Publications by authors named "Xiaobing Yu"

71 Publications

Molecular Genetics and Complex Inheritance of Congenital Heart Disease.

Genes (Basel) 2021 Jun 30;12(7). Epub 2021 Jun 30.

Department of Genetics, School of Medicine, Washington University, St. Louis, MO 63110, USA.

Congenital heart disease (CHD) is the most common congenital malformation and the leading cause of mortality therein. Genetic etiologies contribute to an estimated 90% of CHD cases, but so far, a molecular diagnosis remains unsolved in up to 55% of patients. Copy number variations and aneuploidy account for ~23% of cases overall, and high-throughput genomic technologies have revealed additional types of genetic variation in CHD. The first CHD risk genotypes identified through high-throughput sequencing were de novo mutations, many of which occur in chromatin modifying genes. Murine models of cardiogenesis further support the damaging nature of chromatin modifying CHD mutations. Transmitted mutations have also been identified through sequencing of population scale CHD cohorts, and many transmitted mutations are enriched in cilia genes and Notch or VEGF pathway genes. While we have come a long way in identifying the causes of CHD, more work is required to end the diagnostic odyssey for all CHD families. Complex genetic explanations of CHD are emerging but will require increasingly sophisticated analysis strategies applied to very large CHD cohorts before they can come to fruition in providing molecular diagnoses to genetically unsolved patients. In this review, we discuss the genetic architecture of CHD and biological pathways involved in its pathogenesis.
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http://dx.doi.org/10.3390/genes12071020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307500PMC
June 2021

CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues.

Blood 2021 06 3. Epub 2021 Jun 3.

Karlsruhe Institute of Technology, Institute of Biological and Chemical Systems - Functional Molecular Systems, Karlsruhe, Germany.

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients, ineligible for intensive induction chemotherapy. Complete remission rates with venetoclax-based therapies are, however, hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. MRD is due to leukemic stem cells retained in bone marrow protective environments; activation of the CXCL12/CXCR4 pathway was shown to be relevant to this process. An important role is also played by cell adhesion molecules such as CD44, which has been shown to be crucial for AML development. Here we show that CD44 is involved in CXCL12 promotion of resistance to venetoclax-induced apoptosis in human AML cell lines and AML patient samples which could be abrogated by CD44 knockdown, knockout or blocking with an anti-CD44 antibody. Split-Venus biomolecular fluorescence complementation showed that CD44 and CXCR4 physically associate at the cell membrane upon CXCL12 induction. In the venetoclax-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic-stem-cell core transcription factors (ESC-TFs: Sox2, Oct4, Nanog), abrogated by CD44 knockdown. This ESC-TF-expressing subpopulation which could be selected by venetoclax treatment, exhibited a basally-enhanced resistance to apoptosis, and expressed higher levels of CD44. Finally, we developed a novel AML xenograft model in zebrafish, showing that CD44 knockout sensitizes OCI-AML3 cells to venetoclax treatment in vivo. Our study shows that CD44 is a potential molecular target to sensitize AML cells to venetoclax-based therapies.
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http://dx.doi.org/10.1182/blood.2020006343DOI Listing
June 2021

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats.

Stem Cell Res Ther 2021 06 10;12(1):334. Epub 2021 Jun 10.

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian, 116001, Liaoning Province, China.

Background: How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances.

Methods: We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, RESULTS: In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI).

Conclusions: In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.
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http://dx.doi.org/10.1186/s13287-021-02401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193895PMC
June 2021

Changes in Macular Microvascular Structure in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Antivascular Endothelial Growth Factor for One Year.

J Ophthalmol 2021 17;2021:6645452. Epub 2021 May 17.

Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Purpose: To observe the changes in macular microvascular structure and the correlation between anatomy and visual function in patients with macular edema secondary to branch retinal vein occlusion (BRVO) treated with antivascular endothelial growth factor for one year.

Methods: This prospective study enrolled 39 patients (one eye per patient) who received intravitreal injections of ranibizumab for macular edema secondary to BRVO. All patients received a minimum of 3 initial monthly ranibizumab injections and criteria-driven pro re nata (PRN) dosing thereafter for visual acuity (VA) and central retinal thickness (CRT) stabilization. The follow-up period of this study was one year. The vascular density (VD) of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter, the VD within a 300 m wide ring surrounding the FAZ (FD-300), and the acircularity index (AI) were measured automatically by optical coherence tomography angiography (OCTA) at baseline, month 6, and month 12.

Results: Compared with those before treatment, the VD of the SCP significantly decreased 6 months after treatment ( < 0.05), while the area and perimeter of the FAZ increased significantly ( < 0.01). After 12 months of treatment, the area and perimeter of the FAZ increased significantly ( < 0.01). There was no significant difference in any parameters between 12 months and 6 months after treatment ( > 0.05). The change in BCVA was negatively correlated with the VD of the SCP at 12 months (=0.0447,  = -0.3233). There was a relationship between the DBP and AI, and CRT was related to VD of DCP at baseline (=0.028,  0.0209;  = 0.383, -0.384). The PERIM and AI at 12 months were significantly associated with the recurrence of macular edema, and the changes in vascular density in the SCP and PERIM were significantly associated with the number of injections within 12 months ( < 0.05).

Conclusions: One year after ranibizumab treatment, the area and perimeter of the FAZ were enlarged, while the VD of the SCP and DCP remained stable, which indicated that ranibizumab treatment did not improve macular blood supply and macular ischemia in BRVO patients.
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http://dx.doi.org/10.1155/2021/6645452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149245PMC
May 2021

Transcriptome landscape of the late-stage alcohol-induced osteonecrosis of the human femoral head.

Bone 2021 09 18;150:116012. Epub 2021 May 18.

Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China; Laboratory of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China; National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China. Electronic address:

Osteonecrosis resulting from heavy ethanol consumption is one of the major causes of nontraumatic osteonecrosis of the femoral head (ONFH). The underlying pathological and molecular mechanisms remain elusive. In this study, we performed deep RNA sequencing from femoral heads of patients diagnosed with late-stage alcohol-induced ONFH (AIONFH), other types of ONFH and traumatic injury (bone fracture). Genome-wide gene expression analyses identified 690 differentially expressed mRNAs in AIONFH. Gene annotation and pathway analyses revealed significant dysregulated genes involved in hemostasis, angiogenesis and bone remodeling processes from the late-stage AIONFH. Notably, ADH1B, which codes for one of the major alcohol dehydrogenases, is significantly upregulated in AIONFH samples. Further, we found that the ADH1B protein was primarily expressed in smooth muscle cells of the blood vessels, stromal cells and adipocytes of the femoral heads of AIONFH patients; but was absent in other ONFH samples. Our analyses also revealed unique long non-coding RNA (lncRNA) expression profiles and identified novel lncRNAs in AIONFH. In addition, we observed a close co-expression correlation between lncRNAs and mRNAs in AIONFH suggesting that cis-gene regulation represents a major mechanism of action of human femoral lncRNAs. Further, the expression signature of lncRNAs, but not mRNAs, distinguishes AIONFH from other types of ONFH. Taken together, our studies uncovered novel molecular signatures associated with late-stage AIONFH in which the dysregulation of several key signaling pathways within the femoral head may be involved in AIONFH. Subsequently, lncRNAs may serve as potential biomarkers for diagnosis and therapeutic treatment of AIONFH. Further studies are needed to confirm that ADH1B is specifically upregulated in AIONFH and not generally upregulated in patients who consume alcohol excessively.
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http://dx.doi.org/10.1016/j.bone.2021.116012DOI Listing
September 2021

Early neurovascular changes in the retina in preclinical diabetic retinopathy and its relation with blood glucose.

BMC Ophthalmol 2021 May 17;21(1):220. Epub 2021 May 17.

Department of Endocrinology, Beijing Hospital, Nations Center of Gerontology, Beijing, China.

Background: To investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose.

Methods: In this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups.

Results: The parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p < 0.05) in the diabetic group than in the normal group. The diabetic group showed a higher acircularity index than the normal group. The normal group had the highest vessel density and the lowest acircularity index, followed by the no-diabetic retinopathy group and the mild non-proliferative retinopathy group, (p < 0.001). Foveal vascular density and parafoveal vessel density decreased with an increase in HbA1c. There was a negative correlation between parafoveal vessel density in the deep retinal vascular layer and fasting blood glucose (p < 0.01). The temporal retinal nerve fiber layer thickness decreased across the HbA1c level groups, and was positively correlated with the parafoveal vessel density in the superficial retinal vascular layer (p < 0.05).

Conclusions: This study shows that retinal microvasculopathy and neuropathy can be present in the absence of retinopathy. The vessel density of the deep retinal vascular layer was negatively correlated with fasting blood glucose, and the temporal retinal nerve fiber layer thickness was positively correlated with the vessel density of the superficial retinal vascular layer. These indicators are helpful for endocrinologists and ophthalmologists in detecting early diabetic retinal pathological lesions.
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http://dx.doi.org/10.1186/s12886-021-01975-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130389PMC
May 2021

Contribution of colony-stimulating factor 1 to neuropathic pain.

Pain Rep 2021 9;6(1):e883. Epub 2021 Mar 9.

Deaprtments of Anesthesia and Perioperative Care and.

Molecular and cellular interactions among spinal dorsal horn neurons and microglia, the resident macrophages of the central nervous system, contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. Emerging evidence also demonstrates that reciprocal interactions between macrophages and nociceptive sensory neurons in the dorsal root ganglion contribute to the initiation and persistence of nerve injury-induced mechanical hypersensitivity (allodynia). We previously reported that sensory neuron-derived colony-stimulating factor 1 (CSF1), by engaging the CSF1 receptor (CSF1R) that is expressed by both microglia and macrophages, triggers the nerve injury-induced expansion of both resident microglia in the spinal cord and macrophages in the dorsal root ganglion and induces their respective contributions to the neuropathic pain phenotype. Here, we review recent research and discuss unanswered questions regarding CSF1/CSF1R-mediated microglial and macrophage signaling in the generation of neuropathic pain.
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http://dx.doi.org/10.1097/PR9.0000000000000883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108585PMC
March 2021

Clinical Benefit of Rehabilitation Training in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Spine (Phila Pa 1976) 2021 Mar;46(6):E398-E410

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.

Study Design: A systematic review and meta-analysis.

Objective: This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury.

Summary Of Background Data: Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial.

Methods: Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software.

Results: Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls.

Conclusion: Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.Level of Evidence: 1.
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http://dx.doi.org/10.1097/BRS.0000000000003789DOI Listing
March 2021

Cardiopulmonary and Neurologic Dysfunctions in Fibrodysplasia Ossificans Progressiva.

Biomedicines 2021 Feb 5;9(2). Epub 2021 Feb 5.

Department of Medicine, Division of Endocrinology and Metabolism, the Institute for Human Genetics, and the Program in Craniofacial Biology, University of California, San Francisco, CA 94143, USA.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Emerging evidence reveals important cardiopulmonary and neurologic dysfunctions in FOP including thoracic insufficiency syndrome, pulmonary hypertension, conduction abnormalities, neuropathic pain, and demyelination of the central nervous system (CNS). Here, we review the recent research and discuss unanswered questions regarding the cardiopulmonary and neurologic phenotypes in FOP.
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http://dx.doi.org/10.3390/biomedicines9020155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915901PMC
February 2021

Primary multiple angiosarcoma of vertebra: A case report.

Medicine (Baltimore) 2020 Dec;99(50):e23587

Department of Orthopaedics, Zhongshan Hospital of Dalian University, Dalian, 116001, China.

Rationale: Angiosarcoma is a rare malignant tumors. The objective of this study is to report a patient who suffered from a progressive low back pain and left lower extremities radiation pain for about 8 months, After diagnoses, this was identified as an extremely rare case of primary multiple angiosarcoma of vertebra.

Patient Concerns: A 54-year-old man with a history of 2-year hypertension and 8-year diabetes, both of which were well controlled by drug management. Lately, he suffered from a progressive low back pain and left lower extremities radiation pain for about 8 months.

Diagnoses: Magnetic resonance imaging of lumbar showed a clear pathological fracture and primary multiple angiosarcoma of all vertebra. Postoperative pathology and High-throughput sequencing confirmed the diagnosis of primary multiple angiosarcoma of vertebra.

Interventions: The patient underwent minimally invasive pedicle screw fixation combined with bone cement augmentation for the purpose of stabilizing the damaged vertebrae. Following operation, he received both radiotherapy and chemotherapy for a period of time.

Outcomes: The operation has achieved positive results in relieving pain and stabilizing the spine. No wound problem or operative complications occurred after operation. The patient reported an obvious remission of low back pain and was only capable to perform restricted physiological activities. A long-term palliative radiotherapy and chemotherapy were performed after operation. Unfortunately, the patient died 18 months later.

Conclusion: This article emphasizes primary multiple angiosarcoma of vertebra. Despite being rare, it should be part of the differential when the patient manifested back pain and radiculopathy. We recommended the minimally invasive pedicle screw fixation for angiosarcoma of vertebra. Osteoplasty by bone cement augmentation was also an ideal choice for surgical treatment. It also advocates the use of specific targeted radiotherapy drugs based on gene analysis of tumors.
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http://dx.doi.org/10.1097/MD.0000000000023587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738032PMC
December 2020

Maxillary Nerve-Mediated Postseptoplasty Nasal Allodynia: A Case Report.

A A Pract 2020 Nov;14(13):e01356

From the Department of Anesthesia and Perioperative Care.

Endoscopic nasal septoplasty is a commonly performed otolaryngology procedure, not known to cause persistent postsurgical pain or hypersensitivity. Here, we discuss a unique case of persistent nasal pain that developed after a primary endoscopic septoplasty, which then progressed to marked mechanical and thermal allodynia following a revision septoplasty. Pain symptoms were found to be mediated by the maxillary division of the trigeminal nerve and resolved after percutaneous radiofrequency ablation (RFA) of bilateral maxillary nerves. To the best of our knowledge, this is the first report of maxillary nerve-mediated nasal allodynia after septoplasty.
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http://dx.doi.org/10.1213/XAA.0000000000001356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688083PMC
November 2020

Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head.

Stem Cell Res Ther 2020 11 11;11(1):480. Epub 2020 Nov 11.

National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, People's Republic of China.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH.

Methods: To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes.

Results: The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1.

Conclusions: This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.
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http://dx.doi.org/10.1186/s13287-020-01991-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656701PMC
November 2020

Clinical effectiveness of percutaneous vertebroplasty in conjunction with postoperative radiotherapy in the treatment of spinal metastases.

J Cancer Res Clin Oncol 2021 Mar 2;147(3):835-844. Epub 2020 Sep 2.

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian, 116001, Liaoning Province, China.

Purpose: This study aimed to evaluate the clinical effects of percutaneous vertebroplasty (PVP) combined with postoperative radiotherapy (RT) in the treatment of spinal metastases.

Methods: Nine patients (4 males and 5 females, mean age 59.56 years) with painful pathologic compression vertebral fractures caused by metastatic cancers of the spine (5 thoracic levels, 8 lumbar levels) were admitted to our hospital between July 17, 2016 and September 25, 2018. All patients were treated with PVP via bilateral pedicle approach combined with postoperative RT to treat metastatic lesions of the centrum. The clinical records of the patients were retrospectively analyzed. Patients' demographic features and medical conditions including the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Imageology data were observed.

Results: Patients' mean VAS scores decreased from 8.67 ± 0.50 preoperatively to 1.78 ± 0.83 at 6 months after PVP. Moreover, the mean ODI score decreased from 74.07 ± 13.15 preoperatively to 31.87 ± 10.00 at 6 months after PVP. Significant improvement in the degree of pain and dysfunction among the enrolled patients were observed. Furthermore, the metastatic carcinoma lesion within the vertebral body was well controlled according to imaging.

Conclusion: PVP in conjunction with postoperative RT is a good treatment strategy for vertebral compression fractures caused by metastases.
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http://dx.doi.org/10.1007/s00432-020-03371-yDOI Listing
March 2021

CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.

Haematologica 2021 Aug 1;106(8):2102-2113. Epub 2021 Aug 1.

3rd Medical Department, SCRI-LIMCR, Paracelsus Medical University, Cancer Cluster Salzburg.

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment.
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http://dx.doi.org/10.3324/haematol.2019.231944DOI Listing
August 2021

Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy.

J Diabetes Complications 2020 09 30;34(9):107641. Epub 2020 May 30.

Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.

Aims: To determine the associations between the levels of certain cytokines in the aqueous humor and the severity of diabetic retinopathy.

Methods: A total of 103 patients (one eye per patient) who received intravitreal injection with ranibizumab for diabetic retinopathy were enrolled and divided into 3 groups: nonproliferative diabetic retinopathy (NPDR) with macular edema group (42 eyes), proliferative diabetic retinopathy (PDR) group (40 eyes) and neovascular glaucoma due to PDR (NVG-PDR) group (21 eyes). The concentrations of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor were measured.

Results: In this study, 42, 40 and 21 patients (one eye per patient) were included in the NPDR, PDR and NVG-PDR groups, respectively. The median concentrations of IL-6, IL-8, IL-10, VEGF, TGF-β, VCAM-1, ICAM-1 and MCP-1 in the groups were measured. The levels of these 8 cytokines increased with the severity of diabetic retinopathy, especially in the NVG-PDR group. Compared with those in the NPDR group, the aqueous concentrations of these 8 cytokines were higher in the PDR group and were the highest in the NVG-PDR group. There were significant differences in all cytokines among the three groups (P < 0.05). Multivariate analysis showed that in the NPDR and PDR groups, the risk of PDR associated with elevated levels of TGF-β (P = 0.0004, OR 1.11, 95% CI [1.05-1.18]) and ICAM-1 (P = 0.0408, OR 10.75, 95% CI [1.10-104.61]). In the PDR and NVG groups, the risk of NVG associated with elevated levels of IL-10 (P = 0.0486, OR 0.7040, 95% CI [0.4966, 0.9979]), VEGF (P = 0.0279, OR 0.9963, 95% CI [0.9931, 0.9996]), and VCAM-1 (P = 0.0316, OR 0.9998, 95% CI [0.9996, 0.99998]). In the three groups, the risk of developing NVG associated with elevated levels of TGF-β (P < 0.001, OR 1.04, 95% CI [1.02, 1.05]).

Conclusions: The levels of these eight cytokines in the aqueous humor increased with the severity of diabetic retinopathy, especially in NVG-PDR. This study suggests that TGF-β, ICAM-1, IL-10, VEGF, and VCAM-1 may play a role in the progression of diabetic retinopathy, especially TGF-β, which may plays a significant role in NVG-PDR. These cytokines potentially may be used as biomarkers to predict the progress of diabetic retinopathy, contribute to the choice of treatment options and/or monitor treatment responses.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107641DOI Listing
September 2020

Combination of Ranibizumab with macular laser for macular edema secondary to branch retinal vein occlusion: one-year results from a randomized controlled double-blind trial.

BMC Ophthalmol 2020 Jun 19;20(1):241. Epub 2020 Jun 19.

Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: It is not clear whether macular laser combined with anti-vascular endothelial growth factor (VEGF) can reduce the number of anti-VEGF injections in the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Our study aimed to investigate the effects of intravitreal ranibizumab with or without macular laser for ME secondary to BRVO and its associated number of anti-VEGF injections.

Methods: This is a prospective, randomized, double-blind, monocentric trial.80 patients were enrolled and 64 patients fulfilled the study requirements. All patients received a minimum of 3 initial monthly ranibizumab injections, pro re nata (PRN) dosing thereafter VA and CRT stabilization criteria-driven PRN treatment. Laser was given 7 days after third ranibizumab injection in ranibizumab with laser group. The follow-up time of this study was 1 year. Best corrected visual acuity (BCVA) improvement, central retinal thickness (CRT) reduction and number of injections of patients were compared between two groups. T-test, non-parametric Wilcoxon test and chis-square tests were adopted for between-group comparisons.

Results: Thirty patients received intravitreal ranibizumab 0.5 mg alone and 34 patients received intravitreal ranibizumab 0.5 mg with macular laser. At 52 week, BCVA increased significantly and CRT decreased significantly in both groups (P < 0.001). However, there was no significant difference in BCVA improvement with baseline BCVA adjusted (p = 0.5226), and in the CRT reduction (P = 0.4552) between two groups after 52 weeks. There was also no significant difference in the number of injections between the two groups. (P = 0.0756). There was also no significant difference between ischemic and non-ischemic groups in BCVA improvement, CRT reduction and number of injections (P > 0.05).

Conclusions: Our study suggests that ranibizumab combined with macular laser is effective in the treatment of ME secondary to BRVO after 1 year of treatment with 3 + PRN regimen. However, combination of macular grid photocoagulation showed no beneficial anatomical or functional effect during follow-up period, nor did it reduce the number of ranibizumab injections, either in ischemic group or non-ischemic group. We suggest that there is no need to combine macular grid photocoagulation in the treatment of ME secondary to BRVO in the future.

Trial Registration: Clinical Trials NCT03054766. https://register.clinicaltrials.gov.Prospectively registered.
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http://dx.doi.org/10.1186/s12886-020-01498-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304204PMC
June 2020

Evaluate Air Pollution by Promethee Ranking in Yangtze River Delta of China.

Int J Environ Res Public Health 2020 01 16;17(2). Epub 2020 Jan 16.

School of Management Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, China.

A series of problems that are related to population, resources, environment, and ecology have emerged in recent years with the advancement of industrialization and urbanization in China. Especially, air pollution has become a severe trouble that directly endangers the health of residents. Accordingly, it is a need to make the assessment of air quality among cities, so that corresponding measures can be taken. For this purpose, ten major cities are selected as the research objects in Yangtze River Delta. Additionally, this study gathers and processes the data of five main air pollutants PM, PM, SO, O, and NO, respectively. Furthermore, the maximizing deviation method is used to obtain the respective weight of these pollutants and the preference ranking organization method for enrichment evaluations (PROMETHEE) is introduced into the assessment of air quality among ten cities. As a result, the ranking of air quality in Ningbo, Wenzhou, Shanghai, and Shaoxing was at the fore from 2014 to 2017. Meanwhile, the performance of Ningbo has always kept the top two and Shaoxing's ranking has risen since 2015. In addition, the air quality of Changzhou, Suzhou and Hangzhou was at an average level in the past four years. Moreover, the performance of Nanjing, Wuxi, and Zhenjiang was terrible when compared to other cities. Some useful suggestions have been proposed to control air quality based on the ranking results.
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http://dx.doi.org/10.3390/ijerph17020587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013759PMC
January 2020

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.

Nat Commun 2020 01 14;11(1):264. Epub 2020 Jan 14.

Department of Anatomy, University of California San Francisco, San Francisco, California, USA.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.
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http://dx.doi.org/10.1038/s41467-019-13839-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959328PMC
January 2020

Towards weakly-supervised focus region detection via recurrent constraint network.

IEEE Trans Image Process 2019 Sep 25. Epub 2019 Sep 25.

Recent state-of-the-art methods on focus region detection (FRD) rely on deep convolutional networks trained with costly pixel-level annotations. In this study, we propose a FRD method that achieves competitive accuracies but only uses easily obtained bounding box annotations. Box-level tags provide important cues of focus regions but lose the boundary delineation of the transition area. A recurrent constraint network (RCN) is introduced for this challenge. In our static training, RCN is jointly trained with a fully convolutional network (FCN) through box-level supervision. The RCN can generate a detailed focus map to locate the boundary of the transition area effectively. In our dynamic training, we iterate between fine-tuning FCN and RCN with the generated pixel-level tags and generate finer new pixel-level tags. To boost the performance further, a guided conditional random field is developed to improve the quality of the generated pixel-level tags. To promote further study of the weakly supervised FRD methods, we construct a new dataset called FocusBox, which consists of 5000 challenging images with bounding box-level labels. Experimental results on existing datasets demonstrate that our method not only yields comparable results than fully supervised counterparts but also achieves a faster speed.
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http://dx.doi.org/10.1109/TIP.2019.2942505DOI Listing
September 2019

Rapid Isolation of Dorsal Root Ganglion Macrophages.

J Vis Exp 2019 09 7(151). Epub 2019 Sep 7.

Department of Anesthesia and Perioperative Care, University of California San Francisco;

There are growing interests to study the molecular and cellular interactions among immune cells and sensory neurons in the dorsal root ganglia after peripheral nerve injury. Peripheral monocytic cells, including macrophages, are known to respond to a tissue injury through phagocytosis, antigen presentation, and cytokine release. Emerging evidence has implicated the contribution of dorsal root ganglia macrophages to neuropathic pain development and axonal repair in the context of nerve injury. Rapidly phenotyping (or "rapid isolation of") the response of dorsal root ganglia macrophages in the context of nerve injury is desired to identify the unknown neuroimmune factors. Here we demonstrate how our lab rapidly and effectively isolates macrophages from the dorsal root ganglia using an enzyme-free mechanical dissociation protocol. The samples are kept on ice throughout to limit cellular stress. This protocol is far less time consuming compared to the standard enzymatic protocol and has been routinely used for our Fluorescence-activated Cell Sorting analysis.
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http://dx.doi.org/10.3791/60023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778691PMC
September 2019

Mycobacterium marseillense Infection in Human Skin, China, 2018.

Emerg Infect Dis 2019 10;25(10):1991-1993

We describe a case of facial skin infection and sinusitis caused by Mycobacterium marseillense in an immunocompetent woman in China in 2018. The infection was cleared with clarithromycin, moxifloxacin, and amikacin. Antimicrobial drug treatments could not be predicted by genetic analyses; further genetic characterization would be required to do so.
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http://dx.doi.org/10.3201/eid2510.190695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759254PMC
October 2019

Gene expression profiles and bioinformatics analysis of insulin-like growth factor-1 promotion of osteogenic differentiation.

Mol Genet Genomic Med 2019 10 16;7(10):e00921. Epub 2019 Aug 16.

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.

Background: Insulin-like growth factor-1 (IGF-1) promotes osteoblast differentiation and mineralization. The objective of this study was to investigate the effects of IGF-1 on proliferation, mineralization, alkaline phosphatase (ALP) synthesis, and gene expression of osteoblast differentiation in MC3T3-E1 osteoblasts cells, and to explore gene expression profiling differential genes.

Methods: MC3T3-E1 osteoblasts cells were cultured in medium with or without IGF-1. The ALP assay was employed to determine the osteoblast mineralization, and Alizarin red S to stain for calcium deposits, which were the indicators of mature osteocytes. The living cell number was assessed by the Cell Counting Kit-8 method. RNA-seq analysis was applied to identify genes that were differentially expressed in with or without IGF-1 as well as genes that varied between these two groups. The expression of osteogenic marker genes was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis.

Result: The cell number of osteoblasts exposed to IGF-1 at 200 μg/L significantly increased compared with the control group. The ALP activity in IGF-1-treated cells was higher than that in the control group. IGF-1 can increase ALP synthesis in osteoblasts in vitro. RNA-seq analysis showed that 677 triggered differentially expressed genes by IGF, of which 383 genes were downregulated and 294 genes were upregulated. Gene ontology (GO) analysis showed that IGF-1 caused a significant change in gene expression patterns.

Conclusions: This result suggested that IGF-1 could probably promote the synthesis of organic matrix and mineralize action of bone. Osteogenic-related genes (DMP1, PHEX, SOST, BMP2, RUNX2, OPN, and OCN) were significantly upregulated both in GO analysis and in pathway analysis to perform qRT-PCR. Western blot analysis demonstrated that the Notch pathway was highly upregulated in MC3T3-E1 cells.
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http://dx.doi.org/10.1002/mgg3.921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082822PMC
October 2019

Therapeutic effects of ranibizumab in patients with polypoidal choroidal vasculopathy.

BMC Ophthalmol 2019 Jul 19;19(1):153. Epub 2019 Jul 19.

Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, No.1 Dahua Road, Dongdan, Dongcheng District, Beijing, China.

Background: There is no consensus on the optimal initial treatment for polypoidal choroidal vasculopathy (PCV). Our study aimed to report the efficacy of repeated injections of intravitreal ranibizumab with or without photodynamic therapy for the treatment of PCV and to determine the possible factors predictive of visual outcomes.

Methods: The results of the initial treatment of 40 patients with PCV with 3 monthly injections of ranibizumab were retrospectively reviewed. We compared the results in terms of the best corrected visual acuity (BCVA), the central retinal thickness (CRT), the number of injections, the regression rates of polyps and the rates of the reduction of subretinal fluid.

Results: At the 3-month follow-up, the mean BCVA was significantly increased by 7.3 ± 12.4 letters compared to baseline (p < 0.01). At the 12-month follow-up, the mean BCVA was increased by 3.4 ± 15.4 letters compared to baseline, and there was no significant difference (p > 0.05). The mean CRT at the 12-month follow-up was 593.58 ± 243.64 μm, with an average decrease of 101.55 ± 256.07 μm compared to baseline (p < 0.01). Fifteen eyes (18.8%) showed the complete regression of polyps, and 22 eyes (27.5%) showed a reduction in polyps. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were significant independent factors that were predictive of improved VA at the final follow-up.

Conclusions: Three monthly injections of ranibizumab as an initial treatment could significantly improve VA in PCV patients in the short term. At 12 months postinjection, ranibizumab treatment could stabilize VA in most PCV patients. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were predictive factors for the relative improvement of VA at the final follow-up.
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http://dx.doi.org/10.1186/s12886-019-1156-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642544PMC
July 2019

Evaluate Typhoon Disasters in 21st Century Maritime Silk Road by Super-Efficiency DEA.

Int J Environ Res Public Health 2019 05 8;16(9). Epub 2019 May 8.

School of Management Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, China.

The Belt and Road Initiative involves many countries and areas. As the introducer, China plays a key role in the initiative. However, the coastal areas in China have frequently been hit by typhoons that lead to huge casualties and economic losses. In order to reduce damages caused by natural disasters, this paper selected the coastal regions of the 21st Century Maritime Silk Road as the study areas, specifically Shanghai, Zhejiang, Guangdong, Fujian, and Hainan, to estimate the vulnerability to typhoon disasters based on the historical data about typhoon disasters and the super-efficiency data envelopment analysis (DEA) evaluation model. Although Shanghai is a low-vulnerable region, it needs to pay close attention to the risk of typhoon disasters due to the outstanding economic influence. In addition, it was found that the vulnerability to typhoons in Zhejiang, Guangdong, and Hainan showed a dramatic fluctuation from 2011 to 2016, and Zhejiang's vulnerability in 2013 was extremely high compared to other years. Meanwhile, Guangdong and Hainan are highly vulnerable areas, suffering from typhoon disasters heavily. Moreover, the vulnerability to typhoons for Fujian is relatively low.
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http://dx.doi.org/10.3390/ijerph16091614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539588PMC
May 2019

TGF‑β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway.

Mol Med Rep 2019 May 18;19(5):3505-3518. Epub 2019 Mar 18.

Department of Orthopaedics, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.

Transforming growth factor β1 (TGF‑β1) has been suggested to be a candidate cytokine in the field of bone tissue engineering. Cytokines serve important roles in tissue engineering, particularly in the repair of bone damage; however, the underlying molecular mechanisms remain unclear. In the present study, the effects of TGF‑β1 on the osteogenesis and motility of hFOB1.19 human osteoblasts were demonstrated via the phenotype and gene expression of cells. Additionally, the role of the phosphatidylinositol 3‑kinase/protein kinase B/mammalian target of rapamycin/S6 kinase 1 (PI3K/AKT/mTOR/S6K1) signalling pathway in the effects of TGF‑β1 on osteoblasts was investigated. It was demonstrated using Cell Counting Kit‑8 and flow cytometry assays that the proliferation of human osteoblasts was promoted by 1 ng/ml TGF‑β1. In addition, alkaline phosphatase activity, Alizarin red staining, scratch‑wound and Transwell assays were conducted. It was revealed that osteogenesis and the migration of cells were regulated by TGF‑β1 via the upregulation of osteogenic and migration‑associated genes. Alterations in the expression of osteogenesis‑ and migration‑associated genes were evaluated following pre‑treatment with a PI3K/AKT inhibitor (LY294002) and an mTOR/S6K1 inhibitor (rapamycin), with or without TGF‑β1. The results indicated that TGF‑β1 affected the osteogenesis and mineralisation of osteoblasts via the PI3K/AKT signalling pathway. Furthermore, TGF‑β1 exhibited effects on mTOR/S6K1 downstream of PI3K/AKT. The present study demonstrated that TGF‑β1 promoted the proliferation, differentiation and migration of human hFOB1.19 osteoblasts, and revealed that TGF‑β1 affected the biological activity of osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway. Our findings may provide novel insight to aid the development of bone tissue engineering methods for the treatment of bone injury.
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http://dx.doi.org/10.3892/mmr.2019.10051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471541PMC
May 2019

SIRT1 inhibits apoptosis in in vivo and in vitro models of spinal cord injury via microRNA-494.

Int J Mol Med 2019 Apr 22;43(4):1758-1768. Epub 2019 Feb 22.

Department of Orthopaedics, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.

The aim of the present study was to investigate the function and mechanism of sirtuin 1 (SIRT1) in spinal cord injury (SCI). Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression levels of microRNA (miR)‑494. MTT assay, lactate dehydrogenase activity assay and flow cytometry were used to analyze the effects of miR‑494 on cell growth and apoptosis in a model of SCI. The present study demonstrated that SIRT1 expression was reduced; whereas miR‑494 expression was increased in a rat model of SCI. Overexpression of miR‑494 suppressed the protein expression levels of SIRT1, and induced p53 protein expression. Conversely, knockdown of miR‑494 induced SIRT1 protein expression in an in vitro model of SCI. Furthermore, overexpression of miR‑494 promoted cell apoptosis and decreased cell growth in an in vitro model of SCI; however, miR‑494 knockdown enhanced cell growth and inhibited cell apoptosis. Administration of a SIRT1 agonist reduced the effects of miR‑494 overexpression on cell apoptosis in an SCI model, whereas treatment with a p53 agonist reduced the effects of miR‑494 knockdown on cell apoptosis in an SCI model. Together, these findings suggested that SIRT1 may inhibit apoptosis of SCI in vivo and in vitro through the p53 signaling pathway, whereas miR‑494 suppressed SIRT1 and induced apoptosis.
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http://dx.doi.org/10.3892/ijmm.2019.4106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414168PMC
April 2019

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods.

J Cell Biochem 2019 Jan 17. Epub 2019 Jan 17.

Department of Orthopaedics, Zhongshan Hospital of Dalian University, Dalian, China.

Spinal cord injury (SCI) is characterized by dramatic neurons loss and axonal regeneration suppression. The underlying mechanism associated with SCI-induced immune suppression is still unclear. Weighted gene coexpression network analysis (WGCNA) is now widely applied for the identification of the coexpressed modules, hub genes, and pathways associated with clinic traits of diseases. We performed this study to identify hub genes associated with SCI development. Gene Expression Omnibus (GEO) data sets GSE45006 and GSE20907 were downloaded and the significant correlativity and connectivity between them were detected using WGCNA. Three significant consensus modules, including 567 eigengenes, were identified from the master GSE45006 data following the preconditions of approximate scale-free topology for WGCNA. Further bioinformatics analysis showed these eigengenes were involved in inflammatory and immune responses in SCI. Three hub genes Rac2, Itgb2, and Tyrobp and one pathway "natural killer cell-mediated cytotoxicity" were identified following short time-series expression miner, protein-protein interaction network, and functional enrichment analysis. Gradually upregulated expression patterns of Rac2, Itgb2, and Tyrobp genes at 0, 3, 7, and 14 days after SCI were confirmed based on GSE45006 and GSE20907 data set. Finally, we found that Rac2, Itgb2, and Tyrobp genes might take crucial roles in SCI development through the "natural killer cell-mediated cytotoxicity" pathway.
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http://dx.doi.org/10.1002/jcb.27908DOI Listing
January 2019

Efficacy and Safety of Pregabalin in Neuropathic Pain Followed Spinal Cord Injury: A Review and Meta-Analysis of Randomized Controlled Trials.

Clin J Pain 2019 03;35(3):272-278

Department of Orthopaedics.

Objective: Pregabalin has been approved for the treatment of the neuropathic pain following spinal cord injury (SCI). We performed a systemic review and meta-analysis of randomized, controlled, multicenter trials to evaluate the efficacy and safety of pregabalin for SCI-induced neuropathic pain.

Materials And Methods: Research searching was performed in PubMed and EMBASE databases and the Cochrane library in May 2018. Clinical controlled trials using pregabalin for the pain treatment following SCI in adults (18 y old and above) were included. Pain and safety-related adverse events were considered as outcomes. Meta-analysis was conducted using Revman 5.0 software.

Results: Five publications (pregabalin, patients=261, placebo, patients=216) were included in our study. After at least 4-week's treatment with pregabalin (flexible dose, 150 to 600 mg/d), pregabalin-treated patients showed reduced pain -1.54, 95% confidence interval (CI) (-2.33, -0.75), P=0.0001; improved >30% 1.83, 95% CI (1.37, 2.46), P<0.0001 and >50% pain relief 2.40, 95% CI (1.53, 3.77), P=0.0001; increased adverse events 1.36, 95% CI (1.18, 1.577), P<0.0001; and reduced Hospital Anxiety and Depression Scale - anxiety -1.50, 95% CI (-2.99, -0.00), P=0.05 and - depression -0.34, 95% CI (-0.55, -0.12), P=0.002 scores compared with placebo-treated patients. Stratified meta-analysis showed there was no difference in primary adverse events (drowsiness, dizziness, peripheral edema, and dry mouth) between pregabalin and placebo groups (P≥0.05).

Conclusions: Our results showed pregabalin was efficacious and might be safe treatment for chronic pain followed SCI.
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http://dx.doi.org/10.1097/AJP.0000000000000675DOI Listing
March 2019

Study of engineered low-modulus Mg/PLLA composites as potential orthopaedic implants: An in vitro and in vivo study.

Colloids Surf B Biointerfaces 2019 Feb 23;174:280-290. Epub 2018 Oct 23.

Department of Orthopaedics, Zhongshan Hospital of Dalian University, Dalian, 116001, China.

Low molecular weight poly-lactic acid (PLLA) is a polymer matrix of orthopaedic implants. The PLLA matrix incorporating bioactive magnesium ion (Mg) enhances bone regeneration. But the optimal ratio of Mg to PLLA matrix has not been well reported and is worthy of study. We synthesized silane-coated Mg/PLLA composites containing 1%, 2%, 3%, 4% and 5% Mg micro-particles. The mechanical properties, in vitro cytocompatibility, cell viability and osteogenesis differentiation and in vivo performance of silane-coated Mg/PLLA composites were evaluated. These results showed that the bending and tensile strength of PLLA matrix was reduced by incorporation of Mg micro-particles. Mg/PLLA composites with higher Mg micro-particles ratio showed higher Mg leaching rate and pH value in immersion solutions. MC3T3-E1 pre-osteoblasts incubated with Mg/PLLA composites containing higher ratio of Mg micro-particles showed higher cytocompatibility, cell viability, osteogenesis differentiation and migration. In vitro cellular responses showed that MC3T3-E1 pre-osteoblasts had the highest cell viability at 50 ppm Mg. In vivo animal studies showed there was no change in serum Mg concentration after implanting Mg/PLLA composites comparing with control and the implants of silane-coated Mg/PLLA composites accelerated bone formation. In summary, our study revealed the feasibility of silane-coated Mg/PLLA composites as orthopaedic implants. Silane-coated Mg/PLLA composites with Mg micro-particles ratio of 3% ∼ 5% were optimal substitutes for bone regeneration.
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http://dx.doi.org/10.1016/j.colsurfb.2018.10.054DOI Listing
February 2019

Integrating Patient-Controlled Analgesia Using Implanted Intrathecal Pumps for Postoperative Pain Management: A Case Report.

A A Pract 2018 Jun;10(11):285-287

From the Department of Anesthesia and Perioperative Care.

Intrathecal patient-controlled analgesia (IT-PCA) through implanted intrathecal infusion pumps has been increasingly utilized for severe cancer and chronic noncancer pain management. However, its application for acute postoperative pain management has not been reported to date. We present a case of a patient with an implanted intrathecal pump for chronic nonmalignant back pain who underwent an extensive spinal fusion surgery. The IT-PCA functionality of her intrathecal pump was successfully integrated into her postoperative multimodal pain regimen. Hence, IT-PCA can be safely incorporated into acute postoperative pain management with vigilant monitoring and close multidisciplinary collaboration.
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http://dx.doi.org/10.1213/XAA.0000000000000685DOI Listing
June 2018
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