Publications by authors named "Guohui Liu"

163 Publications

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

Blood Purif 2022 Aug 11:1-11. Epub 2022 Aug 11.

Department of Nephrology, Shanghai Sixth People's Hospital, Shanghai, China.

Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients.

Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score.

Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively.

Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.
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http://dx.doi.org/10.1159/000525225DOI Listing
August 2022

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

Bioinspired Nanovesicles Convert the Skeletal Endothelium-Associated Secretory Phenotype to Treat Osteoporosis.

ACS Nano 2022 Jul 8. Epub 2022 Jul 8.

Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named Shanghai First People's Hospital), Shanghai 200080, China.

Recently, bone marrow endothelial cells (BMECs) were found to play an important role in regulating bone homeostasis. However, few studies utilized BMECs to treat bone metabolic diseases including osteoporosis. Here, we reported bioinspired nanovesicles (BNVs) prepared from human induced pluripotent stem cells-derived endothelial cells under hypoxia culture through an extrusion approach. Abundant membrane C-X-C motif chemokine receptor 4 conferred these BNVs bone-targeting ability and the endothelial homology facilitated the BMEC tropism. Due to their unique endogenous miRNA cargos, these BNVs re-educated BMECs to secret cytokines favoring osteogenesis and anti-inflammation. Owing to the conversion of secretory phenotype, the osteogenic differentiation of bone mesenchymal stem cells was facilitated, and the M1-macrophage-dominant pro-inflammatory microenvironment was ameliorated in osteoporotic bones. Taken together, this study proposed BMEC-targeting nanovesicles treating osteoporosis converting the skeletal endothelium-associated secretory phenotype.
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http://dx.doi.org/10.1021/acsnano.2c03781DOI Listing
July 2022

MiR-21 regulating PVT1/PTEN/IL-17 axis towards the treatment of infectious diabetic wound healing by modified GO-derived biomaterial in mouse models.

J Nanobiotechnology 2022 Jun 28;20(1):309. Epub 2022 Jun 28.

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

Background: Diabetic foot ulcer (DFU), persistent hyperglycemia and inflammation, together with impaired nutrient and oxygen deficiency, can present abnormal angiogenesis following tissue injury such that these tissues fail to heal properly. It is critical to design a new treatment method for DFU patients with a distinct biomechanism that is more effective than current treatment regimens.

Method: Graphene oxide (GO) was combined with a biocompatible polymer as a kind of modified GO-based hydrogel. The characterization of our biomaterial was measured in vitro. The repair efficiency of the biomaterial was evaluated in the mouse full-skin defect models. The key axis related to diabetic wound (DW) was identified and investigated using bioinformatics analyses and practical experiments.

Result: In the study, we found that our modified GO-based wound dressing material is a promising option for diabetic wound. Secondly, our biomaterial could enhance the secretion of small EVs (sEVs) with more miR-21 by adipose-derived mesenchymal stem cells (AD-MSCs). Thirdly, the PVT1/PTEN/IL-17 axis was found to be decreased to promote DFU wound healing by modifying miR-21 with the discovery of PVT1 as a critical LncRNA by bioinformatics analysis and tests.

Conclusion: These findings could aid in the development of clinical care strategies for DFU wounds.
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http://dx.doi.org/10.1186/s12951-022-01516-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238182PMC
June 2022

A review on pathology, mechanism, and therapy for cerebellum and tremor in Parkinson's disease.

NPJ Parkinsons Dis 2022 Jun 24;8(1):82. Epub 2022 Jun 24.

Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Tremor is one of the core symptoms of Parkinson's disease (PD), but its mechanism is poorly understood. The cerebellum is a growing focus in PD-related researches and is reported to play an important role in tremor in PD. The cerebellum may participate in the modulation of tremor amplitude via cerebello-thalamo-cortical circuits. The cerebellar excitatory projections to the ventral intermediate nucleus of the thalamus may be enhanced due to PD-related changes, including dopaminergic/non-dopaminergic system abnormality, white matter damage, and deep nuclei impairment, which may contribute to dysregulation and resistance to levodopa of tremor. This review summarized the pathological, structural, and functional changes of the cerebellum in PD and discussed the role of the cerebellum in PD-related tremor, aiming to provide an overview of the cerebellum-related mechanism of tremor in PD.
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http://dx.doi.org/10.1038/s41531-022-00347-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232614PMC
June 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

Editorial: Tissue Stem Cells During Trauma: From Basic Biology to Translational Medicine.

Front Cell Dev Biol 2022 26;10:914582. Epub 2022 May 26.

Institute of Life Science, College of Medicine, Swansea University, Swansea, United Kingdom.

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http://dx.doi.org/10.3389/fcell.2022.914582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178558PMC
May 2022

Bias and Type I error Control in Correcting Treatment Effect for Treatment Switching Using Marginal Structural Models in Phase III Oncology Trials.

J Biopharm Stat 2022 Jun 3:1-18. Epub 2022 Jun 3.

Statistical and Quantitative Science Department, Takeda Pharmaceutical Company, Ltd. Cambridge, Massachusetts, USA.

This research focuses on the bias and type I error control issues when the marginal structural models (MSMs) are applied to evaluate the causal survival benefits of active intervention versus control in randomized clinical trials (RCTs) with treatment switching after disease progression. When MSMs are applied in the RCT setting, the question of interest, model specifications, strategies for type I error control, bias reduction, etc. differ somewhat from those for observational studies. This manuscript discusses the approaches used to accommodate these differences. Through Monte Carlo simulations and a case study, our research demonstrates that, with sufficient attention paid to issues applicable to RCTs in particular, MSMs may perform better than the inverse probability of censoring weighting (IPCW) method in analyzing the survival endpoint in RCTs with treatment switching because more information is used by the MSM.
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http://dx.doi.org/10.1080/10543406.2022.2058524DOI Listing
June 2022

IFC-305 attenuates renal ischemia-reperfusion injury by promoting the production of hydrogen sulfide (HS) via suppressing the promoter methylation of cystathionine γ-lyase (CSE).

Bioengineered 2022 05;13(5):12045-12054

Nephrology Department, Dongguan People's Hospital Affiliated to Southern Medical University, Dongguan, China.

Renal ischemia-reperfusion (I/R) injury is characterized by elevated expression of homocysteine and decreased production of hydrogen sulfide (HS). Cystathionine γ-lyase (CSE) is a key factor in the onset of renal I/R injury, while IFC-305 can regulate the expression of CSE via epigenetic modification. Animal and cellular models of I/R were established in this work, followed by H&E staining to evaluate the extent of renal tissue injury under distinct conditions. Several methods, including ELISA, qPCR and Western blot, were used to analyze the levels of creatinine, CSE and HS in various I/R models. Bisulfite sequencing PCR was used to evaluate the level of DNA methylation. The severity of the renal injury was significantly elevated in I/R rats and alleviated by the IFC-305 treatment. The level of Hcy was increased in the renal tissue and peripheral blood of I/R rats, while the IFC-305 treatment inhibited the expression of homocysteine (Hcy). Mechanistically, the DNA methylation in the CSE promoter was dramatically enhanced in I/R rats and cells, while the IFC-305 treatment reduced the level of DNA methylation in the CSE promoter. Moreover, the IFC-305 increased the concentration of HS, which was reduced in I/R rats and cells. Finally, I/R rats and cells showed aberrantly high levels of MDA and superoxide, while the IFC-305 treatment reduced the levels of malondialdehyde (MDA) and superoxide. IFC-305, an adenosine derivative, promoted the production of HS and attenuated renal injury in cellular and animal models of renal I/R by modifying the methylation status of the CSE promoter.
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http://dx.doi.org/10.1080/21655979.2022.2062105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275864PMC
May 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

Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Accelerate Diabetic Wound Healing Ameliorating Oxidative Stress and Promoting Angiogenesis.

Front Bioeng Biotechnol 2022 31;10:829868. Epub 2022 Jan 31.

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

Diabetic wounds remain a great challenge for clinicians due to the multiple bacterial infections and oxidative damage. Exosomes, as an appealing nanodrug delivery system, have been widely applied in the treatment of diabetic wounds. Endovascular cells are important component cells of the vascular wall. Herein, we investigated the effects of HUCMSCs and HUC-Exos (exosomes secreted by HUCMSCs) on diabetic wound healing. In this study, HUVECs were coincubated with HUCMSCs, and HUC-Exos were utilized for and experiments to verify their roles in the regulation of diabetic wound healing. Our results demonstrated that HUCMSCs have the ability to regulate oxidative stress injuries of endothelial cells through exosomes and accelerate diabetic cutaneous wound healing . The present study suggests that HUC-Exos accelerate diabetic cutaneous wound healing, providing a promising therapeutic strategy for chronic diabetic wound repair.
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http://dx.doi.org/10.3389/fbioe.2022.829868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841645PMC
January 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

Early application of extracorporeal membrane oxygenation for myocarditis with shock: a case report.

J Int Med Res 2021 Nov;49(11):3000605211058875

Jilin Provincial Cardiovascular Research Institute, Department of Cardiology in the Third Hospital of Jilin University, Jilin, China.

The current therapy for myocarditis is immunosuppressive therapy. However, in rare cases in which patients do not respond to intervention, their condition can rapidly deteriorate to myocarditis with shock, which is characterized by extensive and diffuse lymphocyte infiltration in the myocardium. Most cases of myocarditis are caused by virus-mediated damage of cardiomyocytes, and its clinical manifestations are ventricular arrhythmia and hemodynamic disturbances. Extracorporeal membrane oxygenation is an effective intervention, which regulates hemodynamic stability and avoids systemic hypoperfusion. This intervention has been used to sustain hemodynamic stability in patients with myocarditis and shock. We report here early application of extracorporeal membrane oxygenation for successful treatment of a patient with myocarditis and shock.
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http://dx.doi.org/10.1177/03000605211058875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647248PMC
November 2021

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

Vanadium Induces Oxidative Stress and Mitochondrial Quality Control Disorder in the Heart of Ducks.

Front Vet Sci 2021 26;8:756534. Epub 2021 Oct 26.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Vanadium (V) is an ultra-trace element presenting in humans and animals, but excessive V can cause toxic effects. Mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial functions, but the relationship between V toxicity and MQC is unclear. To investigate the effects of excessive V on oxidative stress and MQC in duck hearts, 72 ducks were randomly divided into two groups, including the control group and the V group (30 mg of V/kg dry matter). The cardiac tissues were collected for the histomorphology observation and oxidative stress status evaluation at 22 and 44 days. In addition, the mRNA and protein levels of MQC-related factors were also analyzed. The results showed that excessive V could trigger vacuolar degeneration, granular degeneration, as well as mitochondrial vacuolization and swelling in myocardial cells. In addition, CAT activity was elevated in two time points, while T-SOD activity was increased in 22 days but decreased in 44 days after V treatment. Meanwhile, excessive V intake could also increase the number of Drp1 puncta, the mRNA levels of mitochondrial fission-related factors (Drp1and MFF), and protein (MFF) level, but decrease the number of Parkin puncta and the mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM), mitochondrial fusion (OPA1, Mfn1, and Mfn2), and mitophagy (Parkin, PINK1, P62, and LC3B) related mRNA levels and protein (PGC-1α, Mfn1, Mfn2, PINK1) levels. Collectively, our results suggested that excessive V could induce oxidative stress and MQC disorder in the heart of ducks.
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http://dx.doi.org/10.3389/fvets.2021.756534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577801PMC
October 2021

Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression-Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress.

Oxid Med Cell Longev 2021 25;2021:2310025. Epub 2021 Oct 25.

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

Oxidative stress is relevant in compression-induced nucleus pulposus (NP) cell apoptosis and intervertebral disc (IVD) degeneration. Exosomes derived from bone mesenchymal stem cells (BMSCs-Exos) are key secretory products of MSCs, with important roles in tissue regeneration. This research is aimed at studying the protective impact of BMSCs-Exos on NP cell apoptosis caused by compression and investigating the underlying mechanisms. Our results indicated that we isolated BMSCs successfully. Exosomes were isolated from the BMSCs and found to alleviate the inhibitory effect that compression has on proliferation and viability in NP cells, decreasing the toxic effects of compression-induced NP cells. AnnexinV/PI double staining and TUNEL assays indicated that the BMSCs-Exos reduced compression-induced apoptosis. In addition, our research found that BMSCs-Exos suppressed compression-mediated NP oxidative stress by detecting the ROS and malondialdehyde level. Furthermore, BMSCs-Exos increased the mitochondrial membrane potential and alleviated compression-induced mitochondrial damage. These results indicate that BMSCs-Exos alleviate compression-mediated NP apoptosis by suppressing oxidative stress, which may provide a promising cell-free therapy for treating IVD degeneration.
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http://dx.doi.org/10.1155/2021/2310025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560283PMC
February 2022

Changes in the Quality of Life, Psychological Status, Medication Compliance, and Prognosis of Patients with Acute Myocardial Infarction after PCI by Applying PDCA Cycle Management Model.

Evid Based Complement Alternat Med 2021 19;2021:7318653. Epub 2021 Oct 19.

Department of Cardiology, Renmin Hospital of Hubei University of Medicine, Shiyan, Hubei 442000, China.

Objective: To discuss the changes in the quality of life, psychological status, medication compliance, and prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by applying plan-do-check-action (PDCA) cycle management model.

Methods: A total of 125 patients with AMI who underwent PCI in our hospital from June 2018 to June 2020 were selected and divided into control group ( = 62) and research group ( = 63) by the random number method. The conventional nursing measures were used in the control group, and the PDCA cycle management model on the basis of the control group was used in the research group. The changes in the quality of life, psychological status, medication compliance, and prognosis were observed.

Results: After intervention, the Generic Quality of Life Inventory-74 scores and the self-made medication compliance questionnaire score of the research group were higher than the control group ( < 0.05). After intervention, the self-rating anxiety scale score and self-rating depression scale score of the research group were lower than those of the control group ( < 0.05). The total incidence of adverse events in the research group (7.94%) was lower than that in the control group (20.97%) ( < 0.05).

Conclusion: After the application of PDCA cycle management model, the quality of life, psychological status, medication compliance, and prognosis of AMI patients who underwent PCI were improved.
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http://dx.doi.org/10.1155/2021/7318653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548087PMC
October 2021

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

Study on the chemical changes of Quercus acuttisima by Ganoderma lucidum cultivation after different years by FTIR analysis.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Feb 28;266:120443. Epub 2021 Sep 28.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address:

The popularmedicinal mushroomGanodermalucidum was often cultivated by the natural-log. Generally the short log after cultivation were discarded and became pollutant. Rapid and less destructive method of analysis technical by Fourier Transform Infrared (FTIR) and Two-dimension Infrared (2DIR) correlation spectroscopy were selected to determine the composition changes of the logs after G.lucidum cultivation after first year to fifth year. The FTIR accumulated spectra formed without processed baseline showed the samples relied upon a sequenced increase of higher level than spectrum control Q (Q = Quercus acuttisima) from L + Q-5 (L = Lingzhi), L + Q-3, L + Q-1 to L + Q-2. The spectrum L + Q-4 has the optimum highest peak at box B, C and E from this lumped spectral view. The split spectra pinpointed on the fingerprint region of a sample begins from peak 1737 cm. ascribed C = O stretching vibration on acetyl and carboxyl hemicellulose group bonding gradually faded from L + Q-1 to L + Q-4 but appeared again on L + Q-5, possibly due to the degradation of hemicellulose. The absorption of peak around 1626 cm,1318 cm and 781 cm could be the characteristic absorption peak of calcium oxalate monohydrate. The correlation table indicated, most of the original structure of the building block of the wooden part was deteriorated and marked the lowest correlation value of the 4th year sample with control Q. The sudden changing pattern of 2nd derivative spectrum L + Q-3 to more flatten pattern spectrum L + Q-4 ascribed the changing contents of cellulose and hemicellulose included the lignin within one year during the G. lucidum cultivation. The 2DIR spectrum of the raw material sample precisely showed that the active site with red color was clustered with the area around 1800-1700 cm, 1450-800 cm and 750-400 cm. In between, the range 1450-800 cm was the most active cluster. Each of the sample showed the different sequence of autopeak comparison. This study has examined the impact of G. lucidum on the degradation of Q. acuttisima in term of their ecosystem life chain. The components of healthy Q. acuttisima wood including lignin, cellulose, hemicellulose and calcium oxalate monohydrate underwent changes after different years of G. lucidum cultivation.
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http://dx.doi.org/10.1016/j.saa.2021.120443DOI Listing
February 2022

Effects of Subchronic Copper Poisoning on Cecal Histology and Its Microflora in Chickens.

Front Microbiol 2021 8;12:739577. Epub 2021 Sep 8.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, China.

Copper (Cu) is an important trace element with a two-sided effect on the growth performance of animals, which depends on the timing and dosage of Cu addition, etc. The purpose of this study was to determine the effects of oral copper sulfate (CuSO, 350 ppm) on growth performance, cecal morphology, and its microflora of chickens ( = 60) after 30, 60, and 90 days. The results showed that after 90 days of copper exposure, the chickens lost weight, the cecum mucosa was detached, and vacuolation and inflammatory infiltration occurred at the base of the lamina propria. In addition, using the 16S rDNA sequencing method, we observed that copper exposure changed the richness and diversity of intestinal microorganisms. At the phylum level, and both significantly increased, while significantly decreased in the Cu group compared with control check (CK) group. At the genus level, the relative abundance of decreased significantly, while , and increased significantly after copper exposure, and the change in microflora was most significant at 90 days. Moreover, the relevance of genus-level bacteria was altered. PICRUST analysis revealed potential metabolic changes associated with copper exposure, such as infection and metabolic disorders of nutrients. To sum up, these data show that subchronic copper exposure not only affects the growth and development of chickens but also causes the imbalance of intestinal microflora, which may further induce metabolic disorders in chickens.
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http://dx.doi.org/10.3389/fmicb.2021.739577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456085PMC
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
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