Publications by authors named "Honghui Sun"

24 Publications

  • Page 1 of 1

Pain location is associated with fracture type in acute osteoporotic thoracolumbar vertebral fracture: a prospective observation study.

Pain Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Spine Surgery, Honghui Hospital of Xi'an Jiaotong University Health Science Center.

Objective: This study investigated the relationship between pain location and fracture type in the patients with acute osteoporotic vertebral fracture (OVF).

Design: A prospective observation study.

Subject: A total of 306 patients with acute OVF were included.

Methods: The site of pain of each patient was recorded, and the patients were divided into pain at fracture site group (group 1) and pain at non-fracture site group (group 2). The fracture type was classified into four types: type I, upper endplate type; type II, central type; type III, lower endplate type; type IV, burst type.

Results: There were 146 patients in the group 1, of which 20.55% (30/146) were type I, 33.56% (49/146) were type II, 15.75% (23/146) were type III, and 30.14% (44/146) were type IV. There were 227 patients in the group 2, of which 57.27% (130/227) were type I, 5.29% (12/227) were type II, 35.24% (80/227) were type III, and 2.20% (5/227) were type IV. There was a statistical difference in the fracture type distribution between the two groups (P < 0.05). The VAS in the group 1 was higher than that in the group 2 at the initial diagnosis (P < 0.05).

Conclusions: For patients with acute OVF, the site of pain is related to the type of fracture. The pain at the fracture site is more often observed in the central type and burst type of fractures, while pain at the non-fracture site is more often observed in the upper and lower endplate type of fractures. Additionally, when OVF are suspected, radiological assessment of thoracic and lumbar spine is recommended to better detect fractures that could cause pain distal to the site of the fracture.
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http://dx.doi.org/10.1093/pm/pnab229DOI Listing
July 2021

Network meta-analysis on efficacy and safety of different anti-CGRP monoclonal antibody regimens for prophylaxis and treatment of episodic migraine.

Neurol Res 2021 Jul 19:1-18. Epub 2021 Jul 19.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, PR China.

Background: Currently, studies have shown that anti-CGRP monoclonal antibodies are effective drugs for the prophylaxis and treatment of episodic migraine. Therefore, for the first time, we classified and concluded 10 treatment regimens according to the different doses, drugs, routes of administration, and courses of treatment, so as to provide a reference for further clinical studies.

Methods: We studied relevant randomized controlled trials (RCTs) published before August 2020 on PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials.

Results: Eleven RCTs involving 6397 patients were included in our analysis. Network meta-analysis results suggested that in the comparison of the average migraine days per month, Erenumab  (140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) were superior to placebo, Erenumab(7 mg), and the difference was statistically significant; Fremanezumab (225 mg, 675 mg) was superior to Erenumab (21 mg, 70 mg), and the difference was statistically significant; in the comparison of average medication days of acute migraine-specific drug per month, Erenumab (70 mg, 140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) was superior to placebo, and Erenumab (140 mg) and Galcanezumab (120 mg, 240 mg) were superior to Erenumab (70 mg), and the difference was statistically significant; there was no statistically significant difference in the average migraine days in the last month or in the medication days of acute migraine-specific drug.

Conclusion: Fremanezumab (225 mg) and Galcanezumab (120 mg) may be the best clinical protocol after a comprehensive assessment.
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http://dx.doi.org/10.1080/01616412.2021.1940672DOI Listing
July 2021

One-stage posterior en-bloc spondylectomy following reconstruction with individualized 3D printed artificial vertebrae for multi-segment thoracolumbar metastases: case report and literature review.

Am J Transl Res 2021 15;13(1):115-123. Epub 2021 Jan 15.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University College of Medicine Xi'an 710054, Shaanxi, China.

In thoracolumbar vertebral tumors, reconstruction of complex multi-segment thoracolumbar vertebrae after total en-bloc spondylectomy (TES) is still challenging. In recent years, with the development of 3D printing technology, individualized 3D printed artificial vertebrae have been attempted to reconstruct complex multi-segment thoracolumbar spine. Compared with traditional titanium mesh or bone transplantation, it helps reduce long-term complications, bringing a new dawn for reconstructing multi-segment thoracolumbar spine. A 69-year-old female complained of low back pain with limited motion for 1 month. More than 2 months ago, she underwent radical mastectomy due to breast cancer (Luminal A subtype). Imageology examination revealed an osteolytic lesion involving the T11-L1 vertebra. She was performed one-stage 3-segment (T11-L1) en-bloc spondylectomy via posterior approach, and then an artificial vertebrae produced by a novel individualized 3D printing technology was used for reconstruction. The patient was follow-up for 2 years, and she recovered well, with no tumor recurrence, and no complications after spinal reconstruction. The application of individualized 3D printed artificial vertebrae in multi-segment thoracolumbar spine reconstruction can not only reconstruct the bone defect more accurately through the individualized design, but the porous design is able to achieve biomechanical performance comparable to that of cancellous bone, and it is conducive to inducing bone growth, all of which help reduce long-term mechanical complications. Furthermore, the application of artificial vertebrae in surgery can significantly shorten the operation time, reduce intraoperative blood loss and reduce the risk of perioperative complications. Therefore, individualized 3D printed artificial vertebrae is a good choice for complex multi-segment thoracolumbar spine reconstruction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847514PMC
January 2021

Kinematic MRI Analysis of Reducible Atlantoaxial Dislocation for Decompression.

Biomed Res Int 2020 15;2020:5395071. Epub 2020 Dec 15.

The Department of Spine Surgery, Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.

Background: Many doctors ignored the possibility that there is still a spinal cord compression (SCC) need for decompression after atlantoaxial reduction. Reduction can be achieved on kinematic magnetic resonance imaging (MRI); thus, we want to analyze the role of kinematic MRI in reducible atlantoaxial dislocation and make a preoperative decision whether to perform decompression.

Methods: 36 patients with atlantoaxial reduction on preoperative kinematic MRI in extension postures were enrolled retrospectively. Grouping was based on the condition of SCC after atlantoaxial reduction preoperatively. Group A: patients with SCC after atlantoaxial reduction on dynamic cervical MRI were treated with C1 laminectomy for decompression and atlantoaxial fixation. Group B: patients with no significant SCC, according to dynamic MRI, underwent only atlantoaxial fixation. Clinical outcomes were evaluated using JOA score for spinal cord function. Radiological outcomes were assessed by measuring spinal cord diameter on MRI.

Results: The mean follow-up time was 17.1 months. Postoperative JOA score and percentage of SCC in both groups were significantly better than its preoperative score. There were no significant statistical differences in the JOA score at 12 months after surgery and the JOA improvement rate between two groups. All patients in the two groups had a lower percentage of SCC on preoperative extension MRI, compared with neutral MRI. No significant statistical differences in the spinal decompression improvement rate were observed between the two groups.

Conclusions: Decompression should be performed in patients who still have significant SCC on preoperative kinematic MRI. Kinematic MRI could be used to assess SCC and decide whether to perform decompression preoperatively.
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http://dx.doi.org/10.1155/2020/5395071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755474PMC
June 2021

Novel Approach for Efficient Recovery for Spinal Cord Injury Repair via Biofabricated Nano-Cerium Oxide Loaded PCL With Resveratrol to Improve in Vitro Biocompatibility and Autorecovery Abilities.

Dose Response 2020 Jul-Sep;18(3):1559325820933518. Epub 2020 Sep 2.

Department of Orthopedic, Hong-Hui Hospital, Xi' an Jiaotong University College of Medicine, Xi'an, Shaanxi Province, People's Republic of China.

It is more difficult to develop the low-cost spinal cord injury repair materials with high stability and biocompatibility for the biomedical applications. Herein, for the first time, we demonstrated the functional restoration of an injured spinal cord by the nano CeO particles assembled onto poly (∊-caprolactone) (PCL)/resveratrol (RVL) were synthesized using the biocompatible ionic liquid. The as-prepared biocompatible nanomaterials were characterized and confirmed by using different instruments such as Fourier transform infra-red spectroscopy for functional groups identification, X-ray diffraction for crystalline nature, Scanning electron microscopy, transmission electron microscopy for morphological structure, Dynamic light scattering for size distribution of the nanoparticles and thermogravimetric analysis for thermal properties. The synergetic effect between the uniform distributions of nano-sized CeO particles onto the PCL polymer with RVL can remarkably enhance the catalytic performance. Biofabricated nano-cerium oxide loaded PCL with RVL revealed that treatment significantly preserved hydrogen peroxide and also good catalytic performance. This study presents a nano-sized cerium oxide particles loaded PCL with RVL biocompatible materials have been providing highly efficient regenerative activity and biocompatibility in spinal card regeneration.
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http://dx.doi.org/10.1177/1559325820933518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476352PMC
September 2020

Effect of Vicenin-2 on ovariectomy-induced osteoporosis in rats.

Biomed Pharmacother 2020 Sep 10;129:110474. Epub 2020 Jul 10.

Department of Spinal Surgery, Honghui Hospital, Xi'an Jiaotong University College of Medicine, No.555 Youyi East Road, Beilin District, Xi'an, Shaanxi, 710054, China. Electronic address:

In worldwide, osteoporosis has become one of the severe public health distress and over 200 million people get affected by tenderness and fissure during their life period. Vicenin-2 is a naturally occurring flavonoid glycoside present in Moringa oleifera, Peperomia blanda and Ocimum sanctum Linn with numerous biological activities. The present study aims to assess the effect of Vicenin-2 on ovariectomy-induced postmenopausal osteoporosis in female rats. Surgical removal of ovaries was achieved to institute the ovariectomy animal model. The ovariectomized (OVX) animals were alienated into four groups: Control, OVX alone (model), OVX with Vicenin-2 (5 mg/kg b.w), and OVX with Vicenin-2 (10 mg/kg b.w). Also, their consistent conduct remained managed intragastrically for about 12 weeks. OVX rats treated with Vicenin-2 effectually improved body mass, uterus index, lipid profiles, inflammatory markers, bone turnover markers and amplified the presence of calcium in the OVX rat serum. Vicenin-2 was found to suppress the actions of ACP, E2, and BGP in OVX rats. Besides, Vicenin-2 showed some adverse effects over histomorphometric percentage and histological studies, in which tabular thickness and area were restored in the control and Vicenin-2 managed OVX rats. PCR results of Alp, Runx 2, Osx showed diminished expressions in OVX rats whereas treatment with Vicenin-2 displays up-regulated expression of these genes. Through our study, we established that Vicenin-2 did not wield a detrimental upshot on the skeletal organization of OVX rats. Besides, we put forward that Vicenin-2 could be an excellent candidate to treat and manage bone related disease or disorders.
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http://dx.doi.org/10.1016/j.biopha.2020.110474DOI Listing
September 2020

Effect of Huatan Jieyu granules in treatment of Parkinson's disease patients with sleep disorder identified as symptom pattern of phlegma-heat-stirring wind.

J Tradit Chin Med 2020 06;40(3):461-466

Medical Department of Neurology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.

Objective: To investigate the safety and efficacy of Huatan Jieyu granules in treatment of Parkinson's disease (PD) patients with sleep disorder identified as symptom pattern of phlegma-heat-stirring wind in terms of the theory of Traditional Chinese Medicine.

Methods: In total, 107 Parkinson's disease patients with sleep disorders identified as symptom pattern of phlegma-heat-stirring wind were selected and randomly divided into the experimental group (55 cases) and the control group (52 cases). Both groups were given basic treatment with prednisone. The experimental group of patients was treated with Huatan Jieyu granules and the control group of patents was treated with only the basic treatment. Treatment lasted for 4 weeks. Sleep polygraph were recorded before the study as well as 3 months and 6 months after treatment.

Results: After treated with Huatan Jieyu granules, the total sleep time, and the percentage of non rapid eye movement 2 (NREM 2), non rapid eye movement 3 (NREM 3) and rapid eye movement (REM) sleep period increased significantly, while the percentage of NREM1 sleep period decreased significantly compared with before treatment (P < 0.05).

Conclusion: The treatment of PD patients with sleep disorder by Huatan Jieyu granules can improve their sleep structure and their sleep quality.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.03.015DOI Listing
June 2020

Biomechanical effects of direction-changeable cage positions on lumbar spine: a finite element study.

Am J Transl Res 2020 15;12(2):389-396. Epub 2020 Feb 15.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University Health Science Center Xi'an, Shaanxi, China.

This finite element (FE) study of lumbar biomechanics aims to predict how the parameters like range of motion (ROM), intervertebral disc pressure (IDP), cage stress and screw stress are affected by different direction-changeable cage positions. Firstly, the three-dimensional FE model of L3-L5 segment was developed, and the model was adjusted to adapt different direction-changeable cage positions at the L4-L5 level though transforaminal lumbar interbody fusion (TLIF) with pedicle screws. The effects of Type A (the lateral region), Type B (the lateralcentral region) and Type C (the anteriocentral region) on ROM, IDP, cage stress and screw stress were examined. The results showed that after implantation of interbody cages at different positions, the ROM at surgical level L4-L5 decreased substantially in all motion modes. The maximal stress in cage decreased with Type A, B and C in all motion modes except flexion and extension. The maximal cage stress was observed in Type A with 720.5 MPa in left rotation, in Type B with 707 MPa in flexion, in Type C with 397.3 MPa in left rotation, respectively. The maximal IDP was similar in three types, with 1.6 MPa in left lateral bending in Type A, 1.5 MPa in flexion in Type B, and 1.4 MPa in flexion in Type C. The range of screw peak stress was 16.4 to 61.1 MPa in Type A, 15.9 to 50.9 MPa in Type B, and 14.6 to 46.1 MPa Type C. In conclusion, comparing the cages with different positions, anteriocentral position cage has more advantages like lower cage stress, ODL and screw stress.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061850PMC
February 2020

Different Effects of Intravenous, Topical, and Combined Application of Tranexamic Acid on Patients with Thoracolumbar Fracture.

World Neurosurg 2019 Jul 17;127:e1185-e1189. Epub 2019 Apr 17.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

Objective: To observe the efficacy of intravenous, topical, and combined application of tranexamic acid (TXA) in patients with thoracolumbar fracture fixed with percutaneous pedicle screw, and to identify the optimal application method of TXA.

Methods: A total of 181 patients with thoracolumbar fracture treated with percutaneous pedicle screw fixation were enrolled in this randomized controlled trial and were randomly classified into 3 groups, including group A (intravenous group), group B (topical group), and group C (combined group). The total blood loss (TBL), hidden blood loss (HBL), intraoperative blood loss (IBL), preoperative D-dimer, postoperative D-dimer, incidence of deep vein thrombosis (DVT), and incidence of other complications were compared and analyzed among the 3 groups.

Results: TBL, HBL, and IBL in the topical group 24 hours after operation were higher (P < 0.05) than those in the intravenous group and combined group, whereas the difference between the intravenous group and combined group was not statistically significant. Meanwhile, there was no statistically significant difference in operation time, preoperative D-dimer, and postoperative D-dimer among the 3 groups (P > 0.05), but D-dimer in all groups at 72 hours after surgery was higher than that before surgery. No DVT or other complication was observed in the patients.

Conclusions: Preoperative intravenous drip of TXA can remarkably reduce intraoperative HBL and IBL in patients with thoracolumbar fracture fixed with percutaneous pedicle screw. Nonetheless, intraoperative topical application of TXA before wound closure is not recommended.
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http://dx.doi.org/10.1016/j.wneu.2019.04.095DOI Listing
July 2019

Pattern Formation in Drying Sessile and Pendant Droplet: Interactions of Gravity Settling, Interface Shrinkage, and Capillary Flow.

Langmuir 2019 01 20;35(1):113-119. Epub 2018 Dec 20.

National Microgravity Laboratory, Institute of Mechanics , Chinese Academy of Sciences , 100190 Beijing , China.

We reported the interactions of the gravitational sedimentation, interface shrinkage, and outward capillary flow in drying droplets. This coupling effect is the inference we draw from deposition patterns of both sessile and pendant droplets, which contain particles of different sizes, evaporating on a patterned substrate. The deposition difference between sessile and pendant droplets containing microparticles indicated that gravitational sedimentation has a significant influence on the deposition morphology. The phase diagram shows that the particle deposition process can be divided into two stages: in the first stage, the competition between the interface shrinkage and the gravitational sedimentation determines whether the particles can be captured by the liquid-air interface; in the second stage, the capillary flow takes the particles inside the droplet toward the edge. The deposition morphology is the result of competition and cooperation interactions of the free setting, interface shrinkage, and outward capillary flow.
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http://dx.doi.org/10.1021/acs.langmuir.8b02659DOI Listing
January 2019

Drop Capturing Based on Patterned Substrate in Space.

Langmuir 2018 04 13;34(16):4715-4721. Epub 2018 Apr 13.

National Microgravity Laboratory, Institute of Mechanics , Chinese Academy of Sciences , 100190 Beijing , China.

In this work, we introduced a method for capturing aqueous drop based on a patterned substrate in space. Through the manipulation test of a colloidal drop, it could be verified that this patterned substrate had excellent control ability for aqueous drop in microgravity condition. The confinement mechanism of this substrate was clarified, which showed that drops with different volume could be pinned and attracted at a given area on the substrate. The confinement capability was related to the gravity effect, and the patterned substrate could confine aqueous drops with larger volume under microgravity than in normal gravity. With advantages of simple operation and strong capability to control large drops, this technique exhibited the wide application prospect in the fields of fluid management, biosensing, and pharmacy in microgravity condition in the future.
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http://dx.doi.org/10.1021/acs.langmuir.8b00219DOI Listing
April 2018

Pretreatment with AQP4 and NKCC1 Inhibitors Concurrently Attenuated Spinal Cord Edema and Tissue Damage after Spinal Cord Injury in Rats.

Front Physiol 2018 19;9. Epub 2018 Jan 19.

Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na-K-Cl cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.
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http://dx.doi.org/10.3389/fphys.2018.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780344PMC
January 2018

Correction: Broadband ultrafast photovoltaic detectors based on large-scale topological insulator SbTe/STO heterostructures.

Nanoscale 2017 08;9(33):12196

State Key Laboratory of High Performance Computing, College of Computer, National University of Defense Technology, Changsha 410073, China.

Correction for 'Broadband ultrafast photovoltaic detectors based on large-scale topological insulator SbTe/STO heterostructures' by Honghui Sun, et al., Nanoscale, 2017, 9, 9325-9332.
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http://dx.doi.org/10.1039/c7nr90164jDOI Listing
August 2017

Broadband ultrafast photovoltaic detectors based on large-scale topological insulator SbTe/STO heterostructures.

Nanoscale 2017 Jul;9(27):9325-9332

State Key Laboratory of High Performance Computing, College of Computer, National University of Defense Technology, Changsha 410073, China.

Topological insulators (TIs) are new states of quantum matter in which the spin-momentum-locked surface states reside in the bulk insulating gap and have triggered extensive investigations on fundamental properties and potential applications. Herein, we report scalable, broadband photovoltaic detectors based on the topological insulator SbTe/strontium titanate (STO) heterostructure. Large-scale (2 mm × 5 mm), high crystalline quality p-type SbTe films were fabricated on an n-type STO substrate by the molecular beam epitaxy (MBE) method. The SbTe/STO heterostructures exhibited pronounced photovoltaic behavior in a wide range of temperatures as a result of a strong built-in field at the hetero-interface. Superior performances of broadband (from visible to infrared, 405 nm-1550 nm) and ultrafast (rise time ∼30 μs, fall time ∼95 μs) photoresponses were achieved under ambient conditions. The prominent repeatability and stability indicated that our photodetectors can operate effectively in harsh circumstances. These results show that stacking the topological insulator thin films on a strongly correlated oxide substrate using the MBE approach holds great promise for high performance optoelectronic applications.
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http://dx.doi.org/10.1039/c7nr01715dDOI Listing
July 2017

Sirtuin 3 is required for osteogenic differentiation through maintenance of PGC-1ɑ-SOD2-mediated regulation of mitochondrial function.

Int J Biol Sci 2017 12;13(2):254-264. Epub 2017 Feb 12.

Department of Orthopedic, Tangdu Hospital, Fourth Military Medical University, #569 Xinsi Road, Xi'an 710038, China.

Osteogenic differentiation is crucial for the maintenance of bone homeostasis. Sirtuin 3 (SIRT3), a member of sirtuins family, functions as a critical deacetylase that regulates many key proteins. In the current study, we aimed to clarify the role of SIRT3 in osteogenic differentiation and the possible mechanisms, using mouse pre-osteoblastic MC3T3-E1 cells. Expression of SIRT3 was substantially increased in differentiated MC3T3-E1 cells. Knock down of SIRT3 significantly decreased alkaline phosphatase (ALP) staining, and mRNA expression of runt-related transcription factor 2 (Runx2) and collagen type I ɑ 1 (Col1ɑ1), and osteocalcin in differentiated MC3T3-E1 cells. Overexpression of wild type but not mutant SIRT3 could reverse SIRT3 knockdown-resulted decrease of ALP staining. Complex I, II, III, IV, and V activities, oxygen consumption and mitochondrial membrane potential were significantly decreased by SIRT3 knockdown. Moreover, SIRT3 knockdown reduced mitochondrial density, increased mitochondrial size and decreased the expression of NRF1 and TFAM. Knock down of SIRT3 decreased mRNA and protein expression of SOD2 and increased ROS level. Overexpression of SOD2 significantly suppressed SIRT3 knockdown-induced decrease of mitochondrial function and osteogenic differentiation. SIRT3 knockdown resulted in a significant decrease of PGC-1ɑ protein expression but not mRNA expression. Overexpression of wild type but not mutant SIRT3 could reverse SIRT3 knockdown-resulted decrease of PGC-1ɑ protein expression. Moreover, we detected a direct interaction between SIRT3 and PGC-1ɑ and SIRT3 knockdown reduced SIRT3 and PGC-1ɑ interaction, resulting in a reduction of PGC-1ɑ protein stability and PGC-1ɑ-binding in the promoters of SOD2. Overexpression of PGC-1ɑ blocked SIRT3 knockdown-induced decrease of SOD2 expression, increase of ROS level, and decrease of mitochondrial function and biogenesis, leading to improvement of osteogenesis. Overall, the data provide a better understanding of the role of SIRT3 in osteogenic differentiation.
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http://dx.doi.org/10.7150/ijbs.17053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332879PMC
November 2017

Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA transcription through calcium-dependent activation of the ERK/CREB pathway.

Lasers Med Sci 2017 Jan 19;32(1):169-180. Epub 2016 Nov 19.

Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, China.

Low-level laser (LLL) irradiation has been reported to promote neuronal differentiation, but the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) has been confirmed to be one of the most important neurotrophic factors because it is critical for the differentiation and survival of neurons during development. Thus, this study aimed to investigate the effects of LLL irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion neurons (DRGNs) using Ca imaging, pharmacological detections, RNA interference, immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL induced increases in the [Ca] level, Bdnf mRNA transcription, cAMP-response element-binding protein (CREB) phosphorylation, and extracellular signal-regulated kinase (ERK) phosphorylation, mediated by Ca release via inositol triphosphate receptor (IP3R)-sensitive calcium (Ca) stores. Blockade of Ca increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA transcription triggered by LLL. Furthermore, blockade of ERK using PD98059 inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken together, these findings establish the Ca-ERK-CREB cascade as a potential signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our knowledge, this is the first report of the mechanisms of Ca-dependent Bdnf mRNA transcription triggered by LLL. These findings may help further explore the complex molecular signaling networks in LLL-triggered nerve regeneration in vivo and may also provide experimental evidence for the development of LLL for clinical applications.
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http://dx.doi.org/10.1007/s10103-016-2099-0DOI Listing
January 2017

Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress.

Cell Physiol Biochem 2016 11;38(3):1129-37. Epub 2016 Mar 11.

Background/aims: Spinal cord injury (SCI) is a severe health problem worldwide. Ryanodine receptors (RyRs) are a class of intracellular calcium channels in various excitable tissues such as muscles and nervous tissues. The current study was designed to investigate the possible role of RyR2 upregulation in SCI and to elucidate the possible molecular mechanisms.

Methods: Rats were injected with LVshRNAi- RyR2 and then exposed to spinal cord contusion injury.

Results: The results showed that knockdown of RyR2 significantly promoted the recovery of structural and functional injury in spinal cord, as evidenced by reduction of lesion volume and increase of Basso, Beattie and Bresnahan (BBB) and combined behavioral score (CBS) scores. Knockdown of RyR2 inhibited the increase of proinflammatory cytokines, including IL-1β and TNFα. Moreover, downregulation of RyR2 increased oxygen consumption rate and decreased the expression of glucose-regulated protein 78 (GRP78), activating transcription factor 3 (ATF3) and ATF6, indicating the improvement of mitochondrial dysfunction and endoplasmic reticulum stress after SCI. Furthermore, silence of RyR2 reduced oxidative stress, as reflected by decrease of TBARS and GSSG content and increase of GSH level. The expression of NADPH oxidase 2 (NOX2), NOX4 and p66(shc) were increased in SCI rats. Knockdown of RyR2 significantly decreased NOX2 expression, but had no evident effect on NOX4 and p66shc expression. These results indicated NOX2 may be involved in RyR2-induced ROS generation which mediated contusion-induced spinal cord injury.

Conclusion: The data provide novel insights into the mechanism of RyR2-mediated injury and the potential therapeutic targets for injury in spinal cord.
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http://dx.doi.org/10.1159/000443063DOI Listing
December 2016

MEF2D overexpression contributes to the progression of osteosarcoma.

Gene 2015 Jun 23;563(2):130-5. Epub 2015 Mar 23.

The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address:

The underlying molecular pathogenesis of osteosarcoma remains poorly understood. The transcription factor MEF2D promotes the survival of various types of cells and functions as an oncogene in liver cancer. However, its potential contribution to osteosarcoma has not been explored. In this study, we investigated MEF2D expression and function in osteosarcoma, finding that MEF2D elevation in osteosarcoma clinical specimens was associated with patients' poor prognosis. MEF2D suppression was shown to decrease the proliferation of osteosarcoma cells, while forced expression of MEF2D was able to promote the proliferation of normal bone fibroblast. Notably, MEF2D silencing abolished osteosarcoma tumorigenicity in an animal model. Mechanistic investigations revealed that MEF2D silencing triggered G2-M arrest in osteosarcoma cells by suppressing RPRM and CDKN1A. miR-144 was found to suppress the expression of MEF2D in osteosarcoma cells. Collectively, our results demonstrated that MEF2D is a candidate oncogene for osteosarcoma and a potential molecular target for cancer therapy.
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http://dx.doi.org/10.1016/j.gene.2015.03.046DOI Listing
June 2015

A polysaccharide from Sanguisorbae radix induces caspase-dependent apoptosis in human leukemia HL-60 cells.

Int J Biol Macromol 2014 Sep 15;70:615-20. Epub 2014 Jul 15.

Department of Haematology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China. Electronic address:

One polysaccharide (SRP) was purified from Sanguisorbae radix by DEAE-cellulose-52 anion-exchange and Sephacryl S-400 gel filtration chromatography. The aim of this study was to evaluate the anticancer efficacy of SRP on human leukemia HL-60 cells in vitro and unveil the underlying mechanisms. Our results showed that SRP was able to suppress the proliferation of HL-60 cells in a dose-dependent manner by the mechanism involved in the induction of apoptosis. The increase in SRP-induced apoptosis was correlated with a rapid and sustained loss of mitochondrial transmembrane potential (ΔΨm) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, Western blot and RT-PCR analysis revealed that the protein and mRNA levels of antiapoptotic Bcl-2 were downregulated, whereas those of pro-apoptotic Bax were upregulated. Besides, caspase-9 and caspase-3 were activated, while caspase-8 was intact. Additionally, the apoptotic cells by SRP were significantly inhibited by a caspase-3 inhibitor (z-DEVD-fmk) or a caspase-9 inhibitor (Z-LETD-FMK), demonstrating the important role of caspase-9 and -3 in the process. Taken together, these findings provided evidence that SRP induced the apoptosis of HL-60 cells through an intrinsic mitochondria-mediated signaling pathway and SRP may be a promising chemotherapeutic agent for treatment of leukemia.
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http://dx.doi.org/10.1016/j.ijbiomac.2014.06.062DOI Listing
September 2014

Pulsed electromagnetic field enhances brain-derived neurotrophic factor expression through L-type voltage-gated calcium channel- and Erk-dependent signaling pathways in neonatal rat dorsal root ganglion neurons.

Neurochem Int 2014 Sep 14;75:96-104. Epub 2014 Jun 14.

Second Clinical Medical College, Southern Medical University, Guangzhou 510280, PR China. Electronic address:

Although pulsed electromagnetic field (PEMF) exposure has been reported to promote neuronal differentiation, the mechanism is still unclear. Here, we aimed to examine the effects of PEMF exposure on brain-derived neurotrophic factor (Bdnf) mRNA expression and the correlation between the intracellular free calcium concentration ([Ca(2+)]i) and Bdnf mRNA expression in cultured dorsal root ganglion neurons (DRGNs). Exposure to 50Hz and 1mT PEMF for 2h increased the level of [Ca(2+)]i and Bdnf mRNA expression, which was found to be mediated by increased [Ca(2+)]i from Ca(2+) influx through L-type voltage-gated calcium channels (VGCCs). However, calcium mobilization was not involved in the increased [Ca(2+)]i and BDNF expression, indicating that calcium influx was one of the key factors responding to PEMF exposure. Moreover, PD098059, an extracellular signal-regulated kinase (Erk) inhibitor, strongly inhibited PEMF-dependant Erk1/2 activation and BDNF expression, indicating that Erk activation is required for PEMF-induced upregulation of BDNF expression. These findings indicated that PEMF exposure increased BDNF expression in DRGNs by activating Ca(2+)- and Erk-dependent signaling pathways.
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http://dx.doi.org/10.1016/j.neuint.2014.06.004DOI Listing
September 2014

Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway.

Tumour Biol 2014 Feb;35(2):1619-25

The cytostatic drug from traditional Chinese medicinal herb has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Oxymatrine, classified as a quinolizidine alkaloid, is a phytochemical product derived from Sophora flavescens, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma MNNG/HOS cell have not been well studied. In the present study, the cytotoxic effects of oxymatrine on MNNG/HOS cells were examined by MTT and bromodeoxyuridine (BrdU) incorporation assays. The percentage of apoptotic cells and the level of mitochondrial membrane potential (Δψ m) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by Western blot analysis or enzyme assay Kit. Our results showed that treatment with oxymatrine resulted in a significant inhibition of cell proliferation and DNA synthesis in a dose-dependent manner, which has been attributed to apoptosis. Furthermore, we found that oxymatrine considerably inhibited the expression of Bcl-2 whilst increasing that of Bax. This promoted mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the activation of caspase-9 and -3. Moreover, addition of oxymatrine to MNNG/HOS cells also attenuated phosphatidylinositol 3-kinase (PI3K) ⁄Akt signaling pathway cascade, evidenced by the dephosphorylation of P13K and Akt. Likewise, oxymatrine significantly suppressed tumor growth in female BALB/C nude mice bearing MNNG/HOS xenograft tumors. In addition, no evidence of drug-related toxicity was identified in the treated animals by comparing the body weight increase and mortality. Therefore, these findings should be useful for understanding the apoptotic cellular mechanism mediated by oxymatrine and might offer a therapeutic potential advantage for human osteosarcoma chemoprevention or chemotherapy.
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http://dx.doi.org/10.1007/s13277-013-1223-zDOI Listing
February 2014

Could local deliver of bisphosphonates be a new therapeutic choice for Gorham-Stout syndrome?

Med Hypotheses 2011 Feb 1;76(2):237-8. Epub 2010 Nov 1.

Department of Orthopaedic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shhanxi Province, 710038, China.

The Gorham-Stout Syndrome is a rare condition in which spontaneous, progressive resorption of bone occurs. Even though the prognosis of the condition is generally considered to be good, Gorham-Stout syndrome can cause severe debilitation. In approximately 13% of recorded cases, death ensues. The treatment modalities for Gorham-Stout Syndrome include surgery, radiation therapy, anti-osteoclastic medications, however there is no known successful treatment. To date, the etiology of Gorham-Stout Syndrome is still controversial. However, general consensus on the importance of the derangement of osteoclastic activity and angiomatosis of blood vessels. Thus, local deliver of anti-osteoclastic and anti-angiogenic agents may be of great interest for the treatment of Gorham-Stout Syndrome. Bisphosphonates are potent in inhibiting osteoclast activity and promoting apoptosis, which has been widely used for the treatment of osteoporosis and osteolysis diseases and proved to be able to decrease the speed of bone destruction in Gorham-Stout Syndrome through systemic administration. In addition to its anti-osteolytic effect, bisphosphonates are currently shown to be capable of anti-angiogenesis and induction of apoptosis in tumor cells. Furthermore biocompatible calcium phosphate which is widely used for bone reconstruction in clinical has also been reported to be a suitable carrier for loading and releasing of bioactive bisphosphonates. Therefore, we hypothesis that local deliver of bisphosphonates by calcium phosphate may be a potential treatment of Gorham-Stout Syndrome.
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http://dx.doi.org/10.1016/j.mehy.2010.10.006DOI Listing
February 2011

Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique.

Oncol Rep 2009 May;21(5):1175-80

Center of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Shaanxi 710038, PR China.

In experimental musculoskeletal oncology, there remains a need for animal models that can be used to assess the efficacy of new and innovative treatment methodologies for bone tumors. Rat plays a very important role in the bone field especially in the evaluation of metabolic bone diseases. The objective of this study was to develop a rat osteosarcoma model for evaluation of new surgical and molecular methods of treatment for extremity sarcoma. One hundred male SD rats weighing 125.45+/-8.19 g were divided into 5 groups and anesthetized intraperitoneally with 10% chloral hydrate. Orthotopic implantation models of rat osteosarcoma were performed by injecting directly into the SD rat femur with a needle for inoculation with SD tumor cells. In the first step of the experiment, 2x10(5) to 1x10(6) UMR106 cells in 50 microl were injected intraosseously into median or distal part of the femoral shaft and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from ultrasound with findings from necropsia and determining time of survival. In the third stage, the orthotopically implanted tumors and lung nodules were resected entirely, sectioned, and then counter stained with hematoxylin and eosin for histopathologic evaluation. The tumor take rate was 100% for implants with 8x10(5) tumor cells or more, which was much less than the amount required for subcutaneous implantation, with a high lung metastasis rate of 93.0%. Ultrasound and necropsia findings matched closely (r=0.942; p<0.01), which demonstrated that Doppler ultrasonography is a convenient and reliable technique for measuring cancer at any stage. Tumor growth curve showed that orthotopically implanted tumors expanded vigorously with time-lapse, especially in the first 3 weeks. The median time of survival was 38 days and surgical mortality was 0%. The UMR106 cell line has strong carcinogenic capability and high lung metastasis frequency. The present rat osteosarcoma model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. It may be a useful tool in the investigation of antiangiogenic and anticancer therapeutics. Ultrasound was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.
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http://dx.doi.org/10.3892/or_00000338DOI Listing
May 2009

Specific antitumor effects of tumor vaccine produced by autologous dendritic cells transfected with allogeneic osteosarcoma total RNA through electroporation in rats.

Cancer Biol Ther 2009 May 24;8(10):973-80. Epub 2009 May 24.

Center of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi China.

Objective: Transfection of dendritic cells with tumor-derived RNA has recently been shown to elicit tumor-specific CTL capable of recognizing and lysing a variety of tumor cells. However, the integration of allogeneic osteosarcoma mRNA and autologous DCs has not been fully examined. This study was designed to investigate the antitumor effects of tumor vaccine produced by autologous dendritic cells transfected with allogeneic osteosarcoma total RNA through electroporation in tumor-bearing rats model.

Results: The immunization using autologous DCs electrotransfected with allogeneic osteosarcoma total RNA induced UMR106-specific CTL responses which were statistically significant and the cytotoxic activity was inhibited by the treatment with anti-CD8 and anti-MHC-class I monoclonal antibodies. In in vivo experiments, 80% of the rats immunized with allogeneic osteosarcoma RNA transfected to DCs were typically able to reject tumor challenge and remained tumor-free. Vaccinated survivors developed long immunological memory and were able to reject a subsequent rechallenge with the same tumor cells but not a syngeneic unrelated tumor line.

Methods: In the present study, we transfected Wistar rat osteosarcoma cells derived total RNA to SD rat bone marrow-derived DCs through electroporation. The tumor vaccine was applied to in tumor-bearing rats model and the specific antitumor effects of the tumor vaccine were observed. Then CTL activity was evaluated one week after the first immunization of SD rats with electroporated DCs and the specificity of the cytotoxic activity was confirmed in cold target inhibition assays and using mAbs blocking MHC class I or CD8 molecules.

Conclusion: The present study provided valid evidence of integration of rat allogeneic tumor-derived mRNA and autologous DCs through electroporation and confirmed this novel tumor vaccine have the potential to induced osteosarcoma-specific CTL response and reject osteosarcoma challege. This technique and its products may thus represent a promising strategy for DC-based immunotherapy of patients with osteosarcoma.
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http://dx.doi.org/10.4161/cbt.8.10.8281DOI Listing
May 2009
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