Publications by authors named "Xijing He"

138 Publications

Accuracy of cervical pedicle screw placement with four different designs of rapid prototyping navigation templates: a human cadaveric study.

Comput Assist Surg (Abingdon) 2021 Dec;26(1):49-57

Department of Orthopedics, Xi'an Jiaotong University Second Affiliated Hospital, Xincheng District, Shannxi, People's Republic of China.

Purpose: Due to the high perforation rate of cervical pedicle screw placement, we have designed four different types of rapid prototyping navigation templates to enhance the accuracy of cervical pedicle screw placement.

Methods: Fifteen human cadaveric cervical spines from C2 to C7 were randomly divided into five groups, with three specimens in each group. The diameter of pedicle screw used in this study was 3.5 mm. Groups 1-4 were assisted by the two-level template, one-level bilateral template, one-level unilateral template and one-level point-contact template, respectively. Group 5 was without any navigation template. After the surgery, the accuracy of screw placement in the five groups was evaluated using postoperative computed tomographic scans to observe whether the screw breached the pedicle cortex.

Results: A total of 180 pedicle screws were inserted without any accidents. The accuracy rate was 75%, 100%, 100%, 91.7%, and 63.9%, respectively, from Groups 1 to 5. All the template groups were significantly higher than Group 5, though the two-level navigation template group was significantly lower than the other three template groups. The operation time was 4.72 ± 0.28, 4.81 ± 0.29, 5.03 ± 0.35, 8.42 ± 0.36, and 10.05 ± 0.52 min, respectively, from Groups 1 to 5. The no template and point-contact procedures were significantly more time-consuming than the template procedures.

Conclusion: This study demonstrated that four different design types of navigation templates achieved a higher accuracy in assisting cervical pedicle screw placement than no template insertion. However, the two-level template's accuracy was the lowest compared to the other three templates. Meanwhile, these templates avoided fluoroscopy during the surgery and decreased the operation time. It is always very challenging to translate cadaveric studies to clinical practice. Hence, the one-level bilateral, unilateral, and point-contact navigation templates designed by us need to be meticulously tested to verify their accuracy and safety.
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http://dx.doi.org/10.1080/24699322.2021.1919210DOI Listing
December 2021

Chemogenetic stimulation of proprioceptors remodels lumbar interneuron excitability and promotes motor recovery after SCI.

Mol Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Department of Orthopedics, Xi'an International Medical Center, Xi'an, Shaanxi 710075, China. Electronic address:

Motor recovery after severe spinal cord injury (SCI) is limited due to the disruption of direct descending commands. Despite the absence of brain-derived descending inputs, sensory afferents below injury sites remain intact. Among them, proprioception acts as an important sensory source to modulate local spinal circuits and determine motor outputs. Yet, it remains unclear whether enhancing proprioceptive inputs promotes motor recovery after severe SCI. Here, we first established a viral system to selectively target lumbar proprioceptive neurons and then introduced the excitatory Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus into proprioceptors to achieve specific activation of lumbar proprioceptive neurons upon CNO administration. We demonstrated that chronic activation of lumbar proprioceptive neurons promoted the recovery of hindlimb stepping ability in a bilateral hemisection SCI mouse model. We further revealed that chemogenetic proprioceptive stimulation led to coordinated activation of proprioception-receptive spinal interneurons and facilitated transmission of supraspinal commands to lumbar motor neurons, without affecting the regrowth of proprioceptive afferents or brain-derived descending axons. Moreover, application of 4-aminopyridine-3-methanol (4-AP-MeOH) that enhances nerve conductance further improved the transmission of supraspinal inputs and motor recovery in proprioception-stimulated mice. Our study demonstrates that proprioception-based combinatorial modality may be a promising strategy to restore the motor function after severe SCI.
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http://dx.doi.org/10.1016/j.ymthe.2021.04.023DOI Listing
April 2021

Myelin Debris Stimulates NG2/CSPG4 Expression in Bone Marrow-Derived Macrophages in the Injured Spinal Cord.

Front Cell Neurosci 2021 19;15:651827. Epub 2021 Mar 19.

Department of Immunology, Guizhou Medical University, Guiyang, China.

Although the increased expression of members of the chondroitin sulfate proteoglycan family, such as neuron-glial antigen 2 (NG2), have been well documented after an injury to the spinal cord, a complete picture as to the cellular origins and function of this NG2 expression has yet to be made. Using a spinal cord injury (SCI) mouse model, we describe that some infiltrated bone marrow-derived macrophages (BMDMΦ) are early contributors to NG2/CSPG4 expression and secretion after SCI. We demonstrate for the first time that a lesion-related form of cellular debris generated from damaged myelin sheaths can increase NG2/CSPG4 expression in BMDMΦ, which then exhibit enhanced proliferation and decreased phagocytic capacity. These results suggest that BMDMΦ may play a much more nuanced role in secondary spinal cord injury than previously thought, including acting as early contributors to the NG2 component of the glial scar.
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http://dx.doi.org/10.3389/fncel.2021.651827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017290PMC
March 2021

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Hum Exp Toxicol 2021 Mar 29:9603271211003311. Epub 2021 Mar 29.

Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.
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http://dx.doi.org/10.1177/09603271211003311DOI Listing
March 2021

Application of ultrasound during electrode implantation for sacral neuromodulation in patients with neurogenic bladder secondary to spinal cord disease: a retrospective study.

Int Urol Nephrol 2021 Jul 20;53(7):1325-1330. Epub 2021 Mar 20.

Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.

Purpose: To compare the use of intraoperative ultrasound with X-ray fluoroscopy during sacral neuromodulation lead electrode placement in patients with neurogenic bladder secondary to spinal cord disease.

Methods: We reviewed the medical records of 52 patients who underwent sacral neuromodulation (SNM) lead electrode implantation under fluoroscopy or ultrasound guidance from July 2016 to July 2019. The operating time, number of electrode contacts with stimulus responses, minimum voltage that causes a stimulus response, and rate of standard lead electrode placement were used to assess the differences between the two methods. All patients were evaluated by recording bladder diaries, postvoid residual volumes before and during the testing period. Permanent SNM implantation is acceptable if symptoms improve by at least 50%.

Results: The operating time decreased from 87.1 ± 25.19 min in the X-ray group to 68.2 ± 25.20 min (p < 0.05) in the ultrasound group. The number of electrode contacts with stimulus responses, rate of standard lead electrode placement, and implantable pulse generator (IPG) placement rate were not significantly different between the two groups (p > 0.05). There was no radiation exposure during the operation in the ultrasound group. No incisional infections, hematomas, or other critical complications were reported in either groups.

Conclusion: Ultrasound can be applied to safely place lead electrode for sacral neuromodulation and leads to no radiation exposure to the patient, surgeon, and operating room staff and a shortened operating time while maintaining the same efficacy as X-ray.
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http://dx.doi.org/10.1007/s11255-021-02824-8DOI Listing
July 2021

Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury.

J Mol Histol 2021 Apr 6;52(2):301-311. Epub 2021 Feb 6.

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.

Stem cell transplantation is a promising method in the treatment of spinal cord injury (SCI). Researches have shown that stem cell-derived exosomes as well as its contents such as microRNAs contribute to the protective effects of stem cell against SCI. However, the effects of exosomes derived from bone marrow stem cells on SCI and the underlying mechanisms remain unknown. In this study, we collected bone marrow stem cells derived exosomes (BMSCs-exo) to deal with SCI rats and LPS induced microglia to explore the possible mechanisms. We found that BMSCs-exo showed significant effects on decreasing pro-inflammatory cytokines as well as increasing Basso-Beattie-Bresnahan score after acute SCI. MicroRNA-181c levels in tissue were elevated with the use of BMSCs-exo. Then we verified the effect in vitro and found that in LPS induced microglia, the administration of BMSCs-exo could inhibit the expression of pro-inflammatory cytokines, and the phosphorylation of NF-κB signal was also suppressed. During which, the expression of microRNA-181c in microglia was elevated. When LPS induced microglia were treated with BMSCs-exo over-expressing microRNA-181c, the levels of pro-inflammatory cytokines decreased. Then bioinformatics techniques were used to detect the possible target gene of microRNA-181c and then PTEN was found as a candidate. Further experiments showed that the protection effects of BMSCs-exo over-expressing microRNA-181c could be antagonized by the elevation of PTEN expression both in vitro and in vivo. In conclusion, we verified that BMSCs-exo could protect against SCI through its content microRNA-181c which suppressed the inflammation in microglia and spinal cord. It was related to the inhibition of PTEN and the suppression of NF-κB signal, and finally decreasing inflammation and apoptosis in spinal cord and improved SCI.
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http://dx.doi.org/10.1007/s10735-020-09950-0DOI Listing
April 2021

Biomechanical properties of a novel nonfusion artificial vertebral body for anterior lumbar vertebra resection and internal fixation.

Sci Rep 2021 Jan 29;11(1):2632. Epub 2021 Jan 29.

Department of Spine and Spinal Cord Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou Umiversity, Zhengzhou, 450003, China.

The aim of the study was to evaluate the biomechanical properties of a novel nonfused artificial vertebral body in treating lumbar diseases and to compare with those of the fusion artificial vertebral body. An intact finite element model of the L1-L5 lumbar spine was constructed and validated. Then, the finite element models of the fusion group and nonfusion group were constructed by replacing the L3 vertebral body and adjacent intervertebral discs with prostheses. For all finite element models, an axial preload of 500 N and another 10 N m imposed on the superior surface of L1. The range of motion and stress peaks in the adjacent discs, endplates, and facet joints were compared among the three groups. The ranges of motion of the L1-2 and L4-5 discs in flexion, extension, left lateral bending, right lateral bending, left rotation and right rotation were greater in the fusion group than those in the intact group and nonfusion group. The fusion group induced the greatest stress peaks in the adjacent discs and adjacent facet joints compared to the intact group and nonfusion group. The nonfused artificial vertebral body could better retain mobility of the surgical site after implantation (3.6°-8.7°), avoid increased mobility and stress of the adjacent discs and facet joints.
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http://dx.doi.org/10.1038/s41598-021-82086-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846776PMC
January 2021

MicroRNA-137-mediated lysine demethylase 4A regulates the recovery of spinal cord injury via the SFRP4-Wnt/β-Catenin axis.

Int J Neurosci 2021 Feb 8:1-14. Epub 2021 Feb 8.

Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.

Objective: Spinal cord injury (SCI) causes great harm to the normal life of patients. Histone demethylase is involved in many biological processes, including SCI. Hence, this study explored the role and mechanism of histone lysine demethylase 4A (KDM4A) in SCI.

Methods: The acute SCI (ASCI) rat model was established after spinal compression and the SCI neuronal model was induced treating PC12 cells with lipopolysaccharide (LPS). KDM4A expression during SCI was detected. The microRNA (miRNA) targeting KDM4A was predicted and verified. The miRNA and KDM4A expression patterns were intervened in LPS-stimulated PC12 cells to evaluate their combined effects on neuronal cells in SCI. The downstream pathways of KDM4A were predicted, and SFRP4 and H3K9me3 expressions were determined. After the intervention of SFRP4 in LPS-treated cells, β-Catenin expression and the effect of SFRP4 on neuronal cells in SCI were detected. Finally, the effectiveness of the miR-137/KDM4A/SFRP4/Wnt/β-Catenin axis was verified .

Results: KDM4A was abnormally elevated in SCI. miR-137 targeted KDM4A. miR-137 effectively inhibited the apoptosis of LPS-challenged PC12 cells, which could be reversed after overexpressing KDM4A. KDM4A promoted SFRP4 expression through demethylation of H3K9me3. Overexpression of SFRP4 blocked the Wnt/β-Catenin pathway and promoted apoptosis of LPS-stimulated cells. , miR-137 overexpression remarkably improved SCI symptoms, accompanied by obviously increased β-Catenin expression and notably decreased KDM4A and SFRP4 expressions, while overexpressed KDM4A treatment showed the opposite trend in the presence of miR-137.

Conclusion: We demonstrated that miR-137 targeted KDM4A and then downregulated SFRP4 to ameliorate SCI in a Wnt/β-Catenin-dependent manner.
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http://dx.doi.org/10.1080/00207454.2021.1881093DOI Listing
February 2021

Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis.

Cell Tissue Res 2021 May 19;384(2):301-312. Epub 2021 Jan 19.

Department of Orthopaedics, the Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, No. 157, Xiwu Road, Xi'an, 710004, China.

Spinal cord injury (SCI) is a major cause of paralysis, disability and even death in severe cases. Lithium has neuroprotective effects on SCI, while the underlying mechanisms remain obscure. In the present study, we established a SCI rat model, which subsequently received lithium treatment. Results displayed that lithium treatment improved the locomotor function recovery and reduced apoptosis by increasing anti-apoptotic molecule expression and decreasing pro-apoptotic factor expression in SCI rats. Furthermore, lithium treatment alleviated the inflammatory response by inactivating the nuclear factor-kappa B (NF-κB) pathway and inhibited the expression of lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) in SCI rats. Subsequent researches indicated that miR-9-5p was targeted and regulated by BDNF-AS. Lithium treatment rescued the upregulation of BDNF-AS expression and downregulation of miR-9-5p expression induced by HO in SH-SY5Y cells. BDNF-AS overexpression or miR-9-5p interference attenuated the anti-apoptotic and anti-inflammatory effects of lithium chloride in SH-SY5Y cells that was damaged by HO induction, revealing that lithium might act through the BDNF-AS/miR-9-5p axis. In vivo studies showed that the injection of BDNF-AS adenovirus vector or miR-9-5p inhibitor reversed the effects of lithium on the histologic morphology of spinal cord, motor function, inflammatory reaction and apoptosis in SCI rats, which was consistent with the results of in vitro studies. In conclusion, our data demonstrated that lithium reduced SCI-induced apoptosis and inflammation in rats via the BDNF-AS/miR-9-5p axis.
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http://dx.doi.org/10.1007/s00441-020-03298-3DOI Listing
May 2021

Common variants in MAEA gene contributed the susceptibility to osteoporosis in Han Chinese postmenopausal women.

J Orthop Surg Res 2021 Jan 10;16(1):38. Epub 2021 Jan 10.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, China.

Background: Osteoporosis (OP) is a complex bone metabolism disorder characterized by the loss of bone minerals and an increased risk of bone fracture. A recent study reported the relationship of the macrophage erythroblast attacher gene (MAEA) with low bone mineral density in postmenopausal Japanese women. Our study aimed to investigate the association of MAEA with postmenopausal osteoporosis (PMOP) in Han Chinese individuals.

Methods: A total of 968 unrelated postmenopausal Chinese women comprising 484 patients with PMOP and 484 controls were recruited. Four tag single nucleotide polymorphisms (SNPs) that covered the gene region of MAEA were chosen for genotyping. Single SNP and haplotypic association analyses were performed, and analysis of variance was conducted to test the correlation between blood MAEA protein level and genotypes of associated SNPs.

Results: SNP rs6815464 was significantly associated with the risk of PMOP. The C allele of rs6815464 was strongly correlated with the decreased risk of PMOP in our study subjects (OR[95% CI]=0.75[0.63-0.89], P=0.0015). Significant differences in MAEA protein blood levels among genotypes of SNP rs6815464 were identified in both the PMOP (F=6.82, P=0.0012) and control groups (F=11.5, P=0.00001). The C allele was positively associated with decreased MAEA protein levels in blood.

Conclusion: This case-control study on Chinese postmenopausal women suggested an association between SNP rs6815464 of MAEA and PMOP. Further analyses showed that genotypes of SNP rs6815464 were also associated with the blood level of MAEA protein.
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http://dx.doi.org/10.1186/s13018-020-02140-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798333PMC
January 2021

Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway.

J Cell Mol Med 2021 Feb 21;25(4):2148-2162. Epub 2020 Dec 21.

Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

microRNA-126 (miR-126), an endothelial-specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR-126-based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR-126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR-126 (Exo-miR-126) by ultracentrifugation. In vitro study, Exo-miR-126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis-related vascular endothelial growth factor (VEGF) and angiotensin-1 (Ang-1) were up-regulated after incubation with Exo-miR-126. Additionally, the expression level of phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR-126 in HUVECs. Particularly, the Exo-miR-126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo-miR-126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR-126 may be a promising strategy to promote angiogenesis.
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http://dx.doi.org/10.1111/jcmm.16192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882955PMC
February 2021

β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund's adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway.

Drug Deliv 2020 Dec;27(1):1329-1341

Department of Pathology, Xi'an Fourth Hospital, Xi'an, China.

Rheumatoid arthritis (RA), autoimmune disease that is categorized via chronic inflammation manifestation, obesity, cardiovascular risk and even enhanced the mortality and affect the 0.3 and 1% of population worldwide. The current experimental study was scrutinize the anti-arthritic effect of β-sitosterol loaded solid lipid nanoparticles (SLN) against complete Fruend adjuvant (CFA)-induced arthritis via dual pathway. Double emulsion solvent displacement method was used for the preparation of β-sitosterol solid lipid nanoparticles (SLN). CFA was used to induce arthritis and rats were divided into different groups for 28 days. Biochemical, anti-inflammatory, pro-inflammatory cytokines and inflammatory mediator were estimated, respectively. Receptor activator of nuclear factor kappa-B ligand (RANKL), signal transducer and activator of transcription-3 (STAT3) nuclear factor erythroid 2-related factor 2 (Nrf), Heme Oxygenase-1(HO-1) and Nuclear factor-κB (NF-κB) expression were estimated. β-sitosterol-SLN significantly ( < .001) reduced the paw edema, arthritic index and increased the body weight. β-sitosterol-SLN increased the redox status of synovium {reduce the malonaldehyde (MDA) and increase superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT)} level and reduced the cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2, interleukin-6, interleukin-16, interleukin-17 and increased level of interleukin-10, Transforming growth factor beta (TGF-β). β-sitosterol-SLN significantly ( < .001) reduced the level of cyclooxygenase-2 (COX-2), prostaglandin E (PGE), vascular Endothelial Growth Factor (VEGF) and NF-κB. β-sitosterol-SLN significantly increased the expression of HO-1,Nrf and decreased the expression of NF-κB, RANKL, STAT3. In conclusion, β-sitosterol SLN showed the antiarthritic effect via suppression of NF-kB and activation of HO-1/Nrf-2 pathway.
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http://dx.doi.org/10.1080/10717544.2020.1818883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534215PMC
December 2020

Nomograms for predicting overall survival and cancer-specific survival of chondroblastic osteosarcoma patients.

J Surg Oncol 2020 Dec 29;122(8):1676-1684. Epub 2020 Aug 29.

Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: The establishment of precise and personalized prediction systems for chondroblastic osteosarcoma patients is important for guiding the treatment.

Methods: The univariate logrank test and multivariate Cox regression analysis were performed to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Nomograms were constructed to estimate the OS and CSS based on these factors. Internal and external validation was performed. The predictive power of the nomograms was determined by C-index and calibration plots.

Results: A total of 401 chondroblastic osteosarcoma cases were identified. Univariate and multivariate analysis revealed that age at diagnosis, histological grade, tumor size, Surveillance, Epidemiology, and End Results stage, and surgical resection were independent prognostic factors for OS and CSS. The five factors were incorporated to construct the nomograms for estimating the 3- and 5-year OS and CSS. The C-index values for the internal validation of the OS and CSS nomogram were 0.732 and 0.746, respectively, and for the external validation were 0.780 and 0.808, respectively. The calibration curves revealed that the predicted OS and CSS could well match the actual survival rate.

Conclusions: The nomograms for predicting 3- and 5-year OS and CSS were constructed and were proved to be accurate and reliable by the internal and external validation.
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http://dx.doi.org/10.1002/jso.26185DOI Listing
December 2020

MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury.

Life Sci 2020 Aug 14;254:117796. Epub 2020 May 14.

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China. Electronic address:

Aims: To explore the possible mechanism that microRNA-223 regulates the spinal cord injury as well as the posttranscriptional control of genes after spinal injury.

Materials And Methods: Rats contusion spinal cord injury model and microglia model were established and examined by pathological test and the inflammatory cytokines levels were evaluated by RT-PCR. Then microRNA-223 was overexpressed in spinal cord to see the impact on rats with spinal cord injury. The overexpression of microRNA-223 in microglia stimulated by LPS was used to assess the inflammation. Then bioinformatic method combined with luciferase reporter genes were used to detect the target gene of microRNA-223. Then NLRP3, one of the target genes of microRNA-223 were regulated to see the impact on microglia as well as spinal injury rats.

Key Findings: It showed that microRNA-223 increased after acute spinal injury. However, the suppression of microRNA-223 aggravated the spinal injury as well as the inflammation while the over-expression of microRNA-223 alleviated the spinal injury to some extent, decreased the inflammation and improved nervous system function. In vitro, it was found that the over-expression of microRNA-223 in microglia suppressed inflammation induced by LPS and vice versa. NLRP3 was found the target of microRNA-223. The up-regulation of NLRP3 could diminish the effects of microRNA-223 and aggravated inflammation in microglia.

Significance: The over-expression of microRNA-223 alleviated the inflammation and improved neuron function. NLRP3 was the downstream target of microRNA-223, the overexpression of which led to severe inflammation in microglia.
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http://dx.doi.org/10.1016/j.lfs.2020.117796DOI Listing
August 2020

Transplantation of ACE2 Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

Aging Dis 2020 Apr 9;11(2):216-228. Epub 2020 Mar 9.

9The Executive Committee on Anti-aging and Disease Prevention in the framework of Science and Technology, Pharmacology and Medicine Themes under an Interactive Atlas along the Silk Roads, UNESCO, Paris, France.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2 and TMPRSS2 which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
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http://dx.doi.org/10.14336/AD.2020.0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069465PMC
April 2020

Transplantation of sh-miR-199a-5p-Modified Olfactory Ensheathing Cells Promotes the Functional Recovery in Rats with Contusive Spinal Cord Injury.

Cell Transplant 2020 Jan-Dec;29:963689720916173

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

MicroRNAs (miRNAs) function as gene expression switches, and participate in diverse pathophysiological processes of spinal cord injury (SCI). Olfactory ensheathing cells (OECs) can alleviate pathological injury and facilitate functional recovery after SCI. However, the mechanisms by which OECs restore function are not well understood. This study aims to determine whether silencing miR-199a-5p would enhance the beneficial effects of the OECs. In this study, we measured miR-199a-5p levels in rat spinal cords with and without injury, with and without OEC transplants. Then, we transfected OECs with the sh-miR-199a-5p lentiviral vector to reduce miR-199a-5p expression and determined the effects of these OECs in SCI rats by Basso-Beattie-Bresnahan (BBB) locomotor scores, diffusion tensor imaging (DTI), and histological methods. We used western blotting to measure protein levels of Slit1, Robo2, and srGAP2. Finally, we used the dual-luciferase reporter assay to assess the relationship between miR-199-5p and Slit1, Robo2, and srGAP2 expression. We found that SCI significantly increased miR-199a-5p levels ( < 0.05), and OEC transplants significantly reduced miR-199a-5p expression ( < 0.05). Knockdown of miR-199a-5p in OECs had a better therapeutic effect on SCI rats, indicated by higher BBB scores and fractional anisotropy values on DTI, as well as histological findings. Reducing miR-199a-5p levels in transplanted OECs markedly increased spinal cord protein levels of Slit1, Robo2, and srGAP2. Our results demonstrated that transplantation of sh-miR-199a-5p-modified OECs promoted functional recovery in SCI rats, suggesting that miR-199a-5p knockdown was more beneficial to the therapeutic effects of OEC transplants. These findings provided new insights into miRNAs-mediated therapeutic mechanisms of OECs, which helps us to develop therapeutic strategies based on miRNAs and optimize cell therapy for SCI.
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http://dx.doi.org/10.1177/0963689720916173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586279PMC
June 2021

A survey of 434 clinical trials about coronavirus disease 2019 in China.

J Med Virol 2020 10 27;92(10):1715-1717. Epub 2020 Mar 27.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

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http://dx.doi.org/10.1002/jmv.25779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228410PMC
October 2020

Interface Fixation Using Absorbable Screws versus Plate Fixation in Anterior Cervical Corpectomy and Fusion for Two-Level Cervical Spondylotic Myelopathy.

Med Sci Monit 2020 Mar 20;26:e921507. Epub 2020 Mar 20.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henen, China (mainland).

BACKGROUND We compared the clinical and radiographic outcomes between interface fixation using absorbable screws and plate fixation in anterior cervical corpectomy and fusion (ACCF) to evaluate the effectiveness of these 2 fixation methods for the treatment of 2-level cervical spondylotic myelopathy (CSM). MATERIAL AND METHODS From January 2014 to December 2016, a total of 220 patients who received 2-level ACCF were retrospectively collected. Among them, 108 patients were treated with interface fixation using absorbable screws (Group A) and 112 patients underwent plate fixation (Group B). Japanese Orthopedic Association (JOA) score and Neck Disability Index (NDI) score were employed to compare the clinical improvement. Operative time, blood loss, surgical cost, cervical lordosis, complications, and fusion rate were also evaluated. RESULTS The average follow-up time were 35.2±4.5 months in Group A and 35.9±3.9 months in Group B. There was no difference in operative time and blood loss for both groups. The JOA scores and NDI scores were similar in each follow-up (p>0.05 in all). Group A cost an average of 30% less than Group B for the operation. Both groups achieved 100% in the fusion rate with the same conditions in cervical lordosis. Group A (5/108) had a significantly lower complication rate than Group B (17/112) (p<0.05). CONCLUSIONS ACCF with interface fixation using absorbable screws achieved similar clinical outcomes compared to ACCF with plate fixation for 2-level CSM. Moreover, the interface fixation using absorbable screws presented far fewer complications and cost less for the operation.
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http://dx.doi.org/10.12659/MSM.921507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106970PMC
March 2020

Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2.

Nat Neurosci 2020 03;23(3):337-350

Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. Our data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.
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http://dx.doi.org/10.1038/s41593-020-0597-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412870PMC
March 2020

Methane attenuates lung ischemia-reperfusion injury via regulating PI3K-AKT-NFκB signaling pathway.

J Recept Signal Transduct Res 2020 Jun 21;40(3):209-217. Epub 2020 Feb 21.

Department of Hepatobiliary Surgery, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

This study aims to investigate the protective effects and possible mechanism of methane-rich saline (MS) on lung ischemia-reperfusion injury (LIRI) in rats. MS (2 ml/kg and 20 ml/kg) was injected intraperitoneally in rats after LIRI. Lung injury was assayed by Hematoxylin-eosin (HE) staining and wet-to-dry weight (W/D). The cells in the bronchoalveolar lavage fluid (BALF) and blood were counted. Oxidative stress was examined by the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were determined by ELISA. Lung tissue apoptosis was detected by TUNEL staining and western blotting of Bcl-2, Bax, and caspase-3. The expressions of IкBα, p38, PI3K, AKT, and NF-κB were analyzed with Western blotting. MS effectively decreased the lung W/D ratio as well as the lung pathological damage and reduced the localized infiltration of inflammatory cells. Methane suppressed the expression of the PI3K-AKT-NFκB signaling pathway during the lung IR injury, which inhibited the activation of NF-kB and decreased the level of inflammatory cytokines, such as TNF-α, IL-1β, and IL-10. Moreover, we found that MS treatment relieved reactive oxygen species (ROS) damage by downregulating MDA and upregulating SOD. MS treatment also regulated apoptosis-related proteins, such as Bcl-2, Bax, and caspase-3. MS could repair LIRI and reduce the release of oxidative stress, inflammatory cytokines, and cell apoptosis via the PI3K-AKT-NFκB signaling pathway, which may provide a novel and promising strategy for the treatment of LIRI.
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http://dx.doi.org/10.1080/10799893.2020.1727925DOI Listing
June 2020

Biomechanical Comparison of 1-Level Corpectomy and 2-Level Discectomy for Cervical Spondylotic Myelopathy: A Finite Element Analysis.

Med Sci Monit 2020 Feb 5;26:e919270. Epub 2020 Feb 5.

State Key Laboratory for Manufacturing Systems Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND Anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) are effective treatments for cervical spondylotic myelopathy (CSM), but it is unclear which is better. In this study, we compared the biomechanical properties of 2-level ACDF and 1-level ACCF. MATERIAL AND METHODS An intact C3-C7 cervical spine model was developed and validated, then ACDF and ACCF simulation models were developed. We imposed 1.0 Nm moments and displacement-controlled loading on the C3 superior endplate. The range of motions (ROMs) of surgical and adjacent segments and von Mises stresses on endplates, fixation systems, bone-screw interfaces, and bone grafts were recorded. RESULTS ACDF and ACCF significantly reduced the surgical segmental ROMs to the same extent. ACCF induced much lower stress peaks in the fixation system and bone-screw interfaces and higher stress peaks on the bone graft. ACDF induced much lower stress peaks on the C4 inferior endplate and equivalent stress on the C6 superior endplate. There was no difference in the ROMs of surgical and adjacent segments and the intradiscal stress of adjacent levels between ACDF and ACCF. CONCLUSIONS Both ACDF and ACCF can provide satisfactory spinal stability. ACDF may be beneficial for subsidence resistance due to the lower stress peaks on the endplate. The ACCF may perform better in long-term stability and bone fusion owing to the lower stress peaks in the fixation system and bone-screw interfaces, and higher stress peaks in the bone graft.
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http://dx.doi.org/10.12659/MSM.919270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020763PMC
February 2020

Prognostic Factors and Treatment Options for Patients with High-Grade Chondrosarcoma.

Med Sci Monit 2019 Nov 25;25:8952-8967. Epub 2019 Nov 25.

Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND The goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma. MATERIAL AND METHODS Surveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis. RESULTS A total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens. CONCLUSIONS Our study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients' outcome.
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http://dx.doi.org/10.12659/MSM.917959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894367PMC
November 2019

Corrigendum to "Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing".

Biomed Res Int 2019;2019:3132626. Epub 2019 Sep 26.

Department of Orthopaedic Surgery, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, China.

[This corrects the article DOI: 10.1155/2016/3684875.].
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http://dx.doi.org/10.1155/2019/3132626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791215PMC
September 2019

Notch signaling regulates osteosarcoma proliferation and migration through Erk phosphorylation.

Tissue Cell 2019 Aug 2;59:51-61. Epub 2019 Jul 2.

The Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, PR China. Electronic address:

We used a murine spontaneous osteosarcoma cell line with high metastatic potential, the K7M2 cell line to study the role of Notch signaling in the biological manifestations of osteosarcoma, to understand its underlying mechanism in the regulation of cell proliferation and migration, and to improve patient prognosis in cases of osteosarcoma through the discovery of novel therapeutic targets, First, Notch expression in K7M2 was determined by immunostaining, and the γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) was used to inhibit proteolytic cleavage of the Notch intracellular domain (NICD), resulting in the inhibition of Notch activation. By using the Sulforhodamine B assay, colony-forming units assay, Brdu and Ki67 staining, and flow cytometry assays of apoptosis and cell cycle stage, DAPT was found to inhibit K7M2 proliferation in a dose-dependent manner. By using wound healing and transwell migration assays, DAPT was found to inhibit K7M2 migration in a dose-dependent manner as well. By using a combination of micro-Raman spectroscopy and K-means clustering analysis, we found that DAPT inhibit a variety of important cell metabolism-related components in most K7M2 cell structures. Then, DAPT was found to inhibit Notch1ICD expression in a concentration-dependent manner, and this expression was directly correlated with Phospho-Erk1/2 (p-Erk) by using Western blotting. To confirm this finding, we used the Notch signaling ligand Jagged1 to activate the Notch signaling pathway, which in turn up-regulated p-Erk, resulting in increased proliferation and migration of K7M2. Using the Erk pathway inhibitor U0126, we showed that p-Erk was downregulated and the proliferation and migration of K7M2 decreased along with it. Finally, we constructed a K7M2 mouse para-tibial tumor model and lung metastatic model. We found DAPT inhibits p-Erk in vivo, effectively controls tumor growth, reduces angiogenesis, reduces metastasis to the lungs, and improves overall survival. In summary, Notch signaling plays an oncogene role and promotes metastasis in osteosarcoma through p-Erk. DAPT effectively inhibits osteosarcoma proliferation and metastasis in vivo and in vitro by inhibiting Erk phosphorylation. Therefore, the inhibition of Notch activation resulted the down-regulation of phosphorylation of Erk pathway can be used as potential therapeutic targets in clinical treatment to improve osteosarcoma prognosis.
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http://dx.doi.org/10.1016/j.tice.2019.07.002DOI Listing
August 2019

miR-99b-3p is induced by vitamin D3 and contributes to its antiproliferative effects in gastric cancer cells by targeting HoxD3.

Biol Chem 2019 Jul 9. Epub 2019 Jul 9.

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Health Science Center, No. 76, Yanta West Road, Xi'an, Shaanxi 710061, China.

Vitamin D3 is known to have anticancer actions by affecting tumorigenesis including the cell cycle and cell apoptosis in gastric cancer (GC) cells; the genes including microRNAs (miRNAs) regulated by vitamin D3 signaling remain discovered. miR-99b-3p, the tumor suppressor gene, is not only decreased in GC tissues, but is also induced by vitamin D3 through the vitamin D receptor (VDR) binding on the promoter domain of miR-99b. Further study indicates that miR-99b-3p inhibits cell viability and induces cell arrest in the S-phase in GC cells, the direct target gene of miR-99b-3p is verified to be HoxD3, which is also overexpressed in GC cell lines. Overall, our results show that miR-99b-3p mediates the antiproliferative of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.
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http://dx.doi.org/10.1515/hsz-2019-0102DOI Listing
July 2019

Clinical comparison between a percutaneous hydraulic pressure delivery system and balloon tamp system using high-viscosity cement for the treatment of osteoporotic vertebral compression fractures.

Clinics (Sao Paulo) 2019 30;74:e741. Epub 2019 May 30.

The Department of Orthopedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, P. R. of China.

Objectives: Osteoporotic vertebral compression fractures (OVCFs) affect the elderly population, especially postmenopausal women. Percutaneous kyphoplasty is designed to treat painful vertebral compression fractures for which conservative therapy has been unsuccessful. High-viscosity cement can be injected by either a hydraulic pressure delivery system (HPDS) or a balloon tamp system (BTS). Therefore, the purpose of this study was to compare the safety and clinical outcomes of these two systems.

Methods: A random, multicenter, prospective study was performed. Clinical and radiological assessments were carried out, including assessments of general surgery information, visual analog scale, quality of life, cement leakage, and height and angle restoration.

Results: Using either the HPDS or BTS to inject high-viscosity cement effectively relieved pain and improved the patients' quality of life immediately, and these effects lasted at least two years. The HPDS using high-viscosity cement reduced cost, surgery time, and radiation exposure and showed similar clinical results to those of the BTS. In addition, the leakage rate and the incidence of adjacent vertebral fractures after the HPDS treatment were reduced compared with those after treatment using the classic vertebroplasty devices. However, the BTS had better height and angle restoration abilities.

Conclusions: The percutaneous HPDS with high-viscosity cement has similar clinical outcomes to those of traditional procedures in the treatment of vertebral fractures in the elderly. The HPDS with high-viscosity cement is better than the BTS in the treatment of mild and moderate OVCFs and could be an alternative method for the treatment of severe OVCFs.
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http://dx.doi.org/10.6061/clinics/2019/e741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530436PMC
December 2019

Time and Frequency Characteristics of Cavitation Activity Enhanced by Flowing Phase-Shift Nanodroplets and Lipid-Shelled Microbubbles During Focused Ultrasound Exposures.

Ultrasound Med Biol 2019 08 29;45(8):2118-2132. Epub 2019 May 29.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China. Electronic address:

This study investigated and compared the time and frequency characteristics of cavitation activity between phase-shift nanodroplets (NDs) and lipid-shelled microbubbles (MBs) exposed to focused ultrasound (FUS) under physiologically relevant flow conditions. Root-mean-square (RMS) of broadband noise, spectrograms of the passive cavitation detection signals and inertial cavitation doses (ICDs) were calculated during FUS at varying mean flow velocities and two different peak-rarefactional pressures. At a lower pressure of 0.94 MPa, the mean values of the RMS amplitudes versus time for the NDs showed an upward trend but slowed down as the mean flow velocity increased. For flowing NDs, the rate of growth in RMS amplitudes within 2-5 MHz decreased more obviously than those within 5-8 MHz. At a higher pressure of 1.07 MPa, the increase in RMS amplitudes was accelerated as the mean flow velocity increased from 0 to 10 cm/s and slowed down as the mean flow velocity reached 15 cm/s. The general downward trends of RMS amplitudes for the MBs were retarded as the mean flow velocity increased at both acoustic pressures of 0.94 MPa and 1.07 MPa. At 0.94 MPa, the mean ICD value for the NDs decreased from 57 to 36 as the mean flow velocity increased from 0 to 20 cm/s. At 1.07 MPa, the mean ICD value initially increased from 45 to 57 as the mean flow velocity increased from 0 to 10 cm/s and subsequently decreased to 43 as the mean flow velocity reached 20 cm/s. For the MBs, the mean ICD value increased with increasing mean flow velocity at both acoustic pressures. These results could aid in future investigations of cavitation-enhanced FUS with the flowing phase-shift NDs and encapsulated, gas-filled MBs for various applications.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2019.04.024DOI Listing
August 2019

Effects of New Cage Profiles on the Improvement in Biomechanical Performance of Multilevel Anterior Cervical Corpectomy and Fusion: A Finite Element Analysis.

World Neurosurg 2019 Sep 29;129:e87-e96. Epub 2019 May 29.

Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address:

Background: For multilevel cervical fusion, anterior corpectomy and fusion (ACCF) induces more implant-related complications than anterior diskectomy and fusion (ACDF), which implies that the biomechanical stability of ACCF may be insufficient. The aim of this study was to assess whether the optimization of the cage profiles could improve the biomechanical performance of multilevel ACCF.

Methods: Three finite element models were constructed and compared, including 3-level ACDF, 2-level ACCF using a conventional cage for reconstruction, and 2-level ACCF using a new cage for reconstruction. The ends of the new cage possessed additional end rings and emulated the end plate geometries. The ranges of motion (ROMs) of the surgical segments and the stress peaks in the end plate, fixation system, and screw-bone interface were compared.

Results: Compared with preoperative status, ACDF and ACCF reduced the segmental ROMs by 96.1%-98.2%. The end plate stress peaks were the highest in ACCF using the conventional cage (10.1-18.6 MPa), followed by ACCF using the new cage (7.7-14.3 MPa) and ACDF (5.3-9.1 MPa). ACDF induced the highest stress peaks in the fixation system and screw-bone interface (32.5-39.3 MPa and 12.1-12.7 MPa, respectively), followed by ACCF using the conventional cage (20.4-31.7 MPa and 10.3-13.6 MPa, respectively) and ACCF using the new cage (18.6-25.7 MPa and 9.7-12.6 MPa, respectively).

Conclusions: The application of the new cage decreased the risks of cage subsidence and instrument-related complications in multilevel ACCF. Under the condition where cage subsidence was prevented, ACCF was superior to ACDF in terms of construct stability and avoiding instrument-related complications.
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http://dx.doi.org/10.1016/j.wneu.2019.05.037DOI Listing
September 2019

[Effects of a new anatomical adaptive titanium mesh cage on supportive load at the cervical endplate: a morphological and biomechanical study].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Apr;39(4):409-414

Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

Objective: To assess the geometrical matching of a new anatomical adaptive titanium mesh cage (AA-TMC) with the endplate and its effect on cervical segmental alignment reconstruction in single- and two-level anterior cervical corpectomy and fusion (ACCF) and compare the compressive load at the endplate between the AA-TMC and the conventional titanium mesh cage (TMC).

Methods: Twelve cervical cadaveric specimens were used to perform single- and two-level ACCF. The interbody angle (IBA), interbody height (IBH) and the interval between the AA-TMC and the endplate were evaluated by comparison of the pre- and postoperative X-ray images. The maximum load at the endplate was compared between the AA-TMC and TMC based on American Society for Testing and Materials (ASTM) F2267 standard.

Results: No significant differences were found between the preoperative and postoperative IBA and IBH in either single-level ACCF (11.62°±2.67° 12.13°±0.69° and 23.90±2.18 mm 24.23±1.13 mm, respectively; > 0.05) or two-level ACCF (15.63°±5.06° 16.16°±1.05°and 42.93±3.51 mm 43.04±1.70 mm, respectively; > 0.05). The mean interval between the AA-TMC and the endplate was 0.37 ± 0.3 mm. Compared to the conventional TMC, the use of AA-TMC significantly increased the maximum load at the endplate in both single-level ACCF (719.7±5.5 N 875.8±5.2 N, < 0.05) and two-level ACCF (634.3±5.9 N 873±6.1 N, < 0.05).

Conclusions: The use of AA-TMC in single-level and two-level ACCF can significantly increase the maximum load at the endplate to lower the possibility of implant subsidence and allows effective reconstruction of the cervical alignment.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.04.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743989PMC
April 2019

Quantitative Analysis of SSEA3+ Cells from Human Umbilical Cord after Magnetic Sorting.

Cell Transplant 2019 07 18;28(7):907-923. Epub 2019 Apr 18.

2 W.M. Keck Center for Collaborative Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey, USA.

Multilineage-differentiating stress-enduring (Muse) cells are a population of pluripotent stage-specific embryonic antigen 3 (SSEA3)+ mesenchymal stem cells first described by Mari Dezawa in 2010. Although some investigators have reported SSEA3+ mesenchymal cells in umbilical cord tissues, none have quantitatively compared SSEA3+ cells isolated from Wharton's jelly (WJ) and the cord lining (CL) of human umbilical cords (HUCs). We separated WJ and the CL from HUCs, cultured mesenchymal stromal cells (MSCs) isolated from these two tissues with collagenase, and quantified the percentage of SSEA3+ cells over three passages. The first passage had 5.0% ± 4.3% and 5.3% ± 5.1% SSEA3+ cells from WJ and the CL, respectively, but the percentage of SSEA3+ cells decreased significantly ( < 0.05) between P0 and P2 in the CL group and between P0 and P1 in the WJ group. Magnetic-activated cell sorting (MACS) markedly enriched SSEA3+ cells to 91.4% ± 3.2%. Upon culture of the sorted population, we found that the SSEA3+ percentage ranged from 62.5% to 76.0% in P2-P5 and then declined to 42.0%-54.7% between P6 and P9. At P10, the cultures contained 37.4% SSEA3+ cells. After P10, we resorted the cells and achieved 89.4% SSEA3+ cells in culture. The procedure for MACS-based enrichment of SSEA3+ cells, followed by expansion in culture and a re-enrichment step, allows the isolation of many millions of SSEA3+ cells in relatively pure culture. When cultured, the sorted SSEA3+ cells differentiated into embryoid spheres and survived 4 weeks after transplant into a contused Sprague-Dawley rat spinal cord. The transplanted SSEA3+ cells migrated into the injury area from four injection points around the contusion site and did not produce any tumors. The umbilical cord is an excellent source of fetal Muse cells, and our method allows the practical and efficient isolation and expansion of relatively pure populations of SSEA3+ Muse cells that can be matched by human leukocyte antigen for transplantation in human trials.
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http://dx.doi.org/10.1177/0963689719844260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719495PMC
July 2019