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1.
Redox Biol ; 64: 102767, 2023 08.
Article in English | MEDLINE | ID: mdl-37290302

ABSTRACT

BACKGROUND: Necroptosis and pyroptosis, two types of proinflammatory programmed cell death, were recently found to play important roles in spinal cord injury (SCI). Moreover, cyclic helix B peptide (CHBP) was designed to maintain erythropoietin (EPO) activity and protect tissue against the adverse effects of EPO. However, the protective mechanism of CHBP following SCI is still unknown. This research explored the necroptosis- and pyroptosis-related mechanism underlying the neuroprotective effect of CHBP after SCI. METHODS: Gene Expression Omnibus (GEO) datasets and RNA sequencing were used to identify the molecular mechanisms of CHBP for SCI. A mouse model of contusion SCI was constructed, and HE staining, Nissl staining, Masson staining, footprint analysis and the Basso Mouse Scale (BMS) were applied for histological and behavioural analyses. qPCR, Western blot analysis, immunoprecipitation and immunofluorescence were utilized to analyse the levels of necroptosis, pyroptosis, autophagy and molecules associated with the AMPK signalling pathway. RESULTS: The results revealed that CHBP significantly improved functional restoration, elevated autophagy, suppressed pyroptosis, and mitigated necroptosis after SCI. 3-Methyladenine (3-MA), an autophagy inhibitor, attenuated these beneficial effects of CHBP. Furthermore, CHBP-triggered elevation of autophagy was mediated by the dephosphorylation and nuclear translocation of TFEB, and this effect was due to stimulation of the AMPK-FOXO3a-SPK2-CARM1 and AMPK-mTOR signalling pathways. CONCLUSION: CHBP acts as a powerful regulator of autophagy that improves functional recovery by alleviating proinflammatory cell death after SCI and thus might be a prospective therapeutic agent for clinical application.


Subject(s)
Peptides, Cyclic , Spinal Cord Injuries , Mice , Animals , Peptides, Cyclic/pharmacology , Peptides, Cyclic/therapeutic use , AMP-Activated Protein Kinases/metabolism , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism , Apoptosis , Signal Transduction , Autophagy
2.
Oxid Med Cell Longev ; 2021: 8186877, 2021.
Article in English | MEDLINE | ID: mdl-34712387

ABSTRACT

Spinal cord injury (SCI) refers to a major worldwide cause of accidental death and disability. However, the complexity of the pathophysiological mechanism can result in less-effective clinical treatment. Growth differentiation factor 11 (GDF-11), an antiageing factor, was reported to affect the development of neurogenesis and exert a neuroprotective effect after cerebral ischaemic injury. The present work is aimed at investigating the influence of GDF-11 on functional recovery following SCI, in addition to the potential mechanisms involved. We employed a mouse model of spinal cord contusion injury and assessed functional outcomes via the Basso Mouse Scale and footprint analysis following SCI. Using western blot assays and immunofluorescence, we analysed the levels of pyroptosis, autophagy, necroptosis, and molecules related to the AMPK-TRPML1-calcineurin signalling pathway. The results showed that GDF-11 noticeably optimized function-related recovery, increased autophagy, inhibited pyroptosis, and alleviated necroptosis following SCI. Furthermore, the conducive influences exerted by GDF-11 were reversed with the application of 3-methyladenine (3MA), an autophagy suppressor, indicating that autophagy critically impacted the therapeutically related benefits of GDF-11 on recovery after SCI. In the mechanistic study described herein, GDF-11 stimulated autophagy improvement and subsequently inhibited pyroptosis and necroptosis, which were suggested to be mediated by TFE3; this effect resulted from the activity of TFE3 through the AMPK-TRPML1-calcineurin signalling cascade. Together, GDF-11 protects the injured spinal cord by suppressing pyroptosis and necroptosis via TFE3-mediated autophagy augmentation and is a potential agent for SCI therapy.


Subject(s)
Autophagy/drug effects , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Growth Differentiation Factors/pharmacology , Necroptosis/drug effects , Pyroptosis/drug effects , Spinal Cord Injuries/drug therapy , Spinal Cord/drug effects , AMP-Activated Protein Kinases/metabolism , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Calcineurin/metabolism , Disease Models, Animal , Female , Mice, Inbred C57BL , Recovery of Function , Signal Transduction , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord/physiopathology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Transient Receptor Potential Channels/metabolism
3.
J Orthop Surg Res ; 16(1): 41, 2021 Jan 11.
Article in English | MEDLINE | ID: mdl-33430913

ABSTRACT

BACKGROUND: Anterior-posterior compression (APC) type II pelvis fracture is caused by the destruction of pelvic ligaments. This study aims to explore ligaments injury in APC type II pelvic injury. METHOD: Fourteen human cadaveric pelvis samples with sacrospinous ligament (SPL), sacrotuberous ligament (SBL), anterior sacroiliac ligament (ASL), and partial bone retaining unilaterally were acquired for this study. They were randomly divided into hemipelvis restricted and unrestricted groups. We recorded the separation distance of the pubic symphysis and anterior sacroiliac joint, external rotation angle, and force when ASL ruptured. We observed the external rotation damage to the pelvic bone and ligaments. RESULT: When ASL failed, there was no significant difference in pubic symphysis separation (28.6 ± 8.4 mm to 23.6 ± 8.2 mm, P = 0.11) and anterior sacroiliac joint separation (11.4 ± 3.8 mm to 9.7 ± 3.9 mm, P = 0.30) between restricted and unrestricted groups. The external rotation angle (33.9 ± 5.5° to 48.9 ± 5.2°, P < 0.01) and force (553.9 ± 82.6 N to 756.6 ± 41.4 N, P < 0.01) were significantly different. Pubic symphysis separation between two groups ranged from 14 to 40 mm. In the restricted group, both SBL and SPL were injured. SPL ruptured first, and then SBL and the interosseous sacroiliac ligament were damaged while the posterior ligament remained unharmed. In the unrestricted group, interosseous sacroiliac ligament and posterior sacroiliac ligaments were damaged, while SBL and SPL were not. When the ASL, SBL, and SPL all failed, pubic symphysis and anterior sacroiliac joint separation between two groups increased significantly (from 28.6 ± 8.4 to 42.0 ± 7.6 mm, 11.4 ± 3.8 to 16.7 ± 4.2 mm respectively, all P < 0.05). CONCLUSION: Pelvic external rotation injury is either hemipelvic restricted or unrestricted, which can result in different outcomes. When the ASL ruptures, the unrestricted group needs greater external rotation angle and force, without SBL or SPL injury, while both SBL and SPL were injured in another group. When ASL fails in two groups, pubic symphysis separation fluctuates considerably. Finally, when the ASL ruptures, SBL and SPL may be undamaged.


Subject(s)
Fractures, Compression/etiology , Fractures, Compression/physiopathology , Ligaments/injuries , Pelvic Bones/injuries , Adult , Biomechanical Phenomena , Cadaver , Female , Humans , Ligaments/physiopathology , Male , Middle Aged , Rupture
4.
Z Gerontol Geriatr ; 53(2): 163-170, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31950363

ABSTRACT

Osteoporotic bones heal more slowly and ineffectively than normal bones. A combination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1-34 (PTH 1-34) may improve healing. A standard osteoporotic rat model was established 12 weeks after bilateral ovarian resection (OVX). Bone defects were created in the right femora of 80 rats, which were randomly divided into 4 groups: control, Scl-Ab (25 mg/kg twice weekly), PTH (60 µg/kg of PTH 1-34 three times a week) and PTH plus Scl-Ab. After 12 weeks of treatment the rats were sacrificed and blood and the distal femora were harvested for biochemical evaluation, histology, microcomputed tomography and biomechanical testing. Compared to the control group, monotherapy and combination therapy with PTH and/or Scl-Ab promoted the formation of new bone, enhanced maximum femoral loading and increased the levels of procollagen type I N­terminal propeptide (PINP) and osteocalcin. The administration of PTH + Scl-Ab maximally enhanced bone defect healing. Combination treatment was better than either treatment alone, indicating a synergistic effect.


Subject(s)
Antibodies/administration & dosage , Bone Morphogenetic Proteins/immunology , Bone Remodeling/physiology , Fracture Healing/drug effects , Parathyroid Hormone/therapeutic use , Animals , Bone Density/drug effects , Bony Callus/drug effects , Disease Models, Animal , Drug Therapy, Combination , Female , Humans , Ovariectomy , Parathyroid Hormone/pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , X-Ray Microtomography/methods
5.
Cell Biochem Funct ; 38(4): 460-471, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31960487

ABSTRACT

Osteoarthritis (OA), the most common chronic joint disease in the elderly, has become a significant economic burden for families and societies worldwide. Although treatments are continually improving, current drugs only target joint pain, with no effective therapies modifying OA progression. Long noncoding RNAs (lncRNAs), which have received increasing attention in recent years, are abnormally expressed in OA cartilage. In the present study, weighted coexpression network analysis (WGCNA) was applied to identify modules related to certain OA clinical traits. In total, 4404 coding genes and 161 lncRNAs were differentially expressed based on two OA expression profile data sets and normal control samples. Subsequently, 11 independent modules were acquired, and the green module, with a total of 49 hub genes, was identified as the most relevant to OA. These hub genes were validated using the GSE12021 data set. There was only one lncRNA among the hub genes, namely, NONHSAG034351. Thus, we further explored the function of NONHSAG034351-related genes in the network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that NONHSAG034351-associated genes are involved in the response to lipopolysaccharide, angiogenesis, tumour necrosis factor (TNF) signalling, and mitogen-activated protein kinase (MAPK) signalling pathways. In conclusion, we identified modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub-lncRNA, was downregulated in OA synovial tissue and might play a significant role in the pathological progression of this disease. Our findings have important clinical implications and could provide novel biomarkers that indicate the molecular mechanisms of OA and act as potential therapeutic targets. SIGNIFICANCE OF THIS STUDY: Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in osteoarthritis (OA), which is the most common chronic joint disease among the elderly. In the present study, we report the expression profiles of lncRNAs in OA and the identification of modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub-lncRNA identified to be downregulated in the synovial tissue of OA patients, might play a significant role in the pathological progression of OA. Furthermore, our findings provide novel biomarkers associated with the molecular mechanisms underlying OA pathogenesis, thus implying potential therapeutic targets with important clinical implications.


Subject(s)
Osteoarthritis/metabolism , RNA, Long Noncoding/metabolism , Synovial Membrane/metabolism , Transcriptome , Biomarkers/metabolism , Humans , Osteoarthritis/genetics , RNA, Long Noncoding/genetics
6.
J Cell Physiol ; 234(12): 22477-22484, 2019 12.
Article in English | MEDLINE | ID: mdl-31119756

ABSTRACT

CD4+ T cells differentiated into Th17 cells are a main cause for occurrence and development of rheumatoid arthritis (RA). This study aims to define the role of long noncoding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) and its downstream molecule in Th17 cell differentiation. Determination of lncRNA NEAT1 expression in the peripheral blood mononuclear cells (PBMCs) of patients with RA and in Th17 cells induced differentiation in vitro used quantitative real-time polymerase chain reaction. Lentivirus-constructed short hairpin RNA interference for NEAT1 (Lenti-siRNA-NEAT1) was pretransfected into CD4+ T cells before inducing treatment of Th17 cell differentiation. NEAT1 targets STAT3 protein was proved by RNA pull down. Lenti-siRNA-NEAT1 was injected into the joint of the mice arthritis model to verify the function of NEAT1 knockdown. Our results showed that NEAT1 is significantly upregulated in the PBMCs of RA patients, as well as in Th17 cells in vitro induced from CD4+ T cells. The knockdown of NEAT1 restrains CD4+ T cells differentiate into Th17 cells. STAT3 protein, a critical molecule for Th17 cell differentiation, is a downstream molecule for NEAT and its cellular level can be positively targeted and regulated by NEAT via reducing the ubiquitination level. Moreover, the cotreatment of NEAT1 knockdown and STAT3 overexpression promotes Th17 cell differentiation compared with NEAT1 knockdown alone. Knockdown of Th17 by in vivo injection of lenti-siRNA-NEAT1 relieves arthritis degree in II type collagen induced mice arthritis model. These data concluded that NEAT1 is auxo-active molecule for CD4+ T cells differentiating into Th17 cells and knockdown of NEAT1 positively inhibits Th17/CD4+ T cell differentiation through reducing the STAT3 protein level.


Subject(s)
CD4-Positive T-Lymphocytes/physiology , RNA, Long Noncoding/metabolism , STAT3 Transcription Factor/metabolism , Animals , Arthritis, Experimental , Arthritis, Rheumatoid/metabolism , Cell Differentiation , Flow Cytometry , Gene Expression Regulation , Gene Knockdown Techniques , Humans , Male , Membrane Proteins , Mice , Mice, Inbred DBA , RNA, Long Noncoding/genetics , STAT3 Transcription Factor/genetics , T-Lymphocytes, Regulatory , Th17 Cells
7.
Int Orthop ; 43(9): 2141-2149, 2019 09.
Article in English | MEDLINE | ID: mdl-30903254

ABSTRACT

PURPOSE: Displaced intra-articular calcaneus fractures Sanders type IV(DIACFS IV) can result in an unsatisfactory prognosis and a high complication rate. Our investigation intends to compare the outcomes of DIACFS IV treated by open reduction and internal fixation (ORIF) via sinus tarsi approach (STA) with these via extensile lateral approach (ELA). METHODS: Sixty-nine patients (82 ft) with DIACFS IV who were treated with ORIF (29 in STA group and 40 in ELA group) were retrospectively assessed. Median follow-up was 50 months in two groups. Radiographic results were reviewed pre-operatively and post-operatively, and relative complications were collected. Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analog scale (VAS). RESULTS: The wound-healing complication rate was 14.28% in STA group and 34.04% in ELA group (p = .043), and overall complication rate was 54% and 77% (p = .056), respectively. Seven cases of sural nerve injury only occurred in ELA group. The post-operative radiographs of the calcaneus (Böhler's angle, height, width, and length) were significantly different from those measured pre-operatively in each group. And these data were parallel between the two groups. In STA and ELA groups, the average AOFAS was 75.45 versus 72.44 (p = .496), and the mean VAS was 23.95 versus 30.93 (p = .088), respectively. CONCLUSION: Similar clinical and radiographic outcomes are achieved between STA and ELA. And STA has a lower incidence of wound healing complication and sural nerve injury. Therefore, ORIF via STA can be a considerable management for DIACFS IV.


Subject(s)
Calcaneus/injuries , Calcaneus/surgery , Foot Injuries/surgery , Fracture Fixation, Internal/methods , Intra-Articular Fractures/surgery , Adult , Calcaneus/diagnostic imaging , Female , Foot Injuries/diagnostic imaging , Fracture Fixation, Internal/adverse effects , Humans , Intra-Articular Fractures/classification , Intra-Articular Fractures/diagnostic imaging , Male , Middle Aged , Open Fracture Reduction/methods , Prognosis , Retrospective Studies , Young Adult
8.
Am J Transl Res ; 11(1): 379-392, 2019.
Article in English | MEDLINE | ID: mdl-30787995

ABSTRACT

Random-pattern skin flap transplantation is a common procedure in plastic surgery, but its distal area usually incurs ischemia and necrosis. Resveratrol (Rev), a natural polyphenol primarily found in peanuts, grapes, and red wine, which exerts multi-bioactivity. In this study, forty-eight rats with the modified "McFarlane flap" model were divided into Control and Rev groups, which were treated with vehicle Control and Rev, respectively. After 7 days of continuous treatment and observation, ischemic flap tissues were harvested to evaluate angiogenesis, apoptosis, oxidative stress, and autophagy. It was observed a greater survival area of flaps, accompanied with reduced water content and stronger blood supply, in the Rev group than in the Control group. In addition, Rev upregulated the expression of MMP9, VEGF, and Cadherin5, indicating that Rev promotes angiogenesis in ischemic flaps. Moreover, Rev decreased the levels of Bax, CYC, and Caspase3, suggesting that it inhibits apoptosis. Besides, Rev increased the expression of SOD1, eNOS, HO1, the activities of SOD and GSH, and reduced the levels of MDA, which uncovers that it depresses oxidative stress in ischemic flaps. Finally, it increased the expression of Beclin1, LC3II, VPS34, and CTSD, and decreased SQSTM1/p62 levels, which reveals that it activates autophagy in the flaps. These results suggest that Rev promotes random skin flap survival through proangiogenic, antiapoptotic, and antioxidative effects; moreover, autophagy is activated in the process, which might be another underlying mechanism for the flap survival.

9.
J Orthop Surg Res ; 13(1): 321, 2018 Dec 17.
Article in English | MEDLINE | ID: mdl-30558614

ABSTRACT

BACKGROUND: Wound infections after posterior spinal surgery are a troublesome complication; patients are occasionally forced to remove the internal fixation device, which can lead to instability of the spine and injury to the spinal cord. The purpose of this study was to evaluate the efficacy of modified vacuum-assisted closure (VAC) for treating an early postoperative spinal wound infection. METHODS: We conducted a retrospective study of 18 patients with wound infections after posterior spinal surgery from 2014 to 2017 at a single tertiary center. All patients included in the study received modified VAC treatment (VAC combined with a closed suction irrigation system, CSIS) until the wound satisfied the secondary closure conditions. Detailed information was obtained from the medical records. RESULTS: Wound size decreased significantly after 1 week of the modified VAC treatment. Three patients were treated with VAC three times and one patient received the VAC treatment four times; the remaining patients received the VAC treatment twice. The patients had excellent wound beds after an average of 8 days. The wound healed completely after an average of 17 days, and the average hospital stay was 33 days. There was no recurrence of infection at the 1-year follow-up. CONCLUSIONS: This study demonstrates that VAC combined with a CSIS is a safe, reliable, and effective method to treat a wound infection after spinal surgery. This improved VAC procedure provides an excellent wound bed to facilitate wound healing and shorten the hospital stay.


Subject(s)
Bacterial Infections/therapy , Negative-Pressure Wound Therapy/methods , Spinal Fusion , Surgical Wound Infection/therapy , Adult , Aged , Aged, 80 and over , Bacterial Infections/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Suction/methods , Surgical Wound Infection/pathology , Therapeutic Irrigation/methods , Treatment Outcome
10.
Front Pharmacol ; 9: 1178, 2018.
Article in English | MEDLINE | ID: mdl-30405410

ABSTRACT

Random-pattern skin flap transplantation is frequently applied in plastic and reconstructive surgery. However, the distal part of the flap often suffers necrosis due to ischemia. In this study, the effects of salvianolic acid B (Sal B) on flap survival were evaluated, and the underlying mechanisms were investigated. Sal B improved the survival area, reduced tissue edema, and increased the number of microvessels in skin flaps after 7 days, whereas an autophagy inhibitor (3-methyladenine) reversed the Sal B-induced increase in flap viability. In addition, Sal B stimulated angiogenesis, inhibited apoptosis, reduced oxidative stress, and upregulated autophagy in areas of ischemia. Moreover, the effects of Sal B on angiogenesis, apoptosis, and oxidative stress were reversed by autophagy inhibition. Overall, our findings suggest that Sal B has pro-angiogenesis, anti-apoptosis, and anti-oxidative stress effects by stimulating autophagy, which enhances the survival of random-pattern skin flaps.

11.
Drug Des Devel Ther ; 12: 2267-2276, 2018.
Article in English | MEDLINE | ID: mdl-30087551

ABSTRACT

BACKGROUND: Random skin flaps are routinely placed during plastic and reconstructive surgery, but the distal areas often develop ischemia and necrosis. Baicalein, a major flavonoid extracted from the traditional Chinese herbal medicine huangqin, Scutellaria baicalensis Georgi, may improve flap viability. MATERIALS AND METHODS: Rats were randomly divided into baicalein and control groups and they underwent placement of modified McFarlane flaps after intraperitoneal administration of baicalein or vehicle. Flap survival and water content were measured 7 days later, as were angiogenesis, apoptosis, and oxidative stress in ischemic flaps. RESULTS: Baicalein promoted flap survival, reduced edema, increased mean vessel density, and enhanced vascular endothelial growth factor production at both the translational and transcriptional levels. Baicalein reduced caspase 3 cleavage, increased superoxidase dismutase and glutathione levels, and decreased the malondialdehyde level. CONCLUSION: Baicalein promoted flap viability by stimulating angiogenesis and inhibiting apoptosis and oxidation.


Subject(s)
Edema/drug therapy , Flavanones/pharmacology , Medicine, Chinese Traditional , Skin/drug effects , Surgical Flaps , Animals , Apoptosis/drug effects , Edema/metabolism , Edema/pathology , Male , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley
12.
Med Sci Monit ; 24: 4745-4752, 2018 Jul 09.
Article in English | MEDLINE | ID: mdl-29985910

ABSTRACT

BACKGROUND This study investigated the influence of surgical timing on the treatment of terrible triad of the elbow (TTE). MATERIAL AND METHODS After exclusion, 63 patients were enrolled in this study: 20 patients were classified into the emergency group (group A, within 24 h after injury), 26 into the early surgery group (group B, from 4 to 14 days after injury), and 17 into the delayed surgery group (group C, more than 14 days after injury). All patients underwent the same approach, and elbow motion and complication rates were recorded and compared. RESULTS Fifty-eight patients were followed up (mean 20.5±1.9 months), and 5 patients had lost partial final data. At 1 month after the operation, elbow motion in group A was higher than in group B and group C (P<0.01); however, 3 or more months later, there was no distinct difference between group A and group B (P>0.05), while both group A and group B showed better outcomes than group C at all time points (P<0.05). Moreover, group A and group B had better higher elbow motion, MEPS, excellent and good rate than group C at the final clinical visit (all P<0.05). No postoperative pain or complication rate differences were found among the 3 groups except for elbow stiffness (2 in group A, 3 in group B, and 7 in group C) (P<0.05) which required reoperation to enhance elbow function. CONCLUSIONS Emergency or early operation for TTE patients were more effective than delayed operation.


Subject(s)
Elbow Joint/surgery , Adult , Elbow Joint/diagnostic imaging , Elbow Joint/physiopathology , Female , Follow-Up Studies , Forearm/physiopathology , Humans , Joint Dislocations/physiopathology , Joint Dislocations/surgery , Male , Middle Aged , Postoperative Care , Postoperative Complications/etiology , Preoperative Care , Range of Motion, Articular , Rotation , Time Factors , Treatment Outcome
13.
Oncol Res ; 26(9): 1335-1343, 2018 Oct 17.
Article in English | MEDLINE | ID: mdl-29510778

ABSTRACT

Long noncoding RNA (lncRNA) FEZF1-AS1 was demonstrated to facilitate cell proliferation and migration in some cancers. However, the functions of FEZF1-AS1 and its molecular mechanism in osteosarcoma remain to be elucidated. In our study, we found that the expression of FEZF1-AS1 was upregulated in osteosarcoma samples and cell lines compared with normal tissues or cells. Besides, we showed that the expression levels of FEZF1-AS1 in osteosarcoma patients were positively correlated with tumor metastasis and TNM stage. Additionally, FEZF1-AS1 knockdown inhibited cell proliferation, migration, and invasion in U2OS and MG63 cells, while upregulation had the opposite effects in vitro. Moreover, FEZF1-AS1 depletion inhibited tumor growth and metastasis in vivo. We found that FEZF1-AS1 sponged miR-4443 to promote NUPR1 expression in U2OS and MG63 cells. Furthermore, knockdown of miR-4443 abrogated FEZF1-AS1 silencing-induced inhibition of cell proliferation, migration, and invasion in osteosarcoma. Finally, we found that restoration of NUPR1 rescued the proliferation, migration, and invasion abilities of FEZF1-AS1-depleted U2OS and MG63 cells. Our study indicated that FEZF1-AS1 could promote osteosarcoma progression by sponging miR-4443 to promote NUPR1 expression. The FEZF1-AS1/miR-4443/NUPR1 axis may act as a novel therapeutic strategy for osteosarcoma treatment.

14.
Int J Surg ; 51: 49-55, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29367033

ABSTRACT

INTRODUCTION: Dislocation of the elbow associated with radial head and coronoid fracture, the so-called "terrible triad" of the elbow, is challenging to treat and has a history of complicated outcomes. This study is to compare the clinical outcome of a single lateral approach-the extensile splitting extensor digitorum communis (EDC) approach and combined lateral and medial (CML) approaches for the treatment of terrible traid of the elbow (TTE). MATERIAL AND METHODS: After appropriate exclusion, 60 TTE patients (28 patients in the EDC group, 32 patients in the CML group) from 2009 January to 2015 August were reviewed in this study. All included patients underwent open reduction, lateral collateral ligament complex repair, and postoperative function exercise. Surgical time, intraoperative blood loss, postoperative pain, elbow motion, MEPS score and complication rate were recorded and compared. RESULT: There were significant differences in surgery time (P < 0.05) and ulnar nerve lesion symptom, no patient suffered ulnar nerve lesion symptom in EDC group, but 5 patients in CML group suffered it. No differences were found in intraoperative blood loss, postoperative pain and heterotopic ossification (P > 0.05). Mean follow-up was 26.1 months (from 24 to 30 months), at the final follow-up, 2 patients in EDC group and 4 patients in CML group required elbow release operation, mean flexion and extension (124.1 ±â€¯14.6°and 8.3 ±â€¯5.3°), pronation and supination (73.4 ±â€¯5.3° and 74.4 ±â€¯6.0°) in EDC group were higher than CML group (114.2 ±â€¯15.0° and 17.6 ±â€¯8.0°, 69.2 ±â€¯6.9° and 70.4 ±â€¯7.5°, P < 0.05). Besides, MEPS score in the former group was also higher than the latter group (91.8 ±â€¯4.5 to 84.4 ±â€¯5.2, P < 0.01). CONCLUSION: The single lateral approach achieved better function recovery than combined lateral and medial approach, decreasing the risk of ulnar nerve lesion and surgery time for the treatment of TTE.


Subject(s)
Elbow Injuries , Joint Dislocations/surgery , Open Fracture Reduction/methods , Radius Fractures/surgery , Ulna Fractures/surgery , Adult , Female , Humans , Male , Middle Aged , Operative Time , Postoperative Period , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Young Adult
15.
Am J Transl Res ; 9(9): 4161-4172, 2017.
Article in English | MEDLINE | ID: mdl-28979690

ABSTRACT

Random pattern skin flap transplantation is frequently applied in plastic and reconstructive surgery, but the distal part of skin flaps often suffers necrosis due to ischemia. Astragaloside IV (AS-IV), a natural saponin purified from Astragalus membranaceus, may have beneficial functions for flap survival. In this study, rats were divided into a control group and an AS-IV treatment group, and underwent surgery using a modified "McFarlane flap" model. After intragastric administration of vehicle control or AS-IV for their respective groups, flap survival area and water content were measured 7 days after surgery. Flap tissue was separated to test protein expressions related to angiogenesis, inflammation, oxidative stress and autophagy via western blot, immunohistochemistry, and immunofluorescence. Results showed that AS-IV improved flap survival area and reduced tissue edema. AS-IV also increased mean vessel densities and upregulated levels of VEGF protein, both of which indicate increased angiogenesis. Furthermore, AS-IV depressed leukocyte infiltration, decreased expressions of inflammatory proteins TNF-α, IL1ß and IL6, increased SOD activity, decreased MDA content, and stimulated autophagy. Overall, our results suggest that AS-IV promotes skin flap survival via inducing angiogenesis, depressing inflammation and dampening oxidative stress; it also activates autophagy, which may be an underlying mechanism for oxidative stress depression.

16.
Exp Biol Med (Maywood) ; 242(10): 1044-1050, 2017 05.
Article in English | MEDLINE | ID: mdl-28399646

ABSTRACT

BACKGROUND: Chondrosarcoma is one of the common malignant histologic tumors, very difficult to treat, but the concrete cause and mechanism have not yet been elucidated. The present study aimed to investigate the functional involvement of BCAR4 in chondrosarcoma and its potentially underlying mechanism. QRT-PCR and western blot were used to determine the expression of BCAR4 and mTOR signaling pathway proteins both in chondrosarcoma tissues and cells. Chondrosarcoma cell proliferation and migration were assessed by MTT assay and transwell migration assay, respectively. The expression vectors were constructed and used to modulate the expression of BCAR4 and mTOR. Chondrosarcoma xenograft mouse model was established by subcutaneous injection with chondrosarcoma cell lines. The tumor volume was monitored to evaluate the effect of BCAR4 on chondrosarcoma cell tumorigenicity. The expressions of BCAR4, p-mTOR and p-P70S6K were up-regulated in chondrosarcoma tissues and cell lines. Moreover, BCAR4 overexpression had significant promoting effect on cell proliferation and migration in chondrosarcoma cells. Furthermore, mTOR signaling pathway was epigenetically activated by BCAR4-induced hyperacetylation of histone H3. We also found that mTOR overexpression abolished the decrease of chondrosarcoma cell proliferation and migration induced by BCAR4 knockdown. In vivo experiments confirmed that BCAR4 overexpression significantly accelerated tumor growth, while the knockdown of BCAR4 significantly inhibited tumor growth. BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. Impact statement LncRNA BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression.


Subject(s)
Cell Movement , Cell Proliferation , Chondrosarcoma/pathology , RNA, Long Noncoding/analysis , Signal Transduction , TOR Serine-Threonine Kinases/analysis , Animals , Blotting, Western , Cell Line, Tumor , Disease Models, Animal , Gene Expression Profiling , Heterografts , Humans , Mice , Real-Time Polymerase Chain Reaction
17.
BMC Musculoskelet Disord ; 17: 288, 2016 07 15.
Article in English | MEDLINE | ID: mdl-27422705

ABSTRACT

BACKGROUND: The management of displaced intra-articular calcaneal fractures (DIACFs) remains challenging and controversial. A prospective randomized controlled trial was conducted to compare percutaneous reduction, cannulated screw fixation and calcium sulfate cement (PR+CSC) grafting with minimally invasive sinus tarsi approach and plate fixation (MISTA) for treatment of DIACFs. METHODS: Ultimately, 80 patients with a DIACFs were randomly allocated to receive either PR+CSC (N = 42) or MISTA (N = 38). Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores. Radiological results were assessed using plain radiographs and computed tomography (CT) scans, and postoperative wound-related complications were also recorded. RESULTS: The average time from initial injury to operation and the average operation time in the PR+CSC group were both significantly shorter than those in the MISTA group (p < 0.05). There were significantly fewer complications in the PR+CSC group than those in the MISTA group (7.1 % vs 28.9 %, p < 0.001). The calcaneal width immediate postoperatively and at the final follow-up in the MISTA group were obviously improved compared to those in the PR+CSC group (p < 0.001). The variables of sagittal motion and hindfoot motion of the AOFAS scoring system in the PR+CSC group were significantly higher than those in the MISTA group (p < 0.05). The good and excellent results in the two groups were comparable for Sanders Type-II calcaneal fractures, but the good to excellent rate in the MISTA group was significantly higher for Sanders Type-III fractures (p < 0.05). CONCLUSION: The clinical outcomes are comparable between the two minimally invasive techniques in the treatment of Sanders Type-II DIACFs. The PR+CSC grafting is superior to the MISTA in terms of the average time between initial injury and operation, operation time, wound-related complications and subtalar joint activity. However, the MISTA has its own advantages in improving the calcaneal width, providing a more clear visualization and accurate reduction of the articular surface, especially for Sanders Type-III DIACFs. TRIAL REGISTRATION: ChiCTRIOR16008512 . 21 May 2016.


Subject(s)
Bone Cements/therapeutic use , Calcaneus/injuries , Calcium Sulfate/therapeutic use , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Intra-Articular Fractures/surgery , Adult , Aged , Bone Plates , Bone Screws , Calcaneus/diagnostic imaging , Calcaneus/surgery , Female , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/instrumentation , Fractures, Bone/diagnostic imaging , Heel/diagnostic imaging , Heel/surgery , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Operative Time , Postoperative Complications/epidemiology , Prospective Studies , Radiography , Range of Motion, Articular , Subtalar Joint/physiology , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
18.
Orthopedics ; 38(11): e976-82, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26558677

ABSTRACT

Crescent fracture-dislocation of the sacroiliac joint (CFDSIJ) is a type of lateral compression pelvic injury associated with instability. Open reduction and internal fixation is a traditional treatment of CFDSIJ. However, a minimally invasive method has never been reported. The purpose of this study was to assess the outcome of closed reduction and percutaneous fixation for different types of CFDSIJ and present their clinical outcome. The authors reviewed 117 patients diagnosed with CFDSIJ between July 2003 and July 2013. Closed reduction and percutaneous fixation was performed in 73 patients. Treatment selection was based on Day's fracture classification. For type I fractures, fixation perpendicular to the fracture line were performed. For type II fractures, crossed fixation was performed. For type III fractures, fixation was performed with iliosacral screws. Forty-four patients were treated by open reduction and plate fixation. Demographics, fracture pattern distribution, blood loss, incision lengths, revision surgeries, radiological results, and functional scores were compared. All 117 patients were followed for more than 6 months (mean, 14 months [range, 6-24 months]). Blood loss, extensive exposure, duration of posterior ring surgery, duration of hospital stay, and infection rates were lower in the closed group (P<.01). Patients in the closed group achieved better functional performance (P<.01). There were no significant differences in reduction quality (P=.32), revision surgery rates (P=.27), and iatrogenic neurologic injuries (P=.2) between the 2 groups. The authors' results indicate that closed reduction and percutaneous fixation is a safe and effective surgical method for CFDSIJ.


Subject(s)
Bone Screws , Fracture Fixation, Internal , Fractures, Bone/therapy , Joint Dislocations/therapy , Manipulation, Orthopedic , Sacroiliac Joint/surgery , Adult , Blood Loss, Surgical , Female , Fractures, Bone/classification , Humans , Length of Stay , Male , Retrospective Studies , Sacroiliac Joint/injuries
19.
Arch Orthop Trauma Surg ; 135(8): 1093-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26130438

ABSTRACT

PURPOSES: Our objective was to measure the sagittal plane rotational (flexion and extension) displacement of hemipelvis radiologically and analyze the ratio of flexion and extension displacement of unstable pelvic fractures. METHODS: We used 8 cadaveric models to study the radiographic evidence of pelvic fractures in the sagittal plane. We performed pelvic osteotomy on 8 cadavers to simulate anterior and posterior pelvic ring injury. Radiological data were measured in the flexion and extension group under different angles (5°, 10°, 15°, 20°, and 25°). We retrospectively reviewed 164 patients who were diagnosed with a unilateral fracture of the pelvis. Pelvic ring displacement was identified and recorded radiographically in cadaveric models. RESULTS: The flexion and extension displacement of pelvic fractures was measured in terms of the vertical distance of fracture from the top of iliac crest to the pubic tubercle (CD) or from the top of iliac crest to the lowest point of ischial tuberosity (AB). Fifty-seven pelves showed flexion displacement and 15 showed extension displacement. Closed reduction including internal fixation and external fixation was successfully used in 141 cases (86.0 %). The success rates of closed reduction in flexion and extension displacement groups were 77 and 73 %, respectively, which were lower than in unstable pelvic ring fractures. CONCLUSIONS: The sagittal plane rotation (flexion and extension) displacement of pelvic fractures could be measured by special points and lines on the radiographs. Minimally invasive reduction should be based on clearly identified differences between the sagittal plane rotation and the vertical displacement of pelvic fractures.


Subject(s)
Fractures, Bone/diagnostic imaging , Pelvic Bones/diagnostic imaging , Adult , Cadaver , External Fixators , Female , Fracture Fixation, Internal , Fractures, Bone/surgery , Humans , Imaging, Three-Dimensional , Male , Pelvic Bones/injuries , Pelvic Bones/surgery , Radiography , Retrospective Studies , Rotation
20.
Zhongguo Gu Shang ; 28(10): 884-7, 2015 Oct.
Article in Chinese | MEDLINE | ID: mdl-26727777

ABSTRACT

OBJECTIVE: To study on the reliability of the Akagi line as a reference axis to guide for rotational alignment of the proximal tibial component in total knee arthroplasty (TKA) the rotational alignment reference bony landmarks of the proximal tibial component on magnetic resonance image (MRI) were measured. METHODS: From January 2010 to December 2013, 80 normal knees of Chinese volunteers including 35 males and 45 females with an average age of (35.4±6.1) years were reviewed. The images of the knees were obtained by MRI. The surgical epicondylar axis (STEA) was identified in the femoral transverse sections and then was projected to the side of tibia, forming the SETA'. A line connecting the medial border of the patellar tendon and the middle of the posterior cruciate ligament insertion (Akagi line) and its vertical line (AK), as well as a line connecting the medial 1/3 of the patellar tendon and the middle of the posterior cruciate ligament insertion and its vertical line (AP), were identified in the tibial transverse sections. The angles were measured between the AK, AP and STEA'. RESULTS: The angle between AK and STEA' was (0.59±2.07)°, and there was no significant difference between the two lines (t=-2.54, P=0.13). The mean angle between AP and STEA' was (3.21±2.04)°, and there was a significant difference between the two lines (t=14.05, P<0.05). There was a significant difference between the AK and AP (t=-11.68, P<0.05). CONCLUSION: The reliability of the Akagi line as a reference axis to guide for rotational alignment of the proximal tibial component in TKA is good.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Tibia/surgery , Adolescent , Adult , Female , Humans , Male , Middle Aged , Reproducibility of Results , Rotation
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