Publications by authors named "Yingchao Han"

42 Publications

Inclination of the small laminar slope angle leads to lumbar spinal stenosis due to hypertrophy of the ligamentum flavum.

J Orthop Surg (Hong Kong) 2021 May-Aug;29(2):23094990211012846

Department of Orthopaedic Surgery, Renji Hospital, 56694Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: This study was designed to investigate the relationship between the laminar slope angle (LSA) and the lumbar disc degenerative grade, the cross-section area (CSA) of multifidus muscle, the muscle-fat index, and the thickness of the ligamentum flavum.

Methods: Retrospective analysis of 122 patients who were scheduled to undergo a lumbar operation for diagnoses associated with degenerative lumbar disease between January and December 2017. The L4-L5 disc grade was evaluated from preoperative sagittal T2-weighed magnetic resonance imaging of the lumber region; the CSA of the multifidus and muscle-fat index were measured at the L4 level, while the thickness of the ligamentum flavum was measured at the L4-L5 facet level from axis T2-weighed magnetic resonance imaging. The slope of the laminar was evaluated from preoperative three-dimensional computer tomography at the tip level of the facet joints and selected by the axis plane. Independent-sample T-tests were used to assess the association between age and measurement indices.

Results: Our results showed that age was positively connected with the LSA of L4 and L5 in different patients, although there was no significant difference between age and the difference of the two segment LSA. Partial correlation analysis, excluding the interference of age, revealed a strong negative relationship between the LSA of L4 and the thickness of the ligamentum flavum, irrespective of whether we considered the left or right. However, there was no correlation with lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index.

Conclusion: The thickness of the ligamentum flavum showed changes with anatomical differences in the LSA, but not the lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. A small change in LSA may cause large mechanical stress; this may be one of the causative factors responsible for lumbar spinal stenosis.
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http://dx.doi.org/10.1177/23094990211012846DOI Listing
April 2021

Robot-assisted minimally invasive transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion: a retrospective matched-control analysis for clinical and quality-of-life outcomes.

J Comp Eff Res 2021 Apr 28. Epub 2021 Apr 28.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

To compare the screw accuracy and clinical outcomes between robot-assisted minimally invasive transforaminal lumbar interbody fusion (RA MIS-TLIF) and open TLIF in the treatment of one-level lumbar degenerative disease. From May 2018 to December 2019, a consecutive series of patients undergoing robot-assisted minimally invasive one-level lumbar fusion procedures were retrospectively compared with matched controls who underwent one-level open TLIF procedures for clinical and quality-of-life outcomes. A total of 52 patients underwent RA MIS-TLIF procedures (robot-assisted [RA] group) and 52 matched controls received freehand open TLIF procedures (open [OP] group). The RA group had more grade A screws with 96.2% one-time success rate of screw placement (p < 0.05). Besides, the RA group experienced less intraoperative blood loss and shorter length of hospital stay, while the OP group had shorter operative duration and cumulative radiation time (p < 0.001). What is more, the average VAS score for low back pain and ODI score in the RA group were lower than that in the OP group 1 month after operation (p < 0.05). The use of real-time, image-guided robot system may further expand the advantages of MIS-TLIF technique in terms of accuracy and safety.
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http://dx.doi.org/10.2217/cer-2021-0078DOI Listing
April 2021

Relationship between the expression of TNFR1-RIP1/RIP3 in peripheral blood and cognitive function in occupational Al-exposed workers: A mediation effect study.

Chemosphere 2021 Apr 3;278:130484. Epub 2021 Apr 3.

Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, China. Electronic address:

Aluminium (Al), not essential for biological activities, accumulates in the tissues. It exerts toxic effects on the nervous system, inducing in humans' irreversible cognitive impairment. In this study, a cluster sampling method was used to observe the cognitive function of long-term occupational Al-exposed workers in a large Al factory, and determine the expression of peripheral blood tumour necrosis factor receptor 1 (TNFR1), receptor-interacting protein 1 (RIP1), and RIP3. TNF-alpha, expressed in blood macrophages and microglia, with its receptors TNFR1, TR1 and TR3, enhances the necroptosis of neurons. Additionally, the relationship between the expression of TNFR1, RIP1, and RIP3 in the peripheral blood of long-term occupational Al-exposed workers and changes in their cognitive function was explored. The differences in the distributions of clock drawing test (CDT) scores among the three groups were statistically significant (P < 0.05). The results of correlation analysis showed that RIP1 and RIP3 protein contents were negatively correlated with mini-mental state examination (MMSE) and CDT scores (P < 0.05). Plasma Al content was positively correlated with other biological indicators (P < 0.05), and negatively correlated with MMSE and CDT scores (P < 0.05). Results showed that RIP3 protein had an incomplete mediation effect between plasma Al content and cognitive function. This suggests that Al may affect cognitive function by influencing the expression of TNFR1, RIP1, and RIP3 in the nervous system.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130484DOI Listing
April 2021

Correction to: ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Mar 7. Epub 2021 Mar 7.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1007/s00586-021-06783-7DOI Listing
March 2021

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Feb 1. Epub 2021 Feb 1.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress.

Methods: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1β. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate.

Results: IL-1β stimulation activated NFκB demonstrating that IL-1β was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1β increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1β stimulation. hTIMP1 expression was comparable between IL-1β stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1β.

Conclusion: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.
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http://dx.doi.org/10.1007/s00586-021-06728-0DOI Listing
February 2021

Regulation of mGluR1 on the Expression of PKC and NMDAR in Aluminum-Exposed PC12 Cells.

Neurotox Res 2021 Jun 19;39(3):634-644. Epub 2021 Jan 19.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.

Aluminum demonstrates clear neurotoxicity and can cause Alzheimer's disease (AD)-like symptoms, including cognitive impairment. One toxic effect of aluminum is a decrease in synaptic plasticity, but the specific mechanism remains unclear. In this study, PC12 cells were treated with Al(mal) to construct a toxic cell model. (S)-3,5-Dihydroxyphenylglycine (DHPG), α-methyl-4-carboxyphenylglycine (MCPG), and mGluR1-siRNA were used to interfere with the expression of metabotropic glutamate receptor subtype 1 (mGluR1). Polymerase chain reaction and western blotting were used to investigate the expression of mGluR1, protein kinase C (PKC), and N-methyl-D-aspartate receptor (NMDAR) subunits. ELISA was used to detect PKC enzyme activity. In PC12 cells, mRNA and protein expressions of PKC and NMDAR subunits were inhibited by Al(mal). Aluminum may further regulate the expression of NMDAR1 and NMDAR2B through mGluR1 to regulate PKC enzyme activity, thereby affecting learning and memory functions. Furthermore, the results implied that the mGluR1-PKC-NMDAR signaling pathway may predominately involve positive regulation. These findings provide new targets for studying the neurotoxic mechanism of aluminum.
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http://dx.doi.org/10.1007/s12640-020-00319-5DOI Listing
June 2021

The GSK-3β/β-Catenin Signaling-Mediated Brain-Derived Neurotrophic Factor Pathway Is Involved in Aluminum-Induced Impairment of Hippocampal LTP In Vivo.

Biol Trace Elem Res 2021 Jan 18. Epub 2021 Jan 18.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China.

The neurotoxic effects of aluminum (Al) are associated with the impairment of synaptic plasticity, the biological basis of learning and memory, the major form of which is long-term potentiation (LTP). The canonical glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling-mediated brain-derived neurotrophic factor (BDNF) pathway has been suggested to play important roles in memory. Thus, Al may affect LTP through this pathway. In this study, a Sprague-Dawley rat model of neurotoxicity was established through intracerebroventricular (i.c.v.) injection of aluminum maltol (Al(mal)), which was achieved by preimplantation of a cannula into the lateral ventricle. The rats in the control and Al-treated groups received a daily injection of SB216763, an inhibitor of GSK-3β. Electrophysiology and western blot analysis were used to investigate the regulatory effect of the GSK-3β/β-catenin signaling-mediated BDNF pathway on LTP impairment induced by Al(mal). The results confirmed that i.c.v. injection of Al(mal) significantly suppressed the field excitatory postsynaptic potential (fEPSP) amplitude, as indicated by a decrease in BDNF protein expression, which was accompanied by dose-dependent decreases in β-catenin protein expression and the phosphorylation of GSK-3β at Ser9. Rats that received SB216763, a GSK-3β inhibitor, exhibited higher fEPSP amplitudes than control rats. Furthermore, SB216763 treatment upregulated the hippocampal protein expression of BDNF and β-catenin while increasing the ratio of p-GSK-3β/GSK-3β. From the perspective of the identified β-catenin-BDNF axis, Al impairs hippocampal LTP, possibly through the GSK-3β/β-catenin signaling-mediated BDNF pathway.
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http://dx.doi.org/10.1007/s12011-021-02582-9DOI Listing
January 2021

Effect of aluminum combined with ApoEε4 on Tau phosphorylation and Aβ deposition.

J Trace Elem Med Biol 2021 Mar 1;64:126700. Epub 2020 Dec 1.

Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, China. Electronic address:

Background: Aluminum is an environmental neurotoxin widely exposed to animals and humans. Studies have shown that Alzheimer's disease (AD) is characterized by abnormally phosphorylated tau and Aβ deposition, aluminum exposure can lead to abnormal phosphorylated tau and Aβ deposition. Numerous epidemiological data and studies have confirmed that ApoEε4 is a risk factor for AD. However, whether there is an interaction effect between aluminum and ApoEε4 has yet to be verified.

Methods: SH-SY5Y cells were exposed with AlCl and transfected with ApoEε4 respectively. The experimental groups included the blank control group, the low dose group (200 μM AlCl), the medium dose group (400 μM AlCl), the high dose group (800 μM AlCl), empty plasmid group, ApoEε4 group and 400 μM AlCl+ApoEε4 group. The cell viability was determined by CCK-8 kit after transfection for 48 h.The contents of total tau proteins, tau-181, tau-231, tau-262, tau-396 and Aβ42, were determined by ELISA kit. The interaction between AlCl and ApoEε4 was analyzed by factorial design.

Results: With the increase of aluminum exposure, SH-SY5Y cell viability decreased, and the expression of the total tau, tau-181, tau-231, tau-262, tau-396 and Aβ content increased. The viability of cells transfected with ApoEε4 is significantly lower than control group, and the expressions of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in ApoEε4 transfected cells were significantly higher than control group. The viability of cells treated with AlCl plus ApoEε4 was lower than those treated with, either AlCl, or ApoEε4. The expression of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in the cells treated with AlCl plus ApoEε4 were significantly higher than those in other groups (p < 0.05). Moreover, analyzing data based on the factorial design, there was existed an interaction between AlCl and ApoEε4 (p < 0.05).

Conclusion: Al and ApoEε4 gene can cause morphological changes of SH-SY5Y cells, reduce cell activity, and have obvious cytotoxic effects, and increase the phosphorylation levels of tau and the deposition of Aβ increases. In the presence of both Al and ApoEε4 genes, the two factors interact with each other and show a synergistic effect.
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http://dx.doi.org/10.1016/j.jtemb.2020.126700DOI Listing
March 2021

Robot-assisted orthopedic surgery in the treatment of adult degenerative scoliosis: a preliminary clinical report.

J Orthop Surg Res 2020 Jul 25;15(1):282. Epub 2020 Jul 25.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.

Study Design: A single-institution, retrospective cohort study.

Objective: To compare the accuracy and short-term clinical outcomes of pedicle screw placement between robot-assisted (RA) and freehand (FH) technique in the treatment of adult degenerative scoliosis (ADS).

Methods: From February 2018 to October 2019, 97 adult patients with degenerative scoliosis admitted to our department were retrospectively reviewed. Thirty-one patients received robot-assisted pedicle screw placement (RA group), and 66 patients underwent freehand pedicle screw placement (FH group). Patient demographics and short-term clinical outcomes were recorded and compared between two groups. Gertzbein-Robbins grading system was adopted to evaluate the accuracy of pedicle screw placement by means of postoperative CT scan. Short-term clinical outcomes consist of operative time, intraoperative blood loss, length of hospital stay (LOS), radiological parameters, Scoliosis Research Society-22 (SRS-22) scores before the operation, 6 months after operation, adverse events, and revisions.

Results: The accuracy of screw placement was higher than that of the FH group (clinically acceptable 98.7% vs. 92.2%; P< 0.001). Intraoperative blood loss of the RA group was less than those in the FH group (499 vs. 573 ml; P < 0.001). Operative time (283.1 vs. 291.9 min; P = 0.31) and length of stay (12.8 vs. 13.7 days; P = 0.36) were compared between RA and FH groups. In terms of radiological parameters, both of groups were improved postoperatively. The SRS-22 scores at 6 months after operation from both groups were better than those before operation. For surgery-related complication, one case had pressure sores in the RA group while two cases developed dural tears in the FH group. No revision was required in both groups.

Conclusion: Combined with other surgical correction modalities, robot-assisted pedicle screw fixation is an effective and safe method of treating degenerative scoliosis. Due to its satisfactory surgical outcomes such as higher accuracy and less trauma, it provides a good alternative for clinical practice.

Level Of Evidence: 3.
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http://dx.doi.org/10.1186/s13018-020-01796-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382042PMC
July 2020

Attenuation of ataxia telangiectasia mutated signalling mitigates age-associated intervertebral disc degeneration.

Aging Cell 2020 07 21;19(7):e13162. Epub 2020 Jun 21.

Ferguson Laboratory for Orthopedic and Spine Research, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

Previously, we reported that persistent DNA damage accelerates ageing of the spine, but the mechanisms behind this process are not well understood. Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the human intervertebral disc, we exposed human nucleus pulposus (hNP) cells directly to the DNA damaging agent cisplatin. Cisplatin-treated hNP cells exhibited rapid phosphorylation of ATM and subsequent increased NF-κB activation, aggrecanolysis, decreased total proteoglycan production and increased expression of markers of senescence, including p21, γH AX and SA-ß-gal. Treating cisplatin-exposed hNP cells with an ATM-specific inhibitor negated these effects. In addition, genetic reduction of ATM reduced disc cellular senescence and matrix proteoglycan loss in the progeroid Ercc1 mouse model of accelerated ageing. These findings suggest that activation of ATM signalling under persistent genotoxic stress promotes disc cellular senescence and matrix homeostatic perturbation. Thus, the ATM signalling pathway represents a therapeutic target to delay the progression of age-associated spine pathologies.
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http://dx.doi.org/10.1111/acel.13162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406969PMC
July 2020

In Vitro and In Vivo Comparison Study of Electrospun PLA and PLA/PVA/SA Fiber Membranes for Wound Healing.

Polymers (Basel) 2020 Apr 6;12(4). Epub 2020 Apr 6.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China.

Wound dressings can accelerate wound healing. The degradable polymer poly(lactic acid) (PLA) shows good mechanical properties and biocompatibility. Sodium alginate (SA) holds good biocompatibility, hemostasis, and high hygroscopicity. Poly(vinyl alcohol) (PVA) has good spinnability as a pharmaceutical excipient. Herein, we carried out a comparison study of electrospun PLA and PLA/PVA/SA fiber membranes for wound healing in vitro and in vivo. In this study, PLA and PLA/PVA/SA nanofiber membranes were fabricated through electrospinning to produce a highly porous and large specific surface area that could promote wound healing. In vitro experiments showed that PLA and PLA/PVA/SA nanofiber membranes could all provide good support for the growth of rat fibroblasts (L929). Moreover, rat fibroblasts displayed slightly better adhesion and proliferation on PLA/PVA/SA than on the PLA fiber membranes. The in vivo potentiality of the PLA and PLA/PVA/SA fiber membranes was assessed in rat models of skin defects in which the PLA and PLA/PVA/SA fiber membranes significantly improved wound healing compared to commercially available gauzes. No significant differences in wound healing were observed between PLA and PLA/PVA/SA fiber membranes in our study. Furthermore, Masson staining and PCR displayed the PLA fiber membrane promoted protein deposition compared to the PLA/PVA/SA fiber membrane. In addition, IHC suggested that PLA/PVA/SA dressing reduced the inflammatory response during early wound healing compared to the PLA fiber membrane. These findings highlight the utility of fiber membranes as novel wound-healing dressings.
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http://dx.doi.org/10.3390/polym12040839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240532PMC
April 2020

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging.

Aging (Albany NY) 2020 03 22;12(6):4688-4710. Epub 2020 Mar 22.

Department of Molecular Medicine and the Center on Aging, Scripps Research, Jupiter, FL 33458, USA.

NF-κB is a transcription factor activated in response to inflammatory, genotoxic and oxidative stress and important for driving senescence and aging. Ataxia-telangiectasia mutated (ATM) kinase, a core component of DNA damage response signaling, activates NF-κB in response to genotoxic and oxidative stress via post-translational modifications. Here we demonstrate that ATM is activated in senescent cells in culture and murine tissues from -deficient mouse models of accelerated aging, as well as naturally aged mice. Genetic and pharmacologic inhibition of ATM reduced activation of NF-κB and markers of senescence and the senescence-associated secretory phenotype (SASP) in senescent MEFs. mice heterozygous for have reduced NF-κB activity and cellular senescence, improved function of muscle-derived stem/progenetor cells (MDSPCs) and extended healthspan with reduced age-related pathology especially age-related bone and intervertebral disc pathologies. In addition, treatment of mice with the ATM inhibitor KU-55933 suppressed markers of senescence and SASP. Taken together, these results demonstrate that the ATM kinase is a major mediator of DNA damage-induced, NF-κB-mediated cellular senescence, stem cell dysfunction and aging and thus represents a therapeutic target to slow the progression of aging.
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http://dx.doi.org/10.18632/aging.102863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138542PMC
March 2020

Antinociceptive effect of intrathecal injection of miR-9-5p modified mouse bone marrow mesenchymal stem cells on a mouse model of bone cancer pain.

J Neuroinflammation 2020 Mar 16;17(1):85. Epub 2020 Mar 16.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: A growing body of studies have indicated that bone marrow mesenchymal stem cells (BMSCs) have powerful analgesic effects in animal models of bone cancer pain. Here, we explored the molecular mechanisms underlying how BMSCs alleviate pain sensation in a mouse model of bone cancer pain.

Methods: C3H/HeN adult male mice were used to generate a bone cancer pain model. BMSCs were isolated from mouse bone marrow, modified by transfection with microRNA-9-5p (miR-9-5p), and infused into the spinal cord. Spontaneous flinches, paw withdrawal latency, limb-use score, and weight-bearing score were used to assess pain-related behaviors. ELISA, RT-PCR, western blot, and luciferase assay were used to assess gene expressions.

Results: Our results show that miR-9-5p regulated the expression of both repressor element silencing transcription factor (REST) and μ-opioid receptors (MOR) by targeting REST in primary mouse BMSCs. Overexpression of miR-9-5p reversed the activation of inflammatory pathway in TNF-α- and IL-6-treated BMSCs. In addition, miR-9-5p modified BMSCs alleviated cancer pain in the sarcoma-inoculated mouse model. MiR-9-5p modified BMSCs suppressed cytokine expression in the spinal cord of sarcoma-inoculated mice by suppressing REST gene expression.

Conclusions: Our results indicate that miR-9-5p modified BMSCs can relieve bone cancer pain via modulating neuroinflammation in the central nervous system, suggesting genetically modified BMSCs could be a promising cell therapy in pain management.
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http://dx.doi.org/10.1186/s12974-020-01765-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075036PMC
March 2020

Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation.

Aging (Albany NY) 2019 11 26;11(22):10499-10512. Epub 2019 Nov 26.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

The inflammatory-associated factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine (melatonin) is a natural hormone secreted by the pineal gland which has been shown to participate in several physiological and pathological progresses, such as aging, anti-inflammation, anti-apoptosis and autophagy regulation. However, the effects of melatonin on IVD remain unclear. In the present study, we treated human nucleus pulposus cells (NPCs) with melatonin and discovered that melatonin could modulate extracellular matrix (ECM) remodeling induced by IL-1β by enhancing collagen II and aggrecan expression levels and by downregulating matrix metalloproteinase-3 (MMP-3) levels. These findings were verified by western blot and immunofluorescence assays. Intraperitoneal injection of melatonin mitigated IVDD in the rat tail puncture model. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue and Celium red staining methods were adopted to evaluate IVDD grades, the structural integrity of nucleus pulposus (NP) and annulus fibrosus (AF) and the damage and calcification of the cartilage endplate. Melatonin reduced inflammatory cell aggregation and the release of the inflammatory factors IL-1β, IL-6, TNF-α as determined by immunohistochemistry. In conclusion, the present study demonstrated that melatonin could modulate ECM remodeling by IL-1β in vitro and attenuate the IVDD and induction of inflammation in a rat tail puncture model in vivo. The data demonstrated that melatonin may contribute to the restoration processs of IVD following damage and may be used as a potential novel therapy for IVDD.
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http://dx.doi.org/10.18632/aging.102472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914432PMC
November 2019

Metformin decreases LPS-induced inflammatory response in rabbit annulus fibrosus stem/progenitor cells by blocking HMGB1 release.

Aging (Albany NY) 2019 11 26;11(22):10252-10265. Epub 2019 Nov 26.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

The present study aimed to investigate the mechanism of intervertebral disc degeneration (IVDD) and identify an efficient treatment for low back pain. Rabbit annulus fibrosus stem cells (AFSCs) were treated with metformin and lipopolysaccharide (LPS). The results indicated that LPS induced HMGB1 release from the nuclei of AFSCs and caused cell senescence in a concentration-dependent manner. The production of PGE2 and HMGB1 was increased in the medium of the LPS-treated AFSCs. Certain inflammation-associated genes (, , and α) and proteins (IL-β1, COX-2 and TNF-α) and specific catabolic genes ( and ) exhibited increased expression in LPS-treated AFSCs. However, the expression levels of other anabolic genes, such as and were decreased in LPS-treated AFSCs. Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced. The expression levels of the catabolic genes and proteins were decreased and those of the anabolic genes were increased. The findings indicated that metformin exerted an anti-inflammatory effect by blocking the HMGB1 translocation and by inhibiting catabolic production and cell senescence in AFSCs. Therefore, metformin may be used as an efficient treatment for the disc degenerative disease.
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http://dx.doi.org/10.18632/aging.102453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914423PMC
November 2019

Inflammation-dependent downregulation of miR-194-5p contributes to human intervertebral disc degeneration by targeting CUL4A and CUL4B.

J Cell Physiol 2019 11 3;234(11):19977-19989. Epub 2019 Apr 3.

Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Inflammation is one of the major causes of intervertebral disc degeneration (IDD). Emerging evidence has revealed that increase in the levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), can activate a variety of signaling pathways, eventually resulting in IDD. Here, we show that the two cullin family genes, CUL4A and CUL4B, but not other cullins, are specifically overexpressed in IDD samples compared with healthy controls, and the CUL4A and CUL4B levels are positively correlated with the severity of IDD. In vitro analyses in human osteoblast cells (hFOB1.19), nucleus pulposus cells (hNPCs), and annulus fibrosus cells (hAFCs) indicated that treatment with IL-6 and TNF-α can increase CUL4A and CUL4B levels. By performing a microRNA-based microarray analysis, we found a set of microRNAs (miRNAs) that were differentially expressed in IDD samples compared with samples from healthy controls. Of these miRNAs, miR-194-5p, was significantly downregulated in IDD samples and could bind to the three prime untranslated regions (3'-UTRs) of both CUL4A and CUL4B, thereby downregulating their expression. The in vitro overexpression or downregulation of miR-194-5p, with a miR-194-5p-mimic or with anti-miR-194-5p, can cause the repression or induction of both CUL4A and CUL4B, respectively. Interestingly, treatment with IL-6 and TNF-α inhibitors in primary hNPCs and hAFCs that were isolated from patients with IDD led to the downregulation of CUL4A and CUL4B. Together, these findings provide insight into how the inflammation-dependent downregulation of miR-194-5p contributes to the pathogenesis of IDD, which may aid in the development of new therapeutic approaches for IDD by directly targeting miR-194-5p or CUL4A and CUL4B.
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http://dx.doi.org/10.1002/jcp.28595DOI Listing
November 2019

Citrate reduced oxidative damage in stem cells by regulating cellular redox signaling pathways and represent a potential treatment for oxidative stress-induced diseases.

Redox Biol 2019 02 22;21:101057. Epub 2018 Nov 22.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, PR China; Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan 430070, PR China.

Chemical substances containing citrate such as calcium citrate, citrate esters and citric acid exhibit anti-oxidant and anti-inflammatory properties in different cells and tissues. However, data on the anti-oxidant and anti-inflammatory properties and mechanisms of action of citrate are insufficient. In this study, we systematically evaluated the anti-oxidant capacity of citrate using chemical, cellular and animal assays. Citrate showed a stable molecular structure and did not directly react with oxides. Citrate exerted protective and anti-apoptotic effects on BMSCs and also showed significant inhibitory effects on the oxidative stress and inflammatory reactions in the rat air pouch model. By using proteomics, we found that PPARγ contributed to the upregulation of various free radical scavenging proteins and the downregulation of diverse components of the inflammatory responses. Citrate-regulated global PPARγ expression was evidenced by the significant increase expression of PPARγ in PC12 cell line. Our results provide novel insights into the role of citrate in regulating cellular redox signaling and the function of PPARγ signaling in this process and also provide basic molecular cell biology information to improve the applications of biomaterials or stem cells as treatments for oxidative stress-induced degenerative diseases and inflammatory diseases.
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http://dx.doi.org/10.1016/j.redox.2018.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302140PMC
February 2019

Three-Dimensional Morphological Characteristics of Lower Lumbar Intervertebral Foramen with Age.

Biomed Res Int 2018 11;2018:8157061. Epub 2018 Nov 11.

Department of Orthopaedic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Intervertebral foramen is the doorway of nerve root and it plays an important role of radiculopathy and surgical treatment of intervertebral foramen diseases. The purpose of the study is to obtain three-dimensional (3D) morphological characteristics of lumbar intervertebral foramen and their relationship with age. Pedicle-superior articular process (P-SAP), disc height between adjacent vertebra (DH), pedicle-inferior vertebrae (P-IV), inferior posterior vertebrae-superior articular process (IPV-SAP), and bony boundary area (BBA) were measured in entrance, middle slice, and exit of lumbar intervertebral foramen for 25 males of different age groups. Spinous process to intervertebral foramen entrance (SP-IFE) was measured for 25 males of different age groups. Overall, P-SAP and P-IV decreased and IPV-SAP increased from the entrance to the exit of intervertebral foramen for L3/4-L5S1. DH decreased at entrance slice, middle slice, and exit slice for L3/4-L5S1 with age. Significant difference with aging was found only at the middle slice of L3/4 and L4/5 for P-SAP. And the significant decrease of IPV-SAP was observed at middle slice of L3/4, entrance slice of L4/5 and L5S1, and exit slice of L5S1. SP-IFE is not consistent for all subjects. In addition, the decrease of BBA at L3/4 and L4/5 was observed earlier than at L5S1. The present study described detailed information of intervertebral foramen, which may be of benefit for better understanding of the pathology and surgical planning for intervertebral foramen diseases.
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http://dx.doi.org/10.1155/2018/8157061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252236PMC
March 2019

Electrospun preparation and biological properties in vitro of polyvinyl alcohol/sodium alginate/nano-hydroxyapatite composite fiber membrane.

Colloids Surf B Biointerfaces 2019 Jan 29;173:171-177. Epub 2018 Sep 29.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, PR China.

The composite fiber membrane of polyvinyl alcohol (PVA)/sodium alginate (SA)/nano-hydroxyapatite (nHAP) was fabricated by electrospinning method. In order to prevent the agglomeration and precipitation of nHAP in aqueous spinning solution, nHAP was ultrasonically suspended in aqueous solution using SA (the component of composite membrane) as stabilizer. The effect of nHAP on the morphology and mechanical property of composite fiber membrane was investigated. The in vitro biological properties including hemolysis, cytotoxicity, cell adhereing and proliferation of composite fiber membrane were evaluated. Results show that SA stabilized nHAP (SA-nHAP) suspension (1.67-10.02 mg/mL) can be obtained with SA/nHAP mass ratio of 1:33.4 for preparing homogeneous spinning solution. The electrospun membranes with PVA/SA/nHAP mass ratio of 9.33:(0.67-0.69):(0-0.668) show good fiber morphology, homogeneous incorporation and distribution of nHAP in fibers, and the content of SA-nHAP (6.25 wt%) in membrane is significantly increased compared to that of untreated nHAP (3.23 wt%). The incorporation of SA-nHAP of 1.64 wt.% significantly improves the tensile strength of PVA/SA/nHAP fiber membrane with about 45% enhancement. The hemolysis and cytotoxicity tests show that the composite fiber membrane has good biocompatibility. Moreover, cells can be seeded and proliferate well on composite fiber membrane. Therefore, the obtained PVA/SA/nHAP composite fiber membrane has the potential use as a tissue regeneration material.
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http://dx.doi.org/10.1016/j.colsurfb.2018.09.074DOI Listing
January 2019

Recovery of respiratory function and autonomic diaphragm movement following unilateral recurrent laryngeal nerve to phrenic nerve anastomosis in rabbits.

J Neurosurg Spine 2018 Oct 6;29(4):470-480. Epub 2018 Jul 6.

Departments of3Spine Surgery and.

The authors studied restoration of respiratory function in rabbits, using the recurrent laryngeal nerve to restore function after the phrenic nerve had been severed. The results of this animal study are encouraging and suggest that a similar technique could possibly be used to help patients with severe cervical spinal cord injuries.
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http://dx.doi.org/10.3171/2017.12.SPINE17849DOI Listing
October 2018

The Biomechanical Study of Extraforaminal Lumbar Interbody Fusion: A Three-Dimensional Finite-Element Analysis.

J Healthc Eng 2017 26;2017:9365068. Epub 2017 Sep 26.

Department of Spine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China.

Objective: Finite-element method was used to evaluate biomechanics stability of extraforaminal lumbar interbody fusion (ELIF) under different internal fixation.

Methods: The L3-L5 level finite-element model was established to simulate decompression and internal fixation at L4-L5 segment. The intact finite model was treated in accordance with the different internal fixation. The treatment groups were exerted 400 N load and 6 N·m additional force from motion to calculate the angular displacement of L4-L5.

Results: The ROMs were smaller in all internal fixation groups than those in the intact model. Furthermore, the ROMs were smaller in ELIF + UPS group than in TLIF + UPS group under all operating conditions, especially left lateral flexion and right rotation. The ROMs were higher in ELIF + UPS group than in TLIF + BPS group. The ROMs of ELIF + UPS + TLFS group were much smaller than those in ELIF + UPS group, and as compared with TLIF + BPS group, there was no significant difference in the range of experimental loading.

Discussion: The biomechanical stability of ELIF with unilateral pedicle screw fixation is superior to that of TLIF with unilateral pedicle screw fixation but lower than that of TLIF with bilateral pedicle screws fixation. The stability of ELIF with unilateral fixation can be further improved by supplementing a translaminar facet screw.
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http://dx.doi.org/10.1155/2017/9365068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634568PMC
July 2019

Ultrasonically assisted preparation of poly(acrylic acid)/calcium phosphate hybrid nanogels as pH-responsive drug carriers.

Mater Sci Eng C Mater Biol Appl 2017 Nov 18;80:688-697. Epub 2017 Jul 18.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, PR China.

Biocompatible, biodegradable and stimuli-responsive nanomaterials can be used as drug carriers and to achieve controlled drug delivery, which is crucial for treating tumors and lowering drug side effects. Calcium phosphate (CaP) nanoparticles and poly(acrylic acid) (PAA) hydrogels can be used as biocompatible and pH-responsive drug carriers. In this study, based on the ultrasound effect, PAA/CaP hybrid nanogels (approximately 100nm, PDI<0.2) are obtained via the cross-linking of CaP nanoparticles and PAA molecules between the Ca ions and -COOH groups. The PAA/CaP hybrid nanogels show good stability in biological media as well as no hemolysis and no cytotoxicity to L02 cells. Moreover, the PAA/CaP hybrid nanogels display an enhanced loading capacity (approximately 32%) for doxorubicin hydrochloride (DOX) compared to pure CaP nanoparticles (approximately 7.5%) and a pH-controlled drug release due to their dissolution in acidic environment. DOX can be delivered into cancer cells by the PAA/CaP hybrid nanogels, which show an inhibitory effect comparable to that of free DOX, although the inhibitory effect is delayed due to the slow release of DOX from the carriers. In vivo, the PAA/CaP hybrid nanogels cannot avoid the capture by the reticuloendothelial system; however, they show passive tumor targeting ability. In brief, the biocompatible, biodegradable and pH-responsive PAA/CaP hybrid nanogels have the potential to act as drug carriers for controlled drug release.
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http://dx.doi.org/10.1016/j.msec.2017.07.022DOI Listing
November 2017

Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation.

Sci Rep 2017 08 7;7(1):7403. Epub 2017 Aug 7.

Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai, 200120, China.

Epidemiological studies have concluded that hyperlipidemia and atherosclerosis were related to intervertebral disc degeneration (IVDD). The presence of oxidized low density lipoprotein (ox-LDL) and the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) have not been explored in this tissue. In this study, we investigated the presence of ox-LDL and the expression of its receptor LOX-1 in non-degenerated, degenerated or herniated human intervertebral discs (IVDs). The expression of LOX-1 and matrix metalloproteinase 3 (MMP3) were studied after incubating nucleus pulposus cells (NPCs) with ox-LDL. The presence of ox-LDL and LOX-1 was positively related with the extent of IVDD in nucleus pulposus (NP), end-plate cartilage and outer annulus fibrous, but not with the extent of degeneration of inter annulus fibrous. Ox-LDL significantly reduced the viability of human NPCs in a dose and time-dependent manner, and increased the expression of MMP3 induced by LOX-1. Pretreatment with anti-human LOX-1 monoclonal antibody reversed these effects. Ox-LDL, principally mediated by LOX-1, enhanced MMP3 production in NPCs through the NF-κB signaling pathway. In conclusion, increased accumulation of ox-LDL and LOX-1 in IVDs indicates a specific role of the receptor-ligand interaction in degeneration or herniation of IVDs.
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http://dx.doi.org/10.1038/s41598-017-07780-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547039PMC
August 2017

Significance of preoperative planning software for puncture and channel establishment in percutaneous endoscopic lumbar DISCECTOMY: A study of 40 cases.

Int J Surg 2017 May 23;41:97-103. Epub 2017 Mar 23.

Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China. Electronic address:

Background: Preoperative planning software has been widely used in many other minimally invasive surgeries, but there is a lack of information describing the clinical benefits of existing software applied in percutaneous endoscopic lumbar discectomy (PELD). This study aimed to compare the clinical efficacy of preoperative planning software in puncture and channel establishment of PELD with routine methods in treating lumbar disc herniation (LDH).

Material And Methods: From June 2016 to October 2016, 40 patients who had single L4/5 or L5/S1 disc herniation were divided into two groups. Group A adopted planning software for preoperative puncture simulation while Group B took routine cases discussion for making puncture plans. The channel establishment time, operative time, fluoroscopic times and complications were compared between the two groups. The surgical efficacy was evaluated according to the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and modified Macnab's criteria.

Results: The mean channel establishment time was 25.1 ± 4.2 min and 34.6 ± 5.4 min in Group A and B, respectively (P < 0.05). The mean operative time was 80.8 ± 8.4 min and 92.1 ± 7.3 min in Group A and B, respectively (P < 0.05). The fluoroscopic times were 21.5 ± 5.2 in Group A and 29.3 ± 5.5 in Group B (P < 0.05). There were no significant differences in VAS and ODI scorings between the two groups either preoperatively or postoperatively (P > 0.05). The findings of modified Macnab's criteria at each follow-up also showed no significant differences (P > 0.05).

Conclusion: The application of preoperative planning software in puncture and cannula insertion planning in PELD was easy and reliable, and could reduce the channel establishment time, operative time and fluoroscopic times of PELD significantly.
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http://dx.doi.org/10.1016/j.ijsu.2017.03.059DOI Listing
May 2017

Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration.

Biochem Biophys Res Commun 2019 08 23;516(3):1026-1032. Epub 2017 Mar 23.

Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School of Medicine, 150 Jimo Road, Shanghai 200120, China.

Cartilage endplate (CEP) cell calcification and apoptosis play a vital role in the intervertebral disc degeneration (IVDD). Oxidative stress is a key factor in inducing programmed cell death and cartilage calcification. However, the cell death and calcification of cartilage endplate cells under oxidative stress have never been described. The present study investigated the apoptosis and calcification in the cartilage endplate cell under oxidative stress induced by HO to understand the underlying mechanism of IVDD. The cartilage endplate cells isolated from human lumbar discs were subjected to different concentrations of HO for various time periods. The cell viability was determined by CCK-8 assay, whereas Western blot, immunofluorescence, and Alcian blue, Alizarin red, and Von Kossa staining evaluated the apoptosis and calcification. The level of mitochondria-specific reactive oxygen species (ROS) was quantified with an oxygen radical-sensitive probe-MitoSOX. The potential signaling pathways were investigated by Western blot after the addition of N-acetyl-l-cysteine (NAC). We found that the oxidative stress induced by HO increased the apoptosis and subsequently the calcification in the cartilage endplate cells through the ROS/p38/ERK/p65 pathway. The apoptosis and the calcification of the cartilage endplate cells induced by HO can be abolished by NAC. These results suggested that regulating the apoptosis and the calcification in the cartilage endplate cells under oxidative stress should be advantageous for the survival of cells and might delay the process of disc degeneration.
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http://dx.doi.org/10.1016/j.bbrc.2017.03.111DOI Listing
August 2019

A Biomechanical Stability Study of Extraforaminal Lumbar Interbody Fusion on the Cadaveric Lumbar Spine Specimens.

PLoS One 2016 22;11(12):e0168498. Epub 2016 Dec 22.

Department of Spine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Transforaminal lumbar interbody fusion (TLIF) is an effective surgery for lumbar degenerative disease. However, this fusion technique requires resection of inferior facet joint to provide access for superior facet joint resection, which results in reduced lumbar spinal stability and unnecessary trauma. We have previously developed extraforaminal lumbar interbody fusion (ELIF) that can avoid back muscle injury with direct nerve root decompression. This study aims to show that ELIF enhances lumbar spinal stability in comparison to TLIF by comparing lumbar spinal stability of L4-L5 range of motion (ROM) on 12 cadaveric spine specimens after performing TLIF or ELIF.

Methods: 12 cadaveric spine specimens were randomly divided and treated in accordance with the different internal fixations, including ELIF with a unilateral pedicle screw (ELIF+UPS), TLIF with a unilateral pedicle screw (TLIF+UPS), TLIF with a bilateral pedicle screw (TLIF+BPS), ELIF with a unilateral pedicle screw and translaminar facet screw (ELIF+UPS+TLFS) and ELIF with a bilateral pedicle screw (ELIF+BPS). The treatment groups were exposed to a 400-N load and 6 N·m movement force to calculate the angular displacement of L4-L5 during anterior flexion, posterior extension, lateral flexion and rotation operation conditions.

Results: The ROM in ELIF+UPS group was smaller than that of TLIF+UPS group under all operating conditions, with the significant differences in left lateral flexion and right rotation by 36.15% and 25.97% respectively. The ROM in ELIF+UPS group was higher than that in TLIF+BPS group. The ROM in the ELIF+UPS+TLFS group was much smaller than that in the ELIF+UPS group, but was not significantly different than that in the TLIF+BPS group.

Conclusions: Despite that TLIF+BPS has great stability, which can be comparable by that of ELIF+UPS. Additionally, ELIF stability can be further improved by using translaminar facet screws without causing more tissue damage to patient.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168498PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178989PMC
July 2017

Leptin induces osteocalcin expression in ATDC5 cells through activation of the MAPK-ERK1/2 signaling pathway.

Oncotarget 2016 Sep;7(39):64021-64029

Department of Spine Surgery, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai, 200120, China.

Both leptin and osteocalcin have been found to affect growth-plate cartilage development through regulation of the physiologic processes of endochondral bone formation. Leptin mediates bone development and osteocalcin secreted in the late stage of osteoblast differentiation. The relationship between leptin and osteocalcin expression in the chondrogenic cells line is still not clear. Thus, the aim of this study was to explore the effect of leptin on the expression of osteocalcin in chondrocytes. We used clonal mouse chondrogenic ATDC5 cells to investigate the relationship between leptin and osteocalcin. We found that both leptin and osteocalcin expression were dynamically expressed during ATDC5 cell differentiation from 4 to 21 days. We also found that leptin significantly upregulated osteocalcin mRNA and protein levels 24 h after leptin stimulation. However, different concentrations and exposure times of osteocalcin did not affect the levels of leptin protein. Furthermore, we confirmed that leptin augmented the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in a time-dependent manner but not p38 or AKT. Inhibition of pERK1/2 expression by a specific ERK1/2 inhibitor U0126 and a special small interfering RNA attenuated levels of leptin-induced osteocalcin expression, indicating that ERK1/2 mediates, in part, the effects of leptin on osteocalcin. Taken together, our results suggest that leptin regulates the expression of osteocalcin in growth plate chondrocytes via the ERK1/2 signaling pathway, while there is no effect on the phosphorylation of either p38 or AKT.
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http://dx.doi.org/10.18632/oncotarget.11578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325422PMC
September 2016

Percutaneous endoscopic lumbar discectomy for lumbar disc herniation.

J Clin Neurosci 2016 Nov 27;33:19-27. Epub 2016 Jul 27.

Department of Spinal Surgery, East Hospital, Tongji University School of Medicine, 150 JiMo Road, Shanghai 200120, China. Electronic address:

This study aims to compare the advantages and disadvantage of percutaneous endoscopic lumbar discectomy (PELD) and standard discectomy (SD) for the treatment of lumbar intervertebral disc herniation (LDH). We searched in MEDLINE, EMBASE, PubMed, Web of Science and Cochrane databases for relevant trials that compare PELD and SD for the treatment of LDH. The Cochrane Collaboration's Revman 5.3 software was used for data analyses. This meta-analysis compiled 1301 cases from four random controlled trials and three retrospective studies. Compared with SD, PELD showed a shorter operative time (mean difference (MD)=-18.68, 95% confidence interval (CI): -24.92 to -12.43; p<0.00001), less blood loss (MD=-64.88, 95% CI: -114.51 to -15.25, p<0.0001), shorter hospital stay (MD=-3.51, 95% CI: -4.93 to -2.08, p<0.00001), and shorter mean disability period (MD=-34.34, 95% CI: -53.90 to -14.77, p<0.006). However, there were no significant differences in the visual analogue scale (VAS) scores at the final follow up (MD=-0.23, 95% CI: -0.53 to 0.07, p=0.14), Macnab criteria at the final follow up (MD=1.04, 95% CI: 0.72 to 1.50, p=0.82), complications (RR=0.76, 95% CI: 0.40 to 1.43, p=0.39), recurrence rate (risk ratio (RR)=1.00, 95% CI: 0.61 to 1.64, p=1) and reoperation rate (RR=1.40, 95% CI: 0.90 to 2.16, p=0.13). In conclusion, despite PELD showing significant benefit in short term outcomes such as hospital course and mean disability period, similar clinical efficacy and long term outcomes were observed when compared to SD. Therefore, we suggest that PELD can be a feasible alternative to the conventional posterior approach for the LDH depending on surgeon preference and indication. High-quality randomized controlled trials with sufficient large sample sizes necessary further confirm these results.
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http://dx.doi.org/10.1016/j.jocn.2016.01.043DOI Listing
November 2016

Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as Imaging Agents In Vitro and In Vivo.

ACS Appl Mater Interfaces 2016 04 13;8(16):10212-9. Epub 2016 Apr 13.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology , Wuhan 430070, P. R. China.

Biocompatible, biodegradable, and luminescent nano material can be used as an alternative bioimaging agent for early cancer diagnosis, which is crucial to achieve successful treatment. Hydroxyapatite (HAP) nanocyrstals have good biocompatibility and biodegradability, and can be used as an excellent host for luminescent rare earth elements. In this study, based on the energy transfer from Gd(3+) to Eu(3+), the luminescence enhanced imaging agent of Eu/Gd codoping HAP (HAP:Eu/Gd) nanocrystals are obtained via coprecipitation with plate-like shape and no change in crystal phase composition. The luminescence can be much elevated (up to about 120%) with a nonlinear increase versus Gd doping content, which is due to the energy transfer ((6)PJ of Gd(3+) → (5)HJ of Eu(3+)) under 273 nm and the possible combination effect of the cooperative upconversion and the successive energy transfer under 394 nm, respectively. Results demonstrate that the biocompatible HAP:Eu/Gd nanocrystals can successfully perform cell labeling and in vivo imaging. The intracellular HAP:Eu/Gd nanocrystals display good biodegradability with a cumulative degradation of about 65% after 72 h. This biocompatible, biodegradable, and luminescence enhanced HAP:Eu/Gd nanocrystal has the potential to act as a fluorescent imaging agent in vitro and in vivo.
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http://dx.doi.org/10.1021/acsami.6b01814DOI Listing
April 2016

Percutaneous endoscopic lumbar discectomy for recurrent lumbar disc herniation.

Int J Surg 2016 Mar 22;27:8-16. Epub 2016 Jan 22.

Department of Spinal Surgery, East Hospital, Tongji University, School of Medicine, 150 JiMo Road, Shanghai 200120, China.

The objective of this systematic review was to identify the effectiveness of percutaneous endoscopic lumbar discectomy (PELD) in the treatment of recurrent lumbar disc herniation (rLDH) and to present its indications and techniques. We conducted a comprehensive search in MEDLINE, EMBASE, PubMed, Web of Science and Cochrane databases, searching for relevant studies of managing rLDH with PELD up to July 2015. Only papers published in English were included. Two review authors independently selected the studies, extracted relevant data and assessed their methodological quality. The Cochrane Collaboration's Revman 5.3 software was used for data analyses among the controlled studies. At last, one randomized controlled trial (RCT), two non-randomized control studies and five observational studies including a total of 579 cases were selected for this system review. The methodological quality of these studies was low to modern. The mean overall improvement of leg pain (visual analogue scale) was 66.92% (50.6%-89.87%), back pain (visual analogue scale) 54.91% (29%-67.95%), Oswestry Disability Index 60.9% (40.7%-75%), global perceived effect (MacNab/other) 75.77% (60%-95%). The mean overall of complication rate was 4.89% (0%-9.76%), dural tear rate 0.1% (0%-4.9%), recurrence rate 6.3% (4%-10%), re-operation rate 3.66% (2.33%-4.8%). We conducted a meta-analysis among the control trials. Compared with Open discectomy (OD), PELD resulted in better outcomes in terms of operative time, blood loss, lower complication rates, but with no significance differences regarding hospital stay, second recurrence rate, Macnab criteria and pain reduction. In conclusion, according to the current evidence, PELD is an effective procedure for the treatment of rLDH in terms of reducing complication and shorting hospital course, comparing with OD. Therefore, we suggested that PELD was a feasible alternative to OD in the treatment of the rLDH in the condition of proper indication. High-quality RCTs with large sample sizes are needed to further confirm these results.
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http://dx.doi.org/10.1016/j.ijsu.2016.01.034DOI Listing
March 2016