Gangyong Huang

CXCL12–CXCR4 contributes to the implication of bone marrow in cancer metastasis

The CXCL12-CXCR4 axis is postulated to be a key pathway in the interaction between (cancer) stem cells and their surrounding supportive cells in the (cancer) stem cell niche. As the bone marrow constitutes a unique microenvironment for cancer cells, the CXCL12-CXCR4 axis assists the bone marrow in regulating cancer progression. This interaction can be disrupted by CXCR4 antagonists, and this concept is being used clinically to harvest hematopoietic stem/progenitor cells from the bone marrow. The functions of CXCL12-CXCR4 axis in cancer cell-tumor microenvironment interaction and angiogenesis have been recently studied. This review focuses on how CXCL12-CXCR4 helps the bone marrow in creating a tumor mircoenvironment that results in the cancer metastasis. It also discusses ongoing research regarding the clinical feasibility of CXCR4 inhibitors.

Computer navigation and total knee arthroplasty.

Research has added evidence in favor of computer-navigated techniques over conventional surgery for total knee arthroplasty (TKA). The goal of the current meta-analysis was to compare the outcome of outliers in mechanical axis and postoperative complications in patients undergoing conventional vs computer-navigated techniques for TKA. English literature searches were performed in PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published between January 2002 and August 2012. Randomized, controlled trials comparing computer navigation with conventional surgery for the measurement of mechanical axes in patients with primary osteoarthritis were considered eligible. Fifteen trials were eligible for inclusion. The baseline demographics of 2089 patients (computer-navigated=1111; conventional=978) were well matched. Publication bias was eliminated using the funnel plot. A mechanical axis of more than 30° was considered to be malalignment and an outlier in limb alignment. A significant increase of 16.9 minutes in mean operative time for computer-navigated TKA was observed (P=.046). Although patients undergoing computer-navigated TKA had fewer outliers in mechanical axis (13.4%) compared with the conventional technique (27.4%), the results did not achieve statistical significance (I2=0.0%; P=1.000). Fewer complications were observed in patients undergoing computer-navigated TKA (4%) compared with conventional TKA (6.5%).

Effect of the knee position during wound closure after total knee arthroplasty on early knee function recovery

ObjectiveThis study investigated the effect of the knee position during wound closure on early knee function recovery after total knee arthroplasty (TKA).MethodsThis study included 80 primary total knee arthroplasties due to osteoarthritis. The patients were randomized according to the type of wound closure: extension group for full extension and flexion group for 90° flexion. The incision of articular capsule was marked for precise wound alignment. In the flexion group, the knee was kept in high flexion for 1 to 2 min after wound closure. The two groups were treated with the same postoperative rehabilitation exercises. The range of motion (ROM), visual analogue scale (VAS) score of anterior knee pain, Knee Society Score (KSS) and postoperative complications were assessed at 6 weeks, 3 months and 6 months, postoperatively.ResultsAt 6 weeks and 3 months postoperatively, the ROM in flexion group was 98.95 ± 10.33° and 110.05 ± 4.93° respectively, with 87.62 ± 8.92° and 95.62 ± 6.51° in extension group, respectively; The VAS score of anterior knee pain in flexion group was 2.02 ± 1.38 and 2.21 ± 0.87, respectively, with 2.57 ± 1.07 and 2.87 ± 0.83 in extension group, respectively. The ROM and VAS pain score of the two groups were significantly different at these two time points, with no significant difference at 6 months postoperatively. The two groups were not significantly different in KSS, and no apparent complication was observed at three time points.ConclusionMarking the articular capsule incision, wound closure in flexion and high flexion after wound closure can effectively decrease anterior knee pain after TKA and promote the early recovery of ROM.

HDAC5 promotes osteosarcoma progression by upregulation of Twist 1 expression

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we firstly investigated the biological function of HDAC5 in osteosarcoma cells. We found that mRNA and protein levels of HDAC5 were upregulated in osteosarcoma tissues and cell lines. Furthermore, overexpression of HDAC5 could promote cell proliferation in osteosarcoma cell lines. In contrast, HDAC5 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been reported as an oncogene. Together, these results highlighted for the first time an unrecognized link between HDAC5 and osteosarcoma progression and demonstrated that its specific inhibition might contribute to the treatment of tumorigenesis.

Three-dimensional virtual reality simulation of periarticular tumors using Dextroscope reconstruction and simulated surgery: a preliminary 10-case study.

BACKGROUND Dextroscope® three-dimensional (3D) imaging has been extensively used to generate virtual reality (VR) workspaces for neurosurgery and laparoscopy, but few applications have been reported for orthopedic surgery. Here, we investigated orthopedic periarticular tumor surgery planning and anatomical characteristics using a Dextroscope. MATERIAL AND METHODS Patients undergoing surgery for periarticular tumors (n=10) between October 2008 and June 2010 were enrolled and presurgically subjected to computed tomography (CT), magnetic resonance imaging (MRI), and MRI angiography (MRI-A). Imaging data were transferred and integrated in a Dextroscope to produce a VR simulation. The presurgical 3D anatomical reconstructions and intraoperative anatomical characteristics (virtual vs. actual data) and surgical approach (virtual vs. actual situation) measurement and subjective appearance were compared. RESULTS Anatomical characteristics in the area of interest and tumor diameters in all 3 planes (superior-inferior, medial-lateral, and anteroposterior) were consistent between virtual and actual data (3.92±1.22, 1.96±0.53, and 1.73±0.44 vs. 3.92±1.13, 1.91±0.44, and 1.81±0.41; P=0.99, 0.24, and 0.09, respectively). However, the virtual surgical situations were inconsistent with the actual intraoperative situation in many cases, leading to complications. The resolutions of the original CT, MRI, and MRI-A images directly correlated with 3D simulation quality, with soft tissues most poorly represented. Tumor tissue imaging quality in 3D varied extensively by tumor type. CONCLUSIONS Anatomical structures of periarticular tumors can be reconstructed using the Dextroscope system with good accuracy in the case of simple fenestration, increasing treatment individualization, surgical competence level, and potentially reducing intraoperative complications. However, further specialization of VR tools for use in orthopedic applications that involve specialized tools and procedures, such as drilling and implant placement, are urgently need.

Microarray‑based screening of differentially expressed genes in glucocorticoid‑induced avascular necrosis

The underlying mechanisms of glucocorticoid (GC)-induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC-induced ANFH. E-MEXP-2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid-induced ANFH rats compared with 5 placebo-treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC-induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25-Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α-2-macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC-induced ANFH via interacting with VDR. A2M may also be involved in the development of GC-induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC-induced ANFH may provide novel targets for diagnostics and therapeutic treatment.

Total knee arthroplasty using trochlear groove as guide for position of femoral component in severe knee osteoarthritis

BackgroundApart from transepicondylar axis, the native femoral sulcus was also reported to be used as a guide for the femoral component position in total knee arthroplasty (TKA). However, it was not shown in patients with severe knee osteoarthritis. This study was conducted to compare the position of trochlear groove in patients with and without osteoarthritis, and to assess whether trochlear groove could be used as a guide for position of femoral component in TKA for severe knee osteoarthritis.MethodsTotal 50 severe knee osteoarthritis patients (Kellgren Lawrence grade 3 or 4) who underwent TKA were included. Meanwhile, 50 patients who underwent arthroscopic surgery without osteoarthritis were included as control. The distance from trochlear groove to the midpoint of a virtual anterior condyle osteotomy line (parallel to the posterior condyle line) (a–b) was recorded by radiological and surgical measurements. Midpoint of transepicondylar axis and trochlear groove were used as guide for placing prosthesis model in TKA, respectively. No-thumb test was performed to assess the patellar tracking. The position of femoral component was finally performed using trochlear groove as guide in TKA.ResultsValue of “a–b” was significantly different between osteoarthritic and control knees (P = 0.008). During the placement of prosthesis model, similar patellar tracking was detected between using midpoint of transepicondylar axis and trochlear groove as guide (P > 0.05). After placing femoral component using trochlear groove as guide, most patients obtained good patellofemoral congruence with pneumatic tourniquet inflated (n = 43) or deflated (n = 5), and good patellofemoral congruence was also obtained by lateral patellar retinaculum release in two patients.ConclusionDespite the shifting of trochlear groove caused by severe knee osteoarthritis, trochlear groove can be used as a guide for position of femoral component, with equivalent patellar tracking compared with transepicondylar axis.

Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

BackgroundThe purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors.MethodsA total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed.ResultsTreated cases included 15 patients aged 29 ±7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 ±12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 ±4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence.ConclusionsThe procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities.

Radius neck-to-humerus trochlea transposition elbow reconstruction after proximal ulnar metastatic tumor resection: case and literature review.

Wide en bloc excision of proximal ulna sections is used to treat traumatic and pathological fractures of the ulna, though poor standardization of clinical treatment often results in long-term failure of such reconstructed biomechanical structures. In order to provide insight into effective ulnar reconstructive treatments, the case of an 80-year-old Chinese Han male presenting with pathological fracture caused by a proximal ulnar metastatic tumor concurrent with metastatic renal cancer complicated by occurrence in the brain and lungs is reported and contrasted with alternative treatment techniques. Wide resectioning of the proximal ulna and reconstruction with local radius neck-to-humerus trochlea transposition resulted in preservation of functionality, sensitivity, and biomechanical integrity after postsurgical immobilization, 6 weeks of passive- and active-assisted flexion, and extension with a hinged brace. The resultant Musculoskeletal Tumor Society rating score was 25 of 30 (83 %). Full sensitivity and mobility of the left hand and elbow (10° to 90° with minimally impaired supination and pronation) was restored with minimal discomfort. No evidence of local recurrence or other pathological complications were observed within a 1-year follow-up period. Efficient reconstruction of osseous and capsuloligamentous structures in the elbow is often accomplished by allografts, prosthesis, and soft tissue reconstruction, though wide variations in risk and prognosis associated with these techniques has resulted in disagreements regarding the most effective standards for clinical treatment. Current findings suggest that radius neck-to-humerus trochlea transposition offers a superior range of elbow movement and fewer complications than similar allograft and prosthetic techniques for patients with multiple metastatic cancers.

FGF2 and FAM201A affect the development of osteonecrosis of the femoral head after femoral neck fracture

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease associated with high disability, and femoral neck fracture (FNF) is one of the most common reasons for traumatic ONFH. This study was designed to reveal the mechanisms underlying ONFH. Using fastx_toolkit and prinseq-lite tools, quality control was conducted for the sequencing data. The differentially expressed genes (DEGs, including both mRNAs and lncRNAs) between ONFH and FNF samples were identified using the edgeR package in R, and were then subjected to enrichment analysis using the BioCloud platform. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape software. After the target genes of DE-lncRNAs were predicted based on Spearmans rank correlation coefficient, lncRNA-gene coexpression network was visualized using the Cytoscape software. Furthermore, functional enrichment analysis was carried out for the target genes using the clusterprofiler package in R. Additionally, the key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2965 DEGs were identified from the ONFH samples, including 602 DE-lncRNAs (such as downregulated FAM201A). In the PPI networks, eight upregulated genes (including FGF2, IGF1, SOX9, and COL2A1) and 11 downregulated genes were among the top 20 genes according to all of the scores, such as degree centrality, closeness centrality, and betweenness centrality scores. Functional enrichment analysis showed that IGF1, SOX9, and COL2A1 were significantly enriched during skeletal system development. Moreover, qRT-PCR experiments detected the upregulation of FGF2 and downregulation of FAM201A in ONFH samples. FGF2 and FAM201A were correlated with the development of ONFH. Besides, IGF1, SOX9, and COL2A1 might also affect the pathogenesis of ONFH.