutaneous transforaminal endoscopic decompression was performed as treatment. Intraspinal chalky white material was seen. We removed most of the chalky white material and extruded nucleus. Outcomes: His symptom subsided rapidly and no deterioration was noted 1 year post-operatively. Lessons: Although intraspinal tophaceous gout is not commonly seen, clinicians should take it into consideration as a possible differential diagnosis when the patient exhibits axial pain or neurological deficits with risk factors of gout. We identified and treated this case with percutaneous transforaminal endoscopic decompression for the first time and got an excellent outcome. Percutaneous transforaminal endoscopic surgery proved to be an effective and minimally invasive alternative for identifying and treating intraspinal tophaceous gout.

Long non-coding RNAs (lncRNAs) are involved in the occurrence and progression of numerous types of cancer. The aim of the present study was to evaluate the effect of the lncRNA maternally expressed gene 3 (MEG3) on the migration and invasion of non-small cell lung cancer (NSCLC) H1299 and PC9 cells. Reverse transcription-quantitative (RT-q)PCR analysis showed that MEG3 was downregulated in NSCLC PC9 and H1299 cells. Additionally, bioinformatics analysis indicated that MEG3 sponges microRNA (miR)-21-5p; miR-21-5p was predicted to target the phosphatase and tensin homolog (PTEN) 3′-untranslated region sequence. MEG3 overexpression led to miR-21-5p suppression and PTEN upregulation in PC9 and H1299 cells, as detected by RT-qPCR. Subsequently, western blot analysis confirmed that MEG3 overexpression enhanced PTEN expression levels and inhibited the PI3K/AKT signaling pathway in NSCLC cells. These effects were attenuated by miR-21-5p. Dual luciferase assay supported the sponging effect of MEG3 on miR-21-5p and validated the direct interaction between miR-21-5p and PTEN. Furthermore, Transwell assay demonstrated that MEG3 overexpression had an inhibitory effect on cell migration and invasion. MEG3 overexpression also mediated epithelial-to-mesenchymal transition by significantly enhancing E-cadherin and decreasing N-cadherin, Vimentin and matrix metalloprotein 9 expression levels in NSCLC cells, as indicated by western blot analysis. These changes were partially reversed by an miR-21-5p mimic. These results indicated that MEG3 acted as a tumor suppressor that inhibited NSCLC cell migration and invasion via sponging miR-21-5p, which, in turn, enhanced the expression levels of PTEN, in part via the PI3K/AKT signaling pathway. The results of the present study have suggested the potential of MEG3 as a novel therapeutic target for NSCLC treatment.

Osteoarthritis (OA) is one of the most prevalent joint disorders globally. Patients suffering from OA are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose‑derived stem cells (ADSCs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient‑derived primary cells. First, it was tested whether patient‑derived ADSCs could differentiate into chondrogenic and osteogenic lineages. The ADSCs were then used as a source of exosomes. It was found that exosomes isolated from ADSCs, when co‑cultured with activated synovial fibroblasts, downregulated the expression of pro‑inflammatory markers interleukin (IL)‑6, NF‑κB and tumor necrosis factor‑α, while they upregulated the expression of the anti‑inflammatory cytokine IL‑10; without exosomes, the opposite observations were made. In addition, inflammation‑inflicted oxidative stress was induced in vitro by stimulating chondrocytes with H2O2. Treatment with exosomes protected articular chondrocytes from H2O2‑induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including Collagen type II and β‑catenin; inhibition of Wnt/β‑catenin, using the antagonist ICG‑001, prevented exosome‑induced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microRNA (miR)‑145 and miR‑221. The upregulation of miR‑145 and miR‑221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patient‑derived exosomes, produced from ADSCs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.

Introduction Oxidative stress is the main cause of osteoarthritis (OA). Lycium barbarum polysaccharides (LBP) have antioxidant properties. Thus, the potential effect of LBP on H2O2-stimulated chondrocytes was examined. Material and methods The cell viability was detected by CCK-8. The reactive oxygen species (ROS) production and apoptosis rates were determined by flow cytometric analysis. The DNA damage was detected by comet assay. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to examine the expression of histone 2A family member X (γH2AX), checkpoint kinase 1 (Chk1), poly ADP-ribose polymerase (PARP), cysteinyl aspartate specific proteinase (caspase)-3/8/9, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its antioxidant-response element (ARE) dependent factors including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1). Results Compared to the H2O2 group, LBP inhibited the ROS production and DNA damage caused by H2O2 (p < 0.05), respectively. LBP inhibited the mRNA and protein expressions of γH2AX and Chk1 (p < 0.05). Meanwhile, LBP significantly decreased apoptosis (p < 0.05). And LBP inhibited the expression levels of PARP and Caspase-3/8/9 (p < 0.05). Moreover, LBP increased the expression of Nrf2, HO-1and NQO-1 (p < 0.05). Furthermore, the depletion of Nrf2 that mediated by RNA interference reversed the apoptosis and DNA damage inhibition effect of LBP (p < 0.05). Conclusions LBP protected chondrocytes through inhibiting DNA damage and apoptosis caused by H2O2, in which the Nrf2/ARE signaling pathway played a positive role. It provided an inspiration for clinical application - developing LBP as a therapeutic agent and Nrf2 as a promising candidate.

Treatment of a type II tibial eminence avulsion fracture was controversial. The aim of this study was to compare the clinical outcomes of a modified arthroscopic suture fixation versus conservative immobilization in treatment of this type fracture in immature population. A total of 43 type II avulsion fractures of tibial intercondylar eminence in immature patients were retrospectively enrolled in the study. Twenty-two (13 males, 9 females) were treated with arthroscopic suture fixation and 21(12 males, 9 females) with conservative cast immobilization. Radiograph, Lachman test, anterior drawer test (ADT), International Knee Documentation Committee (IKDC) 2000 subjective score, and Lysholm score were used to evaluate clinical outcomes in follow-up. All 43 paediatric or adolescent patients with a mean of 11.3 years (range, 8–16 years) were followed up for a median period of 34.5 months (range, 24–46 months). Radiographic evaluation showed optimal reduction immediately after surgery and bone union within three months. At the final follow-up, no limitation of knee motion range was found in any children. Grade II laxity was found in one case from surgical group and six from conservation group, showing significant difference based on ADT (χ2 = 7.927, P = 0.005) and Lachman tests (χ2 = 9.546, P = 0.002). IKDC and Lysholm scores were significantly improved; however, there were significant differences in the IKDC score (91.7 ± 4.34 vs. 84.7 ± 6.11, t = 4.35, P

Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown.In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed.We demonstrated that tricarboxylic acid (TCA) cycle is activated while antigen presentation is repressed in patients with CDK5 overexpression and poor survival. This results indicated that sufficient energy production and tumor immune escape are important characteristics and potential therapeutic targets for this subgroup of osteosarcoma patients. Furthermore, several critical hub genes that are associated with CDK5 related osteosarcoma progression such as MELK were identified.This study discussed the pro-malignant role of CDK5 and potential mechanisms involved. Further preclinical and clinical studies to develop CDK5 based treatments are warranted.

Heterotopic ossification (HO) is pathological bone formation characterized by ossification within muscle, tendons, or other soft tissues. However, the cells of origin and mechanisms involved in the pathogenesis of HO remain elusive. Here we show that deletion of suppressor of fused (Sufu) in cathepsin K–Cre–expressing (Ctsk-Cre–expressing) cells resulted in spontaneous and progressive ligament, tendon, and periarticular ossification. Lineage tracing studies and cell functional analysis demonstrated that Ctsk-Cre could label a subpopulation of tendon-derived progenitor cells (TDPCs) marked by the tendon marker Scleraxis (Scx). Ctsk(+)Scx(+) TDPCs are enriched for tendon stem cell markers and show the highest self-renewal capacity and differentiation potential. Sufu deficiency caused enhanced chondrogenic and osteogenic differentiation of Ctsk-Cre–expressing tendon-derived cells via upregulation of Hedgehog (Hh) signaling. Furthermore, pharmacological intervention in Hh signaling using JQ1 suppressed the development of HO. Thus, our results show that Ctsk-Cre labels a subpopulation of TDPCs contributing to HO and that their cell-fate changes are driven by activation of Hh signaling.

Purpose To compare the time return to work and long-term results of tendoscopic versus open technique for de Quervain’s disease. Methods From 2005 to 2013, either tendoscopic or open decompression was performed on 56 consecutive patients (56 wrists) with symptomatic de Quervain’s disease despite a minimum of 3 months non-operative treatment. Of the 50 patients who met the inclusion criteria, 41 patients were followed-up for a mean of 7.21 years postoperatively. Among these 41 wrists, 20 underwent tendoscopic release (group A), and 21 underwent open release (group B). The clinical evaluations were performed preoperatively, 1 month postoperatively and at last follow-up visit, using visual analog scale (VAS); the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome score; and the Finkelstein’s test. The Patient and Observer Scar Assessment Scale (POSAS) was used as an esthetic evaluation tool of the scar at last follow-up. Results No significant baseline differences were found between two groups. The average time return to work in group A was less than in group B (P P P P P Conclusions The results of this study suggest that tendoscopic technique for de Quervain’s disease could provide earlier symptom relief and earlier recovery with fewer complications and more desirable scar, as well as equivalent successful long-term outcome, when compared with traditional open release technique.

The aim of the present study was to investigate the associations between single nucleotide polymorphisms (SNPs) in the PDZ and LIM domain protein 4 (PDLIM4) gene and susceptibility to osteoporotic fracture in an elderly Han Chinese population. Seven SNPs of PDLIM4, including rs77584624, rs78418541, rs270611, rs3900945, rs77486529, rs71583465, and rs366512, were examined in 540 elderly Chinese patients with osteoporotic fractures (case group) and 540 healthy Chinese subjects (control group) using Sanger sequencing. A-allele carriers of rs270611 in PDLIM4 had a significantly high risk of osteoporotic fracture (adjusted odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.24–1.46; P

BACKGROUND This study compared the efficacy of combined lateral and medial approach, lateral approach, and anterior medial approach in treatment of terrible triad of the elbow (TTE). MATERIAL AND METHODS Thirty-eight TTE patients hospitalized in our center were retrospectively analyzed, among which 14 patients were arranged for combined lateral and medial approach, 12 for lateral approach, and 12 for anterior medial approach. All included patients underwent open reduction, collateral ligament repair, and postoperative function exercise. Follow-up was conducted for 13~22 months. The elbow motion, excellent and good rate, healing time, and complication rate were recorded and compared. RESULTS These 3 approaches significantly improved the postoperative elbow motion, MEPS, VAS, excellent and good rate, and open reduction (all P

A 23-year-old male patient presented with multiple large masses in his elbows, buttocks, knees, Achilles tendons, feet, shoulders and hands. The large masses in the elbows and buttocks measured ~6×5×5 cm and ~7×5×4 cm, respectively. The patient presented with an elevated level of low-density lipoprotein cholesterol, and had been previously diagnosed with homozygous familial hypercholesterolemia (FH) and multiple xanthomas. Local surgical excisions were performed to remove the massive xanthomas from the elbows and buttocks, and histological analysis of the surgical specimens confirmed the previous diagnosis of homozygous FH (HoFH). The aim of the present study was to report a rare case of HoFH coinciding with multiple, large and widely-distributed xanthomas and to discuss the clinical characteristics, in order to provide a better understanding of xanthomas and FH.

Background: The optimal surgical treatment of delayed avulsion fractures of the posterior cruciate ligament (PCL) is still controversial. Purpose: To evaluate the clinical results of arthroscopic suture fixation of tibial avulsion fractures of the PCL with autograft augmentation reconstruction. Study Design: Case series; Level of evidence, 4. Methods: From January 2013 to February 2017, we treated 15 patients with delayed tibial avulsion fractures of the PCL arthroscopically through posteromedial and posterolateral portals. The PCL and avulsion bone fragment were fixed with No. 2 nonabsorbable FiberWire sutures that were pulled out through a single tibial bone tunnel and fixed on a small Endobutton. Concomitantly, anatomic PCL augmentation reconstruction was performed, and the graft was pulled out through the same tunnel and fixed with an interference screw. Knee stability was assessed using the posterior drawer test, and the side-to-side difference was determined using a KT-1000 arthrometer with 134 N of posterior force at 30° of knee flexion. The International Knee Documentation Committee (IKDC) 2000 subjective form and Lysholm scale were used to evaluate clinical outcomes at follow-up. Overall, 12 patients were enrolled for analysis. The mean follow-up period was 34.4 months (range, 26-49 months). Results: At the final follow-up, 2 patients encountered 10° terminal flexion limitations. All patients had negative posterior drawer test results. The KT-1000 arthrometer side-to-side difference was significantly decreased from 8.25 ± 1.96 mm preoperatively to 1.08 ± 0.86 mm at the last follow-up ( P < .001). The mean IKDC and Lysholm scores, respectively, increased from 54.67 ± 7.13 and 53.50 ± 7.90 preoperatively to 91.13 ± 3.78 and 94.25 ± 3.32 at the final follow-up ( P < .001 for both). Conclusion: Arthroscopic suture fixation with autograft augmentation reconstruction for delayed tibial avulsion fractures of the PCL showed good clinical stability and function in this study.

Background Yin-deficiency-heat (YDH) syndrome is a subhealth state of the individual, mainly manifested as oral ulcers, dry mouth, constipation, and other symptoms. Zhibai Dihuang granule (ZDG), as a classic traditional Chinese medicine, is effective in treating YDH syndrome. We screened the potential biomarkers for diagnosing YDH syndrome, and explored the mechanisms of the therapeutic effect of ZDG. Methods Plasma samples from the Pinghe (PH, healthy control) group, the Shanghuo (SH, YDH syndrome) group, and the ZDG treated group (therapeutic group) were analyzed by using metabolomics profiling. The data were analyzed by multivariate statistical and bioinformatics analyses. Results We screened four differential metabolites such as, decanoylcarnitine, dodecanoylcarnitine, phosphatidylcholine (PC), and Aspartate (Asp) Arginine (Arg) Proline (Pro) in the SH group and the PH group. The results showed that the combination of above four metabolites could serve as a potential biomarker for the early diagnosis of YDH syndrome. The metabolites decanoylcarnitine and glucose were found to be differentially expressed in the YDH syndrome group and tended to be normalized after ZDG treatment. Conclusion The increased levels of four differential metabolites (decanoylcarnitine, dodecanoylcarnitine, PC, and Asp Arg Pro) revealed that individuals with YDH syndrome may have increased energy metabolism in the body, which could lead to disorders of fatty acids β-oxidation and immune function. The levels of two differential metabolites including decanoylcarnitine and glucose returned to normal after ZDG treatment, indicating that ZDG could treat YDH syndrome by regulating glucose metabolism and fatty acids β-oxidation. Our study provides a new method for the diagnosis of YDH syndrome, and may provide theoretical basis for novel therapeutic strategies of YDH syndrome.

Multiple exostoses (MO), also referred to as hereditary multiple exostoses (HME), is an autosomal dominant inherited skeletal disorder that has been found to be associated with mutations in the EXT1 and EXT2 genes. In the present study, we report a Chinese family with HME and our mutational analyses of the EXT1 and EXT2 genes in affected and unaffected individuals.All exons of the EXT1 and EXT2 genes in seven family members were polymerase chain reaction amplified from blood and sequenced.A heterozygous mutation (c.1056GT) was identified in exon 2 of the EXT1 gene in the proband and other affected family members; this mutation was not found in the unaffected family members.This c.1056GT mutation is located in the exostosin domain of the EXT1 protein and leads to an amino acid change of Glutamine (Gln) to Histidine (His) at position 352. Homology searches reveal that Gln352 is highly conserved in many species and may play an essential role in the normal function of the EXT1 protein.This study contributes to a better understanding of the genetic basis of HME, expands the known mutational spectrum of EXT1, and provides a reference for genetic counseling and prenatal diagnosis of this family.

The purpose of this study was to compare the clinical and radiological efficacy of autologous adipose-derived stromal vascular fraction (SVF) versus hyaluronic acid in patients with bilateral knee osteoarthritis. Sixteen patients with bilateral symptomatic knee osteoarthritis (K-L grade II to III; initial pain evaluated at four or greater on a ten-point VAS score) were enrolled in this study, which were randomized into two groups. Each patient received 4-ml autologous adipose-derived SVF treatment (group test, n = 16) in one side of knee joints and a single dose of 4-ml hyaluronic acid treatment (group control, n = 16) in the other side. The clinical evaluations were performed pre-operatively and post-operatively at one month, three months, six months, and 12-months follow-up visit, using the ten-point visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the knee range of motion (ROM). The whole-organ assessment of the knees was performed with whole-organ magnetic resonance imaging score (WORMS) based on MRI at baseline, six months and 12-months follow-up. The articular repair tissue was assessed quantitatively and qualitatively by magnetic resonance observation of cartilage repair tissue (MOCART) score based on follow-up MRI at six months and 12 months. No significant baseline differences were found between two groups. Safety was confirmed with no severe adverse events observed during 12-months follow-up. The SVF-treated knees showed significantly improvement in the mean VAS, WOMAC scores, and ROM at 12-months follow-up visit compared with the baseline. In contrast, the mean VAS, WOMAC scores, and ROM of the control group became even worse but not significant from baseline to the last follow-up visit. WORMS and MOCART measurements revealed a significant improvement of articular cartilage repair in SVF-treated knees compared with hyaluronic acid-treated knees. The results of this study suggest that autologous adipose-derived SVF treatment is safe and can effectively relief pain, improve function, and repair cartilage defects in patients with knee osteoarthritis.

The purpose of this study was to introduce a modified arthroscopic treatment technique for popliteal cyst and hypothesize that this modified technique would provide good clinical efficacy and low recurrence rate. From January 2013 to January 2017, 34 patients with symptomatic popliteal cysts were treated with our technique. A figure-of-four position and double posteromedial portals were used to achieve adequate enlargement of the posteromedial valvular opening between the cyst and the joint cavity and complete excision of the cyst wall. MRI was used to detect the recurrence of the popliteal cyst, and the Rauschning and Lindgren score was recorded to evaluate the clinical outcome. All patients were followed up with a mean period of 14.8 months (range, 12 to 36 months). Associated intra-articular lesions were found and treated in all cases. Degenerative cartilage damage was the most common pathology, which affected 23 (67.6%) of the cases. The Rauschning and Lindgren score improved significantly after surgery, and no evidence of recurrence was found from MRI in any case. Our modified arthroscopic treatment technique, using a figure-of-four position and double posteromedial portals, is effective and safe for treating popliteal cyst.

// Ji-Feng Xu 2, 3 , Ya-Ping Wang 1 , Shui-Jun Zhang 2 , Yu Chen 2 , Hai-Feng Gu 2 , Xiao-Fan Dou 2 , Bing Xia 2 , Qing Bi 2 and Shun-Wu Fan 3 1 Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang 310009, P.R. China 2 Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China 3 Department of Orthopedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China Correspondence to: Shun-Wu Fan, email: fansw@srrsh.com Keywords: osteosarcoma (OS), chemotherapy sensitivity, exosome, microRNA, poor chemotherapeutic response Received: January 12, 2017 Accepted: April 15, 2017 Published: June 06, 2017 ABSTRACT A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p

Procyanidins have lipolysis effect on adipose metabolism, but the underlying mechanism is not fully understood. The aim of present study was to examine the effect of grape seed procyanidin B2 (GSP) on the adipogenic differentiation of 3T3-L1 preadipocyte cell line and investigate the underlying mechanism. The results showed that GSP treatment significantly reduced the intracellular lipid accumulation in induced 3T3-L1 cells by targeting miR-483-5p as well as peroxisome proliferator-activated receptor γ (PPARγ). In addition, our results revealed that overexpression of miR-483-5p increased adipogenic differentiation, while inhibition of miR-483-5p reduced the lipid accumulation by suppressing the adipogenic differentiation. Moreover, overexpression of miR-483-5p could reverse GSP's inhibition of adipocyte differentiation as well as increase the level of PPARγ. These results demonstrate that GSP inhibits adipogenesis by targeting PPARγ and suggest this effect might be mediated by miR-483-5p.

Purpose: To: 1) assess the correlation between CT vascularity and a candidate molecular marker of RCC metastasis (insulin-like mRNA binding protein-3 (IMP3)); and 2) demonstrate the differential expression of IMP3 in high vs. low vascular tumors. Experimental design: Retrospectively obtained contrast CT from 72 patients with primary RCC were used to establish threshold values for Low, Intermediate and High tumor vascularity. Paired histopathology specimens from 33 of these patients were used for immunohistochemistry (IHC) to correlate CT with IMP-3 expression. IMP-3 gene expression studies were performed on RCC and poorly vascular prostate cancer (PC) human bone metastases samples to confirm presence of IMP3 in metastatic samples from RCC. Gene expression studies were performed on RCC 786-O and PC3 cell lines to confirm the presence of high expression of IMP3 in the RCC cell line. Results: IMP-3 expression positively correlated with CT vascular enhancement (p