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1.
Eur Geriatr Med ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926333

ABSTRACT

PURPOSE: Generalized muscle weakness is the primary characteristic of sarcopenia. Handgrip strength (HGS) is widely employed to detect muscle weakness. However, knee extension strength (KES) declines much earlier and more pronounced than HGS, and there is a stronger correlation between KES and functional performance. Therefore, KES may be a more appropriate proxy for identifying muscle weakness compared to HGS. The purpose of this review was to clarify the KES measurement towards a standardized approach and summarize the cut-off points for KES. METHODS: A literature search was conducted in Web of Science, PubMed, Elsevier, Scopus and Medline databased up to July 10th, 2023. RESULTS: A total of 12 articles were ultimately included in this review, which proposed various cut-off points for KES. Notably, these studies exhibited high heterogeneities, including diverse living settings for participants, KES measurement, methods for KES normalization, methodologies for determining cut-off points and study designs. CONCLUSIONS: No consensus on cut-off points for KES was reached due to the heterogeneities in KES measurement and normalized methods among studies. To enhance the comparability among studies and facilitate the sarcopenia screening framework, a standardized approach for KES measurement and KES normalization are needed. Regarding KES measurement, the hand-held dynamometer-based isometric KES is easy to access and ideally suited for both clinical and community settings, while isokinetic KES, representing the gold standard, is preferred for research settings. Additionally, it is suggested to normalize isometric KES to body weight (BW), while normalizing isokinetic KES to allometrically scaled BW.

2.
Adv Healthc Mater ; 13(15): e2304158, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38319101

ABSTRACT

The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal-phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development.


Subject(s)
Bone Regeneration , Catechin , Extracellular Matrix , Human Umbilical Vein Endothelial Cells , Indoles , Osteogenesis , Tissue Scaffolds , Bone Regeneration/drug effects , Humans , Tissue Scaffolds/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Human Umbilical Vein Endothelial Cells/metabolism , Osteogenesis/drug effects , Indoles/chemistry , Indoles/pharmacology , Animals , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/pharmacology , Polymers/chemistry , Durapatite/chemistry , Durapatite/pharmacology , Strontium/chemistry , Strontium/pharmacology , Nanowires/chemistry , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Cell Differentiation/drug effects , Reactive Oxygen Species/metabolism , Mice , Cell Movement/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
3.
Sci Adv ; 10(1): eadi6799, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38181077

ABSTRACT

Electrical stimulation can effectively accelerate bone healing. However, the substantial size and weight of electrical stimulation devices result in reduced patient benefits and compliance. It remains a challenge to establish a flexible and lightweight implantable microelectronic stimulator for bone regeneration. Here, we use self-powered technology to develop an electric pulse stimulator without circuits and batteries, which removes the problems of weight, volume, and necessary rigid packaging. The fully implantable bone defect electrical stimulation (BD-ES) system combines a hybrid tribo/piezoelectric nanogenerator to provide biphasic electric pulses in response to rehabilitation exercise with a conductive bioactive hydrogel. BD-ES can enhance multiple osteogenesis-related biological processes, including calcium ion import and osteogenic differentiation. In a rat model of critical-sized femoral defects, the bone defect was reversed by electrical stimulation therapy with BD-ES and subsequent bone mineralization, and the femur completely healed within 6 weeks. This work is expected to advance the development of symbiotic electrical stimulation therapy devices without batteries and circuits.


Subject(s)
Bone Regeneration , Osteogenesis , Humans , Animals , Rats , Exercise Therapy , Calcification, Physiologic , Electric Stimulation
4.
J Funct Biomater ; 14(10)2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37888169

ABSTRACT

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications.

5.
Arch Virol ; 168(10): 260, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773227

ABSTRACT

In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of epidemiological research show that EV-A71 infection can cause acute hand, foot, and mouth disease (HFMD) and complications of the nervous system in severe cases, including aseptic pediatric meningoencephalitis, acute flaccid paralysis, and even death. Many studies have demonstrated that EV-A71 infection may trigger a variety of intercellular and intracellular signaling pathways, which are interconnected to form a network that leads to the innate immune response, immune escape, inflammation, and apoptosis in the host. This article aims to provide an overview of the possible mechanisms underlying infection, signaling pathway activation, the immune response, immune evasion, apoptosis, and the inflammatory response caused by EV-A71 infection and an overview of potential therapeutic strategies against EV-A71 infection to better understand the pathogenesis of EV-A71 and to aid in the development of antiviral drugs and vaccines.


Subject(s)
Enterovirus A, Human , Enterovirus Infections , Enterovirus , Hand, Foot and Mouth Disease , Infant , Child , Humans , Child, Preschool , Hand, Foot and Mouth Disease/therapy , Immunity, Innate , Inflammation , Enterovirus A, Human/genetics
6.
Front Surg ; 10: 1100720, 2023.
Article in English | MEDLINE | ID: mdl-36814860

ABSTRACT

Background: Recently, a locking plate (LP) combined with a suture button was applied for distal clavicle Neer type IIb fractures. However, to our knowledge, there is limited information on clinical outcomes surrounding locking plates combined with a suture button in the treatment of Neer type IIb distal clavicle fractures. The aim of this study was to compare the outcomes among three different fixation techniques for the treatment of Neer type IIb distal clavicle fractures. Methods: We performed a retrospective cohort study of 53 patients with Neer type IIb distal clavicle fractures who were treated with a hook plate (HP group, 16 patients), a locking plate alone (LP group, 18 patients), or a locking plate with a suture button (LPSB group, 19 patients) in our hospital between March 2014 and August 2019. The clinical and radiological outcomes were evaluated, including union time, postoperative complications, and function of the shoulder joint. Results: The follow-up period was at least 2 years for all patients. All patients in the LPSB group achieved bone healing at the final follow-up. No significant differences were observed, including age, sex, side, time to surgery, duration of surgery, and mean follow-up period among the three groups (p > 0.05). The union time was shorter in the LPSB group than in the other two groups (p < 0.05). Postoperative complications were lower in the LPSB group than in the other two groups (p < 0.05). The visual analog scale score and Constant-Murley score in the LPSB group were better than those in the other groups at 3 and 6 months postoperatively (p < 0.05). Conclusion: Compared with HP and LP alone, LPSB yields better clinical outcomes and lower complication rates in the treatment of Neer type IIb distal clavicle fractures.

7.
Int Orthop ; 47(1): 233-240, 2023 01.
Article in English | MEDLINE | ID: mdl-36194283

ABSTRACT

PURPOSE: This study aims to evaluate the efficacy of single pararectus approach in patients confirmed with acetabular fracture involving anterior and posterior columns. METHODS: A total of 58 patients confirmed with acetabular fracture involving anterior and posterior columns and treated at our hospital between January 2015 and January 2020 were retrospectively analyzed. A single pararectus approach was applied for all patients. Routine X-rays were performed at follow-up of one, three, six, 12, and 18 months, and three-dimensional CT scans were added at six and 18 months. Fracture reduction quality was assessed using the Matta score system, and functional assessment used the Modified Merle D'Aubigné and Postel score system. Post-operative complications, including fat liquefaction and deep vein thrombosis, were recorded and analyzed. RESULTS: The median operation time was 186 min while the intra-operative blood loss was 421 mL. The rate of good-to-excellent reduction was 94.8%, and the rate of good-to-excellent hip function score reached 93.1%. Seven patients presented with post-operative complications, including three intra-operative small vascular injuries, two peritoneal small perforations, one fat liquefaction, and one deep vein thrombosis. CONCLUSION: Using a single pararectus approach is convenient and effective for treating acetabular fracture involving anterior and posterior columns, especially those involving the quadrilateral area. TRIAL REGISTRATION: ChiCTR, ChiCTR2100054604. Registered 21 December 2022. Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=144783 .


Subject(s)
Fractures, Bone , Hip Fractures , Spinal Fractures , Venous Thrombosis , Humans , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Treatment Outcome , Acetabulum/diagnostic imaging , Acetabulum/surgery , Acetabulum/injuries , Hip Fractures/diagnostic imaging , Hip Fractures/surgery , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
8.
Nat Commun ; 13(1): 7207, 2022 11 23.
Article in English | MEDLINE | ID: mdl-36418292

ABSTRACT

Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS.


Subject(s)
Bone Neoplasms , Osteosarcoma , Young Adult , Adolescent , Child , Humans , Osteosarcoma/genetics , Osteosarcoma/therapy , Genomics/methods , Transcriptome , Platinum , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics
9.
J Funct Biomater ; 13(4)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36278657

ABSTRACT

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient's families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair.

10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(8): 934-939, 2022 Aug 15.
Article in Chinese | MEDLINE | ID: mdl-35979782

ABSTRACT

Objective: To evaluate the effectiveness of TiRobot-assisted surgery by O-arm navigation system for percutaneous minimally invasive treatment of posterior pelvic ring injury. Methods: The clinical data of 76 patients with posterior pelvic ring injury between January 2016 and June 2021 were retrospectively analyzed. Among them, 45 cases were treated with minimally invasive percutaneous sacroiliac screw fixation assisted by TiRobot and O-arm navigation system (study group), 31 cases were treated with minimally invasive percutaneous sacroiliac screw fixation under the guidance of C-arm X-ray machine (control group). There was no significant difference in gender, age, cause of injury, Tile classification, time from injury to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, the times of nail track adjustment, and intraoperative fluoroscopy times were recorded. The quality of fracture reduction was evaluated by Matta score. At last follow-up, Majeed score was used to evaluate the recovery of pelvic function. Results: A total of 72 screws were implanted in the study group, with a median of 1 (1, 2) screws per patient. In the control group, 47 screws were implanted, with a median of 1 (1, 2) screws per patient. There was no significant difference in the number of screws between the two groups ( Z=-0.392, P=0.695). The operation time, intraoperative blood loss, times of nail track adjustment, and intraoperative fluoroscopy times in the study group were significantly less than those in the control group ( P<0.05). All patients were followed up 6-24 months (mean, 14 months). No serious complications was found after operation and during follow-up. Matta score was used to evaluate the quality of fracture reduction at 1 week after operation, and there was no significant difference between the two groups ( Z=-1.135, P=0.256). At last follow-up, there was no significant difference of Majeed score between the two groups ( Z=-1.279, P=0.201). Conclusion: TiRobot-assisted surgery by O-arm navigation system is a reliable surgical method for the treatment of posterior pelvic ring injury, which can reduce the operation time and fluoroscopy times when compared with the traditional operation under the guidance of C-arm X-ray machine. The safety, accuracy, and efficiency of the operation were improved.


Subject(s)
Fractures, Bone , Pelvic Bones , Surgery, Computer-Assisted , Blood Loss, Surgical , Bone Screws , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Humans , Imaging, Three-Dimensional , Minimally Invasive Surgical Procedures/methods , Pelvic Bones/injuries , Pelvic Bones/surgery , Retrospective Studies , Tomography, X-Ray Computed
11.
ACS Appl Mater Interfaces ; 14(32): 36315-36330, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35929013

ABSTRACT

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.


Subject(s)
Biocompatible Materials , Osteogenesis , Alkaline Phosphatase/metabolism , Animals , Biocompatible Materials/pharmacology , Bone Regeneration , Cell Differentiation/physiology , Gelatin , Ions , Methacrylates , Osteogenesis/physiology , Rats , Tissue Scaffolds
12.
Front Surg ; 9: 881852, 2022.
Article in English | MEDLINE | ID: mdl-35586510

ABSTRACT

Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.

13.
Front Bioeng Biotechnol ; 10: 850650, 2022.
Article in English | MEDLINE | ID: mdl-35372318

ABSTRACT

An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo. The results show that the NGCs have good biocompatibility in vitro. Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.

14.
Biomaterials ; 282: 121383, 2022 03.
Article in English | MEDLINE | ID: mdl-35074635

ABSTRACT

Inadequate immune response remains a critical cause of immunotherapy failure in various tumor treatments. Herein, we offer a new approach to achieve a cross-talk between innate and adaptive immune responses based on a new nanoplatform for photothermal therapeutics. The nanoplatform was formed by linking titanium carbide MXene with Mn2+-contained ovalbumin (OVA), where it can trigger efficient mt-DNA presentation and the release of OVA and Mn2+ upon the irradiation of near-infrared laser. More importantly, the released mt-DNA and Mn2+ synergistically activate innate immunity via the cGAS-stimulator of the interferon genes signaling pathway, and the OVA and protein antigens from tumor cells enhance adaptive immunity. Furthermore, in an osteosarcoma model, we observed that the proposed nanoplatform leads to the effective presentation of tumor antigens, which boost the maturation of dendritic cells (DCs) to the hilt and thus improve the infiltration of cytotoxic T lymphocyte in primary and distant tumors. Collectively, our work not only demonstrates a method for constructing a new nanoplatform for photothermal therapeutics but also provides a general strategy for synchronously activating innate and adaptive immunities to promote the maturation of DCs for antimetastasis tumor therapy.


Subject(s)
Bone Neoplasms , Osteosarcoma , Adaptive Immunity , Cell Line, Tumor , DNA , Dendritic Cells , Humans , Immunotherapy/methods , Osteosarcoma/therapy , Ovalbumin
15.
Regen Biomater ; 8(6): rbab068, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34917396

ABSTRACT

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO 4 3 - , when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

16.
J Nanobiotechnology ; 19(1): 275, 2021 Sep 09.
Article in English | MEDLINE | ID: mdl-34503490

ABSTRACT

BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.


Subject(s)
Fibroblast Growth Factor 2/pharmacology , Hydrogels/chemistry , Metal-Organic Frameworks/chemistry , Skin/pathology , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line , Cell Proliferation/drug effects , Compressive Strength , Copper/chemistry , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Hydrogels/pharmacology , Mice , Niacin/chemistry , Rats , Rats, Sprague-Dawley , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology
17.
Int J Oncol ; 59(1)2021 Jul.
Article in English | MEDLINE | ID: mdl-34080667

ABSTRACT

Doxorubicin is one of the most frequently used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to treatment failure. C­X­C motif chemokine receptor 4 (CXCR4) has been demonstrated to regulate OS progression and metastasis. However, whether CXCR4 is also involved in OS chemoresistance and its molecular mechanisms has yet to be fully elucidated. In the present study, CXCR4­mediated autophagy for OS chemotherapy was investigated by western blot analysis, transmission electron microscopy and confocal microscopy. CXCR4 silencing enhanced doxorubicin­induced apoptosis by reducing P­glycoprotein in CXCR4+ LM8 cells, while CXCR4 overexpression promoted OS doxorubicin resistance in CXCR4­ Dunn cells. Furthermore, CXCR4 silencing with or without doxorubicin increased the expression of beclin 1 and light chain 3B, and the number of autophagosomes and autolysosomes, as well as induced autophagic flux activation by suppressing the PI3K/AKT/mTOR signaling pathway. In addition, pretreatment with the autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogation­induced cell death. Finally, the CXCR4 antagonist AMD3100 synergistically reinforced the antitumor effect of doxorubicin in an orthotopic OS mouse model. Taken together, the present study revealed that CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Therefore, targeting the CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.


Subject(s)
Benzylamines/administration & dosage , Bone Neoplasms/drug therapy , Cyclams/administration & dosage , Doxorubicin/administration & dosage , Osteosarcoma/drug therapy , Receptors, CXCR4/metabolism , Signal Transduction/drug effects , Animals , Autophagic Cell Death/drug effects , Benzylamines/pharmacology , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cyclams/pharmacology , Doxorubicin/pharmacology , Drug Synergism , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptors, CXCR4/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism , Xenograft Model Antitumor Assays
18.
J Orthop Surg Res ; 16(1): 315, 2021 May 17.
Article in English | MEDLINE | ID: mdl-34001151

ABSTRACT

BACKGROUND: Preoperative posterior tilt is a risk factor for fixation failure in femoral neck fractures. This study aimed to evaluate the configuration of anterior positioning screw in proximal femoral plating in the treatment of retroverted femoral neck fractures in terms of resisting posterior tilt. METHODS: We retrospectively analyzed patients with retroverted femoral neck fractures who were fixed by proximal femoral plating from January 2014 to August 2019. All patients were divided into two groups according to screw configuration: anterior long-threaded screw (ALTS, n = 36) and normally short-threaded screws (NTS, n = 46). Baseline characteristics were reviewed and radiological and clinical outcomes were analyzed. Logistic regression analysis was used to identify risk factors for developing posterior tilt. RESULTS: Age, gender, Garden classification, posterior comminution, and reduction quality showed no significant difference between the groups. Increased posterior tilt was lower in the ALTS group (3.2°, 2.1-4.3°) than that in the NTS group (5.3°, 4.2-8.3°) (p < 0.001), and the percentage of people with > 5° of posterior tilt was also lower in the ALTS group (5, 13.9% vs. 24, 52.2%; p < 0.001). Femoral neck shortening (FNS) was lower in the ALTS group (3.1 (2.1-4.7) mm vs. 4.3 (3.1-6.3) mm, p = 0.003), though not statistically significant when using 5 mm as the cut-off value. Harris Hip Score in the ALTS group was higher than that in the NTS group (87.0, 84.0-90.0 vs. 82.0, 76.0-84.5; p < 0.001). Postoperative complications including delayed union, nonunion, and avascular necrosis were comparable between the groups. Multivariable analysis identified posterior comminution (OR 15.9, 95% CI 3.6-70.3, p < 0.001), suboptimal reduction quality (OR 12.0, 95% CI 2.6-56.1, p = 0.002), and NTS configuration (reference: ALTS configuration) (OR 21.9, 95% CI 4.1-116.4, p < 0.001) as risk factors for developing posterior tilt. CONCLUSIONS: Configuration of anterior positioning screw in proximal femoral plating provides better resistance against posterior tilt in the fixation of retroverted femoral neck fractures. Also, posterior comminution, suboptimal reduction, and NTS configuration (reference: ALTS) are risk factors for developing posterior tilt. TRIAL REGISTRATION: The trial registration number was ChiCTR2000039482 .


Subject(s)
Bone Plates , Bone Screws , Femoral Neck Fractures/surgery , Fracture Fixation, Internal/methods , Postoperative Complications/etiology , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies
20.
Injury ; 52(6): 1614-1620, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33461771

ABSTRACT

OBJECTIVES: Dual plate fixation has been reported to be effective in the treatment of comminuted distal femur fractures (DFFs). However, optimized use of the medial plate and screws is less studied. This study aimed to evaluate the effect of a hybrid configuration of the medial plate in dual plate fixation of comminuted DFFs in promoting fracture healing. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with comminuted DFFs (AO/OTA 33-A3/33-C2/33-C3) from January 2015 to March 2020, who were either fixed with lateral locked plating augmented with hybrid locked medial plating (LP-HLMP, n = 32) or lateral locked plating (LLP, n = 30) alone. Specifically, compression screws were applied in the middle of the medial plate and flanked by locking ones at both ends. Baseline characteristics, radiological and clinical outcomes were reviewed and analyzed. Multivariate logistic regression analysis was used to identify predictive factors for early fracture healing, and risk factors for delayed union/nonunion. RESULTS: Demographics including age, gender, smoking, diabetes, and injury mechanism were comparable between the two groups. Reduction quality was better in the LP-HLMP group (p < 0.001). Although the LP-HLMP group experienced longer duration of surgery (125 min vs. 100 min, p < 0.001), sign of healing at 3 months was more obvious in this group (75%, 24/32 vs. 30%, 9/30; p < 0.001). The LP-HLMP group also presented with higher union rate (93.8%, 30/32 vs. 56.7%, 17/30; p = 0.001) and lower reoperation rate (0%, 0/32 vs. 13.3%, 4/30; p = 0.049). Kolment score showed no statistical significance between the two groups. Multivariate analysis revealed that younger age (< 60 years) (OR 5.99, 95%CI 1.16 - 31.03; p = 0.001) and LP-HLMP fixation (OR 45.90, 95% CI 4.78 - 440.56; p = 0.001) predict early healing; while smoking (OR 17.80, 95% CI 2.41 - 131.49; p = 0.01) and fracture translation (OR 3.49, 95% CI 1.46 - 8.32; p = 0.01) were identified as risk factors for delayed union/nonunion. CONCLUSION: Hybrid locked medial plating in this study favors the healing of comminuted DFFs and reduces reoperation. Additionally, smoking and suboptimal reduction (translation) predict delayed union/nonunion.


Subject(s)
Femoral Fractures , Fractures, Comminuted , Bone Plates , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Femur , Fracture Fixation, Internal , Fracture Healing , Fractures, Comminuted/diagnostic imaging , Fractures, Comminuted/surgery , Humans , Middle Aged , Retrospective Studies , Treatment Outcome
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