Publications by authors named "Bobin Mi"

71 Publications

Finite element analysis of different fixation methods of screws on absorbable plate for rib fractures.

Front Bioeng Biotechnol 2022 22;10:960310. Epub 2022 Jul 22.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Multiple rib fractures caused by trauma are common injuries and the internal fixation methods of these injuries have been paid more and more attention by surgeons. Absorbable plates and screws are the effective way to treat rib fractures, but there are no reports on which type of screw fixation method is most effective. In this study, finite element analysis was used to study the effects of five different types of screw fixation methods on anterior rib, lateral rib and posterior rib. The finite element model of the ribs was reconstructed from CT images, and the internal pressure (40 kPa) and intercostal force (30 N) on the surfaces of the ribs were simulated accordingly. An intercostal force of 30 N was applied to the upper and lower surfaces of the ribs to simulate the effect of intercostal muscle force. The pressure of 40 kPa was applied to the inner surface of the ribs, and the normal direction was applied to the inner surface of the ribs. The positive direction was considered inspiratory pressure, and the negative direction was considered expiratory pressure. The results indicate the optimal type of screw fixation on the absorbable plate for rib fractures, and provide a basis and reference for clinical application.
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http://dx.doi.org/10.3389/fbioe.2022.960310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354002PMC
July 2022

The Regulatory Role of Ferroptosis in Bone Homeostasis.

Stem Cells Int 2022 13;2022:3568597. Epub 2022 Jul 13.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Ferroptosis is an iron-dependent form of programmed cell death and an important type of biological catabolism. Through the action of divalent iron or ester oxygenase, ferroptosis can induce lipid peroxidation and cell death, regulating a variety of physiological processes. The role of ferroptosis in the modulation of bone homeostasis is a significant topic of interest. Herein, we review and discuss recent studies exploring the mechanisms and functions of ferroptosis in different bone-related cells, including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. The association between ferroptosis and disorders of bone homeostasis is also explored in this review. Overall, we aim to provide a detailed overview of ferroptosis, summarizing recent understanding on its role in regulation of bone physiology and bone disease pathogenesis.
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http://dx.doi.org/10.1155/2022/3568597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300333PMC
July 2022

Injectable Bacteria-Sensitive Hydrogel Promotes Repair of Infected Fractures via Sustained Release of miRNA Antagonist.

ACS Appl Mater Interfaces 2022 Aug 22;14(30):34427-34442. Epub 2022 Jul 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Fracture nonunion can result in considerable physical harm and limitation of quality of life in patients, exerting an extensive economic burden to the society. Nonunion largely results from unresolved inflammation and impaired osteogenesis. Despite advancements in surgical techniques, the indispensable treatment for nonunion is robust anti-inflammation therapy and the promotion of osteogenic differentiation. Herein, we report that plasma exosomes derived from infected fracture nonunion patients (Non-Exos) delayed fracture repair in mice by inhibiting the osteogenic differentiation of bone marrow stromal cells in vivo and in vitro. Unique molecular identifier microRNA-sequencing (UID miRNA-seq) suggested that microRNA-708-5p (miR-708-5p) was overexpressed in Non-Exos. Mechanistically, miR-708-5p targeted structure-specific recognition protein 1, thereby suppressing the Wnt/β-catenin signaling pathway, which, in turn, impaired osteogenic differentiation. AntagomicroRNA-708-5p (antagomiR-708-5p) could partly reverse the above process. A bacteria-sensitive natural polymer hyaluronic-acid-based hydrogel (HA hydrogel) loaded with antagomiR-708-5p exhibited promising effects in an in vivo study through antibacterial and pro-osteogenic differentiation functions in infected fractures. Overall, the effectiveness and reliability of an injectable bacteria-sensitive hydrogel with sustained release of agents represent a promising approach for infected fractures.
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http://dx.doi.org/10.1021/acsami.2c08491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354009PMC
August 2022

Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold.

Bioact Mater 2022 Dec 2;18:552-568. Epub 2022 Jun 2.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA; QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold ([email protected]/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.
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http://dx.doi.org/10.1016/j.bioactmat.2022.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256949PMC
December 2022

MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2.

Exp Mol Med 2022 Jul 13;54(7):961-972. Epub 2022 Jul 13.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.

MicroRNAs (miRNAs) broadly regulate normal biological functions of bone and the progression of fracture healing and osteoporosis. Recently, it has been reported that miR-1224-5p in fracture plasma is a potential therapy for osteogenesis. To investigate the roles of miR-1224-5p and the Rap1 signaling pathway in fracture healing and osteoporosis development and progression, we used BMMs, BMSCs, and skull osteoblast precursor cells for in vitro osteogenesis and osteoclastogenesis studies. Osteoblastogenesis and osteoclastogenesis were detected by ALP, ARS, and TRAP staining and bone slice resorption pit assays. The miR-1224-5p target gene was assessed by siRNA-mediated target gene knockdown and luciferase reporter assays. To explore the Rap1 pathway, we performed high-throughput sequencing, western blotting, RT-PCR, chromatin immunoprecipitation assays and immunohistochemical staining. In vivo, bone healing was judged by the cortical femoral defect, cranial bone defect and femoral fracture models. Progression of osteoporosis was evaluated by an ovariectomy model and an aged osteoporosis model. We discovered that the expression of miR-1224-5p was positively correlated with fracture healing progression. Moreover, in vitro, overexpression of miR-1224-5p slowed Rankl-induced osteoclast differentiation and promoted osteoblast differentiation via the Rap1-signaling pathway by targeting ADCY2. In addition, in vivo overexpression of miR-1224-5p significantly promoted fracture healing and ameliorated the progression of osteoporosis caused by estrogen deficiency or aging. Furthermore, knockdown of miRNA-1224-5p inhibited bone regeneration in mice and accelerated the progression of osteoporosis in elderly mice. Taken together, these results identify miR-1224-5p as a key bone osteogenic regulator, which may be a potential therapeutic target for osteoporosis and fracture nonunion.
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http://dx.doi.org/10.1038/s12276-022-00799-9DOI Listing
July 2022

Emerging Insight Into the Role of Circadian Clock Gene BMAL1 in Cellular Senescence.

Front Endocrinol (Lausanne) 2022 6;13:915139. Epub 2022 Jun 6.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cell senescence is a crucial process in cell fate determination and is involved in an extensive array of aging-associated diseases. General perceptions and experimental evidence point out that the decline of physical function as well as aging-associated diseases are often initiated by cell senescence and organ ageing. Therefore, regulation of cell senescence process can be a promising way to handle aging-associated diseases such as osteoporosis. The circadian clock regulates a wide range of cellular and physiological activities, and many age-linked degenerative disorders are associated with the dysregulation of clock genes. BMAL1 is a core circadian transcription factor and governs downstream genes by binding to the E-box elements in their promoters. Compelling evidence has proposed the role of BMAL1 in cellular senescence and aging-associated diseases. In this review, we summarize the linkage between BMAL1 and factors of cell senescence including oxidative stress, metabolism, and the genotoxic stress response. Dysregulated and dampened BMAL1 may serve as a potential therapeutic target against aging- associated diseases.
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http://dx.doi.org/10.3389/fendo.2022.915139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207346PMC
June 2022

SHIP1 Activator AQX-1125 Regulates Osteogenesis and Osteoclastogenesis Through PI3K/Akt and NF-κb Signaling.

Front Cell Dev Biol 2022 4;10:826023. Epub 2022 Apr 4.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

With the worldwide aging population, the prevalence of osteoporosis is on the rise, particularly the number of postmenopausal women with the condition. However, the various adverse side effects associated with the currently available treatment options underscore the need to develop novel therapies. In this study, we investigated the use of AQX-1125, a novel clinical-stage activator of inositol phosphatase-1 (SHIP1), in ovariectomized (OVX) mice, identifying a protective role. We then found that the effect was likely due to increased osteogenesis and mineralization and decreased osteoclastogenesis caused by AQX-1125 in a time- and dose-dependent manner. The effect against OVX-induced bone loss was identified to be SHIP1-dependent as pretreatment of BMSCs and BMMs with SHIP1 RNAi could greatly diminish the osteoprotective effects. Furthermore, SHIP1 RNAi administration induced significant bone loss and decreased bone mass. Mechanistically, AQX-1125 upregulated the expression level and activity of SHIP1, followed upregulating the phosphorylation levels of PI3K and Akt to promote osteoblast-related gene expressions, including Alp, cbfa1, Col1a1, and osteocalcin (OCN). NF-κB signaling was also inhibited through suppression of the phosphorylation of IκBα and P65 induced by RANKL, resulting in diminished osteoclastogenesis. Taken together, our results demonstrate that AQX-1125 may be a promising candidate for preventing and treating bone loss.
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http://dx.doi.org/10.3389/fcell.2022.826023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014098PMC
April 2022

Operative treatment outcomes of anterior sternoclavicular joint dislocation using two experimental methods - an acromioclavicular joint hook plate versus a locking plate: a retrospective study.

BMC Musculoskelet Disord 2022 Apr 11;23(1):350. Epub 2022 Apr 11.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, People's Republic of China.

Background: We aimed to compare the intraoperative and early postoperative clinical outcomes of using an acromioclavicular joint hook plate (AJHP) versus a locking plate (LP) in the treatment of anterior sternoclavicular joint dislocation.

Methods: Seventeen patients with anterior sternoclavicular joint dislocation were retrospectively analyzed from May 2014 to September 2019. Six patients were surgically treated with an AJHP, and 11 were surgically treated with an LP. Five male and one female patients composed the AJHP group, and nine male and two female patients composed the LP group. The mean age of all patients was 49.5 years.

Results: Reduction and fixation were performed with AJHP or LP in all 17 patients. The mean operative blood loss, operative time, and length of incision in the AJHP group were significantly better than those in the LP group. Shoulder girdle movement of the AJHP group was significantly better than that of the LP group.

Conclusions: This study revealed that AJHP facilitated glenohumeral joint motion, reduced the risk of rupture of mediastinal structures, required a shorter incision, and had lesser blood loss and a shorter duration of operation compared with LP. However, some deficiencies require further improvement.
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http://dx.doi.org/10.1186/s12891-022-05293-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996669PMC
April 2022

Recent Advances in Enhancement Strategies for Osteogenic Differentiation of Mesenchymal Stem Cells in Bone Tissue Engineering.

Front Cell Dev Biol 2022 23;10:824812. Epub 2022 Feb 23.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Although bone is an organ that displays potential for self-healing after damage, bone regeneration does not occur properly in some cases, and it is still a challenge to treat large bone defects. The development of bone tissue engineering provides a new approach to the treatment of bone defects. Among various cell types, mesenchymal stem cells (MSCs) represent one of the most promising seed cells in bone tissue engineering due to their functions of osteogenic differentiation, immunomodulation, and secretion of cytokines. Regulation of osteogenic differentiation of MSCs has become an area of extensive research over the past few years. This review provides an overview of recent research progress on enhancement strategies for MSC osteogenesis, including improvement in methods of cell origin selection, culture conditions, biophysical stimulation, crosstalk with macrophages and endothelial cells, and scaffolds. This is favorable for further understanding MSC osteogenesis and the development of MSC-based bone tissue engineering.
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http://dx.doi.org/10.3389/fcell.2022.824812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904963PMC
February 2022

Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant.

Bioact Mater 2022 Jul 3;13:300-311. Epub 2021 Nov 3.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation. Over-active and continuous inflammation, however, impairs fracture healing and leads to excessive tissue damage. Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site. In the present study, we achieved an enriched concentration of PD-L1 from exosomes (Exos) of a genetically engineered Human Umbilical Vein Endothelial Cell (HUVECs), and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface, suppressing the activation of T cells. Furthermore, exosomal PD-L1 induced Mesenchymal Stem Cells (MSCs) towards osteogenic differentiation when pre-cultured with T cells. Moreover, embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner. Additionally, exosomal PD-L1, embedded in a hydrogel, markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase. Importantly, our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites, while T cells in distant immune organs such as the spleen were not affected. In summary, this study provides the first example of using PD-L1-enriched Exos for bone fracture repair, and highlights the potential of [email protected] systems for bone fracture therapy through immune inhibitory effects.
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http://dx.doi.org/10.1016/j.bioactmat.2021.10.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844834PMC
July 2022

Clinical Application Study of Minimally Invasive Double-Reverse Traction in Complex Tibial Plateau Fractures.

Biomed Res Int 2022 22;2022:5564604. Epub 2022 Jan 22.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022 Hubei, China.

The aim of this study was to evaluate the clinical application of double-reverse traction for minimally invasive reduction of complex tibial plateau fractures. A retrospective analysis was performed to identify all patients admitted to the Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from March 2017 to December 2019 with Schatzker type VI tibial plateau fractures. 12 patients were identified (7 men and 5 women) with an average age of 46.15 ± 13 (39-58) years old. All patients were treated with double-reverse traction and closed reduction. After the fracture was reduced, the bone plate was fixed by percutaneous minimally invasive implantation. Outcomes assessed in this study include operation time and intraoperative blood loss. Imaging was performed during the postoperative follow-up, and functional recovery was evaluated at the final follow-up according to the Hospital for Special Surgery (HSS) score and the International Knee Joint Literature Committee (IKDC) functional score. Patients were followed up for 12.54 ± 1.5 (8-15) months. The average operation time was 63.63 ± 21 (35-120) minutes, and the average intraoperative blood loss was 105.45 ± 21 (60-200) mL. The Rasmussen imaging score was either excellent or good in all cases. The knee joint HSS score was 86.15 ± 6 (79-90) points, and the IKDC score was 80.01 ± 11 (75-90) points. No complications, such as wound infection, incision disunion, loosening of internal fixation, and internal fixation failure, occurred. In the treatment of Schatzker VI type complex tibial plateau fracture, the dual-reverse traction minimally invasive technique has the advantages of safety and effectiveness, less soft tissue injury, and allowing early joint movement, which is worthy of clinical promotion.
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http://dx.doi.org/10.1155/2022/5564604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800596PMC
March 2022

Osteoblast/Osteoclast and Immune Cocktail Therapy of an Exosome/Drug Delivery Multifunctional Hydrogel Accelerates Fracture Repair.

ACS Nano 2022 Jan 3. Epub 2022 Jan 3.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

The osteoblast/osteoclast and M1/M2 macrophage ratios play critical roles in delayed fracture healing. Robust osteoblast differentiation and M2 macrophage polarization can substantiality promote fracture repair; however, the combined effect of these strategies has not been previously studied. In this study, we constructed a cocktail therapy to simultaneously regulate the osteoblast/osteoclast and M1/M2 macrophage balance. The cocktail therapy composed of a natural polymer hyaluronic-acid-based hydrogel (HA hydrogel, which has a tissue-adhesive, injectable, self-healing, anti-inflammation profile), engineered endothelial cell-derived exosomes (EC-Exos), and APY29, an IRE-1α inhibitor. This allowed for specific delivery of EC-Exos and APY29 for osteoblast/osteoclast and macrophage regulation, respectively. The results suggested that the cocktail therapy exerted pro-fracture repair effects with each of its components established as indispensable. The assessed cocktail therapy provides insight into synergistic strategies and is useful for developing more suitable pro-fracture repair therapy.
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http://dx.doi.org/10.1021/acsnano.1c08284DOI Listing
January 2022

Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing.

ACS Appl Mater Interfaces 2021 Dec 19;13(48):56944-56960. Epub 2021 Nov 19.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

The immune system and skeletal system are closely linked. Macrophages are one of the most important immune cells for bone remodeling, playing a prohealing role mainly through M2 phenotype polarization. Baicalein (5,6,7-trihydroxyflavone, BCL) has been well documented to have a noticeable promotion effect on M2 macrophage polarization. However, due to the limitations in targeted delivery to macrophages and the toxic effect on other organs, BCL has rarely been used in the treatment of bone fractures. In this study, we developed mesoporous silica and FeO composite-targeted nanoparticles loaded with BCL ([email protected]), which could be magnetically delivered to the fracture site. This induced macrophage recruitment in a targeted manner, polarizing them toward the M2 phenotype, which was demonstrated to induce mesenchymal stem cells (MSCs) toward osteoblastic differentiation. The mesoporous silicon nanoparticles (MSNs) were prepared with surface sulfhydrylation and amination modification, and the mesoporous channels were blocked with β-cyclodextrin. The outer layer of the mesoporous silicon was added with an amantane-modified NW-targeting peptide to obtain the targeted nanosystem. After entering macrophages, BCL could be released from nanoparticles since the disulfide linker could be cleaved by intracellular glutathione (GSH), resulting in the removal of cyclodextrin (CD) gatekeeper, which is a key element in the pro-bone-remodeling functions such as anti-inflammation and induction of M2 macrophage polarization to facilitate osteogenic differentiation. This nanosystem passively accumulated in the fracture site, promoting osteogenic differentiation activities, highlighting a potent therapeutic benefit with high biosafety.
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http://dx.doi.org/10.1021/acsami.1c17420DOI Listing
December 2021

All-in-One: Multifunctional Hydrogel Accelerates Oxidative Diabetic Wound Healing through Timed-Release of Exosome and Fibroblast Growth Factor.

Small 2022 01 17;18(1):e2104229. Epub 2021 Nov 17.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.

The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug-resistant bacterial infections, angiopathy, and oxidative damage to the microenvironment. Herein, a novel in situ injectable [email protected] /FGF-2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long-term antibacterial protection. The MnO /ε-PL nanosheet is able to catalyze the excess H O produced in the wound, converting it to O , thus not only eliminating the harmful effects of H O but also providing O for wound healing. Moreover, the release of M2-derived Exosomes (M2 Exos) and FGF-2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the [email protected] /FGF-2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.
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http://dx.doi.org/10.1002/smll.202104229DOI Listing
January 2022

Polydatin Ameliorates Osteoporosis via Suppression of the Mitogen-Activated Protein Kinase Signaling Pathway.

Front Cell Dev Biol 2021 29;9:730362. Epub 2021 Sep 29.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Polydatin (POL) is a natural active compound found in with reported anti-oxidant and antiviral effects. With the aging population there has been a stark increase in the prevalence of osteoporosis (OP), rendering it an imposing public health issue. The potential effect of POL as a therapy for OP remains unclear. Therefore, we sought to investigate the therapeutic effect of POL in OP and to elucidate the underlying signaling mechanisms in its regulatory process. The POL-targeted genes interaction network was constructed using the Search Tool for Interacting Chemicals (STITCH) database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways involved in OP and POL-targeted genes were identified. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the osteogenic genes and the phosphorylation level in pre-osteoblastic cells. In addition, ALP and alizarin red staining was used to test the effect of POL on extracellular matrix mineralization. Twenty-seven KEGG pathways shared between POL-related genes and OP were identified. signaling was identified as a potential key mechanism. results highlighted a definitive anti-OP effect of POL. The phosphorylation levels of signaling, including α, , and , were significantly decreased in this regulatory process. Our results suggest that POL has a promising therapeutic effect in OP. signaling may be the underlying mechanism in this effect, providing a novel sight in discovering new drugs for OP.
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http://dx.doi.org/10.3389/fcell.2021.730362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511501PMC
September 2021

Nomogram for Predicting Deep Venous Thrombosis in Lower Extremity Fractures.

Biomed Res Int 2021 22;2021:9930524. Epub 2021 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277#, Wuhan, 430022 Hubei, China.

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability.
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http://dx.doi.org/10.1155/2021/9930524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245242PMC
October 2021

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing.

Front Bioeng Biotechnol 2021 24;9:707479. Epub 2021 Jun 24.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.
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http://dx.doi.org/10.3389/fbioe.2021.707479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264455PMC
June 2021

Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis.

J Nanobiotechnology 2021 May 21;19(1):150. Epub 2021 May 21.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing.

Results: We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing.

Conclusions: PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.
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http://dx.doi.org/10.1186/s12951-021-00894-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139165PMC
May 2021

SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing.

Int J Biol Sci 2021 25;17(5):1277-1288. Epub 2021 Mar 25.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both and . Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation . Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.
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http://dx.doi.org/10.7150/ijbs.56657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040480PMC
May 2021

The effectiveness and safety of LMWH for preventing thrombosis in patients with spinal cord injury: a meta-analysis.

J Orthop Surg Res 2021 Apr 14;16(1):262. Epub 2021 Apr 14.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277#, Wuhan, 430022, Hubei, P. R. China.

Background: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined.

Materials And Methods: Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3.

Results: A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42-4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55-1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found.

Conclusions: The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments.
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http://dx.doi.org/10.1186/s13018-021-02412-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048068PMC
April 2021

Correction to: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3.

J Nanobiotechnology 2021 Mar 27;19(1):88. Epub 2021 Mar 27.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1186/s12951-021-00828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004442PMC
March 2021

miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP/PI3K-AKT inhibition.

Mol Ther Nucleic Acids 2021 Mar 15;23:1345-1359. Epub 2021 Feb 15.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Patients who sustain concomitant fractures and traumatic brain injury (TBI) are known to have significantly quicker fracture-healing rates than patients with isolated fractures. The mechanisms underlying this phenomenon have yet to be identified. In the present study, we found that the upregulation of microRNA-92a-3p (miRNA-92a-3p) induced by TBI correlated with a decrease in integrin binding sialoprotein (IBSP) expression in callus formation. , overexpressing miRNA-92a-3p inhibited IBSP expression and accelerated osteoblast differentiation, whereas silencing of miRNA-92a-3p inhibited osteoblast activity. A decrease in IBSP facilitated osteoblast differentiation via the Phosphatidylinositol 3-kinase/threonine kinase 1 (PI3K/AKT) signaling pathway. Through luciferase assays, we found evidence that IBSP is a miRNA-92a-3p target gene that negatively regulates osteoblast differentiation. Moreover, the present study confirmed that pre-injection of agomiR-92a-3p leads to increased bone formation. Collectively, these results indicate that miRNA-92a-3p overexpression may be a key factor underlying the improved fracture healing observed in TBI patients. Upregulation of miRNA-92a-3p may therefore be a promising therapeutic strategy for promoting fracture healing and preventing nonunion.
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http://dx.doi.org/10.1016/j.omtn.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920808PMC
March 2021

A Novel Instant 3-Dimensional Printing System for Postoperative Fracture Patients: A Comparative Cohort Study.

Med Sci Monit 2021 Jan 1;27:e928240. Epub 2021 Jan 1.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND Traditional plaster (TP) is a widely used auxiliary fixation (AF) approach for postoperative fracture patients. However, patient discomfort and inconvenience to clinicians has limited its application. We introduce a novel instant 3-dimensional printing appliance system (3D-AS) to address such issues. MATERIAL AND METHODS Twenty-seven postoperative fracture patients were divided randomly between a TP group and a 3D-AS group, and analyzed retrospectively. Radiographic images during follow-up were evaluated for fracture healing and fracture reduction quality. The range of motion (ROM) was recorded to assess motor performance. Patient pain was assessed using the Visual Analogue Scale (VAS). Complications were also compared between the 2 groups. RESULTS The patients comprised 17 men and 10 women with ages ranging from 21 to 69 years (mean age: 47.35). All patients completed a follow-up visit (range: 14-19 months, mean: 13.59 months). Although no significant difference was found between general characteristics (P>0.05) and the time of fracture union (P>0.05), significant differences between groups were seen in complications (P<0.05), VAS (P<0.01), patient satisfaction (P<0.05), and ROM for the upper joints (P<0.05). CONCLUSIONS Our study suggests that 3D-AS provides better upper-limb ROM and more comfortable healing for postoperative fracture patients, indicating that it can be recommended for use in such patients.
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http://dx.doi.org/10.12659/MSM.928240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784143PMC
January 2021

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature.

Front Bioeng Biotechnol 2020 23;8:594247. Epub 2020 Oct 23.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteoporosis is a chronic disease requiring long-term, sometimes lifelong, management. With the aging population, the prevalence of osteoporosis is increasing, and with it so is the risk of hip fracture and subsequent poor quality of life and higher mortality. Current therapies for osteoporosis have various significant side effects limiting patient compliance and use. Recent evidence has demonstrated the significant role of exosomes in osteoporosis both and . In this review, we summarize the pathogenesis of senile osteoporosis, highlight the properties and advantages of exosomes, and explore the recent literature on the use of exosomes in osteogenesis regulation. This is a very helpful review as several exosomes-based therapeutics have recently entered clinical trials for non-skeletal applications, such as pancreatic cancer, renal transplantation, and therefore it is urgent for bone researchers to explore whether exosomes can become the next class of orthobiologics for the treatment of osteoporosis.
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http://dx.doi.org/10.3389/fbioe.2020.594247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644826PMC
October 2020

Fibular Neck Osteotomy Approach in Treatment of Posterolateral Tibial Plateau Fractures: A Retrospective Case Series.

Med Sci Monit 2020 Nov 5;26:e927370. Epub 2020 Nov 5.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND The surgical strategies for posterolateral tibial plateau fractures are still inconsistent. Although a number of operative approaches were previously reported for surgical treatment of fractures of the posterolateral column in the tibial plateau, some approaches fail to provide direct visualization of the articular surface and do not allow enough space to access the posterolateral area of the lateral tibial plateau, thereby leading to unsatisfactory reconstruction of the knee and poor articular activity. MATERIAL AND METHODS We retrospectively reviewed records of 21 patients who underwent fibular neck osteotomy approach for posterolateral fractures. Radiographs taken during follow-up were used to evaluate the quality of fracture reduction and lower-limb axis. The Tegner-Lysholm score was used to assess patient functional performance. Complications, including incision infection, osteotomy nonunion, peroneal nerve injury, and fragment displacement, were evaluated. RESULTS We included 12 males and 9 females, with an age range of 27-67 years (mean age, 42.43 years). No intraoperative complications or postoperative complications were found. The mean operative duration was 128.05 min (range: 86-167 min). No patients were lost to clinical or radiographic follow-up. All patients had complete follow-up (range: 13-28 months, mean: 19.57 months). Anatomical fracture reduction was achieved in 14 patients. Radiological limb alignment was restored in all patients. The mean Tegner-Lysholm score was 87.07 (range: 74-95) and the average knee society score (KSS) was 91.67 (range: 86-94) at the final follow-up. CONCLUSIONS In this retrospective study, the results suggest that the fibular neck osteotomy approach is a good choice for treatment of posterolateral tibial plateau fractures.
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http://dx.doi.org/10.12659/MSM.927370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653972PMC
November 2020

A network pharmacology study on analgesic mechanism of Yuanhu-Baizhi herb pair.

BMC Complement Med Ther 2020 Sep 18;20(1):284. Epub 2020 Sep 18.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Millions of people are suffering from chronic pain conditions, such as headache, arthritis, cancer. Apart from western medicines, traditional Chinese medicines are also well accepted for pain management, especially in Asian countries. Yuanhu-Baizhi herb pair (YB) is a typical herb pair applied to the treatment of stomach pain, hypochondriac pain, headache, and dysmenorrhea, due to its effects on analgesia and sedation. This study is to identify potentially active compounds and the underlying mechanisms of YB in the treatment of pain.

Methods: Compounds in YB were collected from 3 online databases and then screened by bioavailability and drug likeness parameters. Swiss target prediction was applied to obtain targets information of the active compounds. Pain-related genes were conducted for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) networks of the genes were constructed using Cytoscape software. In addition, the hub genes were screened using maximal clique centrality (MCC) algorithm.

Results: In total, 31 compounds from Yuanhu were screened out with 35 putative target genes, while 26 compounds in Baizhi with 43 target genes were discovered. Hence, 78 potential target genes of YB were selected for further study. After overlap analysis of the 78 genes of YB and 2408 pain-associated genes, we finally achieved 34 YB-pain target genes, as well as 10 hub genes and 23 core compounds. Go enrichment and KEGG pathway analysis indicated that YB had a strong integration with neuro system, which might significantly contribute to antinociceptive effect.

Conclusion: Our data provide deep understanding of the pharmacological mechanisms of YB in attenuating pain. The discovery shed new light on the development of active compounds of YB for the treatment of pain.
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http://dx.doi.org/10.1186/s12906-020-03078-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501664PMC
September 2020

Low mortality oxidative stress murine chronic wound model.

BMJ Open Diabetes Res Care 2020 09;8(1)

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Introduction: Investigators have struggled to produce a reliable chronic wound model. Recent progress with antioxidant enzyme inhibitors shows promise, but mortality rates are high. We modified the dosage and administration of an antioxidant enzyme inhibitor regimen to reduce mortality while inducing a chronic wound environment.

Research Design And Methods: To chemically induce a chronic wound environment, we applied modified doses of catalase (3-amino-1,2,4-triazole; intraperitoneal 0.5 g/kg) and glutathione peroxidase (mercaptosuccinic acid; topical 300 mg/kg) inhibitors to the dorsal wounds of 11-week-old db/db mice. A cohort of these mice was treated with a collagen-glycosaminoglycan scaffold. Both groups were compared with Diabetic control mice.

Results: This study successfully induced a chronic wound in 11-week-old db/db mice, with no animal deaths. The antioxidant enzyme treated groups showed delayed wound contraction and significantly higher levels of inflammatory tissue, collagen deposition, cellular proliferation and leukocyte infiltration than the Diabetic control group. Angiogenesis was significantly higher in the antioxidant enzyme treated groups, but the vessels were immature and friable. Scaffold engraftment was poor but appeared to promote blood vessel maturation.

Conclusions: Overall, the two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage of wound healing, while the Diabetic control group progressed to the maturation phase and ultimately remodeling. This model may be instrumental for the development of new wound therapeutics.
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http://dx.doi.org/10.1136/bmjdrc-2020-001221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478002PMC
September 2020

Delayed surgery versus nonoperative treatment for hip fractures in post-COVID-19 arena: a retrospective study of 145 patients.

Acta Orthop 2020 Dec 8;91(6):639-643. Epub 2020 Sep 8.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background and purpose - Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods - In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results - Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24-48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation - In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.
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http://dx.doi.org/10.1080/17453674.2020.1816617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023940PMC
December 2020

ANDC: an early warning score to predict mortality risk for patients with Coronavirus Disease 2019.

J Transl Med 2020 08 31;18(1):328. Epub 2020 Aug 31.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.

Background: Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19.

Methods: 301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients.

Results: Age, neutrophil-to-lymphocyte ratio, D-dimer and C-reactive protein obtained on admission were identified as predictors of mortality for COVID-19 patients by LASSO. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively.

Conclusion: The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.
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http://dx.doi.org/10.1186/s12967-020-02505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457219PMC
August 2020

Dispatch of the Medical Force from Wuhan to Beijing: City-wide nucleic acid census.

Br J Surg 2020 10 18;107(11):e476. Epub 2020 Aug 18.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1002/bjs.11935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461292PMC
October 2020
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