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Background: The optimal dose regimen of dexamethasone in total knee arthroplasty (TKA) has not been determined. This study was performed to evaluate the impact of a single preoperative high-dose dexamethasone compared with two perioperative low-dose dexamethasone in TKA. Materials and methods: We prospectively studied three regimens on dexamethasone: no dexamethasone (A), a single preoperative dose of 20-mg dexamethasone (B), and two perioperative doses of 10-mg dexamethasone (C). The primary outcome was postoperative pain level. The incidence of postoperative nausea and vomiting (PONV), use of analgesic and antiemetic rescue, interleukin-6 (IL-6) and C-reactive protein (CRP) levels, range of motion (ROM), and complications were also compared. Results: The dynamic pain scores and CRP and IL-6 levels were significantly lower for Group B compared to Groups A and C on postoperative days 1 and 2 (POD 1 and 2). Such differences were also detected between Groups C and A. Besides, the pain scores at rest were significantly lower in Groups B and C than in Group A on POD 1 and 2. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, and improved ROM than in Group A. No complications occurred in any group. Conclusion: Dexamethasone in TKA provides short-term advantages in analgesic, antiemetic and anti-inflammatory effects. Besides, regarding the effects of pain and inflammatory control on POD 1 and 2, a single preoperative high dose of 20-mg dexamethasone was more effective than two perioperative low doses of 10-mg dexamethasone. Level of evidence: I. [ABSTRACT FROM AUTHOR]

The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, "cell island" microgels (MGs), that is, growth factor‐loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non‐covalently binding platelet‐derived growth factor‐BB (PDGF‐BB) and transforming growth factor‐beta3 (TGF‐β3). The loading efficiency of PDGF‐BB and TGF‐β3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the "cell island" MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF‐BB. Meanwhile, by using hyaluronic acid, the "cell island" MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the "cell island" MGs induce chondrogenic differentiation of the recruited cells via releasing TGF‐β3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed "cell island" MG might serve as a temporary "nest site" to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell‐seeded scaffolds for promoting tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TXA) has proven to be effective in reducing the blood loss associated with total knee arthroplasty (TKA) in patients with osteoarthritis. However, there still exists a paucity of evidence regarding the effectiveness of intravenous TXA in patients with rheumatoid arthritis. The aim of this study was to explore the efficacy and safety of intravenous TXA on blood loss after TKA in Chinese patients with rheumatoid arthritis. Materials and methods: A total of 405 patients with rheumatoid arthritis who had undergone TKA were categorized into two groups based on the protocol of TXA use. TXA group (n = 248): patients received 15 mg/kg TXA prior to operation. Control group (n = 157): patients received no TXA. The outcome measurements such as, total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), transfusion, drainage, the timing of first ambulation, the length of stay (LOS), total hospitalization costs, the results of 12-Item Short Form Survey (SF-12), the incidence of thromboembolic events and other complications were recorded and compared. Results: The mean TBL, IBL, HBL, volume of transfusion and drainage were significantly lower in TXA group than in Control group. The rate of transfusion was significantly lower in TXA group than in Control group. There was a favorable effect in early ambulation for patients in TXA group, compared with patients in Control group. In addition, TXA group had shorter LOS, lower hospitalization costs and higher postoperative SF-12 score than Control group. The incidence of deep venous thrombosis and other complications did not differ between the two groups. Conclusion: TXA can effectively diminish blood loss, reduce transfusion, shorten LOS and decrease hospitalization costs after TKA in Chinese patients with rheumatoid arthritis, without increasing the risk of complications. [ABSTRACT FROM AUTHOR]

Background: Consensus is lacking regarding the dose and timing of tranexamic acid (TXA). The aim of this study was to determine whether multiple-dose intravenous TXA further reduced blood loss and attenuated inflammation after total knee arthroplasty (TKA). Materials and methods: We prospectively studied four regimens on TXA: no TXA (A), before incision, 3, 6, and 12 h later (B), before incision, 3, 6, 12, and 18 h later (C) and before incision, 3, 6, 12, 18, and 24 h later (D). The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss (TBL), intraoperative blood loss (IBL), fibrinolysis parameters [fibrin(-ogen) degradation products, D-dimer], inflammatory factors (C-reactive protein, interleukin-6), visual analog scale (VAS) score, transfusion rate, length of stay (LOS) and complications were also compared. Results: The mean HBL and TBL were significantly lower in Group D than in Groups C, B and A. The level of inflammatory factors and fibrinolysis parameters were significantly lower in Group D than in Groups C, B and A at 24 and 72 h postoperatively. The VAS score on postoperative days 1 and 3 (POD1 and POD3) was significantly lower in Group D than in Groups C, B and A. There was no significant difference in LOS among groups. No patient underwent blood transfusion. No episodes of deep venous thrombosis or pulmonary embolism occurred in all the groups. Conclusion: The repeated doses of TXA up to 24 h can further diminish HBL, provide additional fibrinolysis and inflammation control and ameliorate postoperative pain following TKA. Level of evidence: I [ABSTRACT FROM AUTHOR]

Background: Patients with rheumatoid arthritis (RA) who have undergone total knee arthroplasty are at increased risk of requiring a blood transfusion. This study is designed to compare the effects of preemptive antifibrinolysis of single-dose and repeat-dose tranexamic acid (TXA) in in RA patients undergoing total knee arthroplasty (TKA).Methods/design: The study will be a double-blind randomized controlled trial with two parallel groups of RA patients. Group A will be given 100 ml normal saline twice daily starting from 3 days before the operation, Group B will be given TXA 1.5 g twice daily starting from 3 days before the operation. All patients will be given TXA 1.5 g 30 min before the operation. The primary outcomes will be evaluated with total blood loss and hidden blood loss. Other outcome measurements such as, fibrinolysis parameters, inflammatory factors, visual analogue scale for post-operative pain, analgesia usage, coagulation parameters, transfusion, the length of stay (LOS), total hospitalization costs, the incidence of thromboembolic events and other complications will be recorded and compared. Recruitment is scheduled to begin on 1 August 2020, and the study will continue until 31 May 2021.Discussion: In current literature there is a lack of evidence with regard to the efficacy of TXA in RA patients. The findings of this study, whether positive or negative, will contribute to the formulation of further recommendations on the use of TXA in RA patients undergoing TKA.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000029720 . Registered 14 February 2020. [ABSTRACT FROM AUTHOR]

Due to widespread application of chlorpyrifos for controlling pests in agriculture, the continuous accumulation of chlorpyrifos residue has caused serious environmental pollution.The detection of chlorpyrifos is of great significance for humans and environment because it can arise a series of diseases by inhibiting acetylcholinesterase (AChE) activity. Photoelectrochemical sensing, as an emerging sensing technology, has great potential in the detection of chlorpyrifos. It is urgent that find a suitable photoelectric sensing strategy to effectively monitor chlorpyrifos. Herein, an n-n heterojunction was constructed by uniformly immobilizing n-type 3DBiOI, which had loose porous structure composed of numerous small and thin nanosheets, on the surface of TiO 2 with anatase/rutile (AR-TiO 2) heterophase junction. Under light irradiation, the proposed BiOI/AR-TiO 2 n-n heterojunction exhibited excellent optical absorption characteristics and photoelectrochemical activity. Additionally, the photoelectrochemical sensing platform demonstrated excellent analytical performance in monitoring chlorpyrifos. Under optimized conditions, it showed a wide detection range of 1 pg mL−1- 200 ng mL−1 and a detection limit (S/N = 3) as low as 0.24 pg mL−1, with superior selectivity and stability. The ultra-sensitivity and great specificity for detection of chlorpyrifos can be ascribed to chelation between Bi (Ⅲ) and C=N and P=S bonds in chlorpyrifos, which had been confirmed in this work. Meanwhile, the PEC sensor also had potential application value for monitoring chlorpyrifos in water samples, lettuce and pitaya, which the recoveries of samples ranged from 96.9% to 104.7% with a relative standard deviation (RSD) of 1.11%–5.93%. This sensor provided a novel idea for constructing heterojunctions with high photoelectric conversion efficiency and had a high application prospect for the detection of chlorpyrifos and other structural analogues. [Display omitted] • A novel BiOI/AR-TiO 2 n-n heterojunction was proposed by two-step drop-coated method. • Both AR-TiO 2 and n-type 3DBiOI had superior photoelectric conversion efficiency. • Synergistic effect of AR-TiO 2 and BiOI ensured the excellent performance of sensor. • The chelation of Bi-chlorpyrifos complex gave the sensor excellent selectivity. • This PEC sensor had good recovery results in the analysis of real samples. [ABSTRACT FROM AUTHOR]

References 1 Messier SP, Beavers DP, Queen K. Effect of diet and exercise on knee pain in patients with osteoarthritis and overweight or obesity: a randomized clinical trial. Compared with joints in the upper limb, OA in lower limb joints (eg, hip) is more likely to have an effect on knee pain and function. [Extracted from the article]

Purpose: To assess the efficacy and safety of multiple-dose intravenous tranexamic acid (IV-TXA) on blood loss following total knee arthroplasty (TKA).Methods: One hundred fifty nine patients received one bolus of IV-TXA before skin incision and two boluses three and six hours later (group A), or another bolus nine hours later (group B), or another two boluses nine and 12 hours later (group C). The primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum haemoglobin (Hb) drop. Other outcome measurements such as fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [interleukin-6 (IL-6)], transfusion rate, range of motion (ROM), length of hospital stay (LOH), and complications were also recorded and compared.Results: The mean TBL, HBL and maximum Hb drop in group C (p < 0.001, p < 0.001, p = 0.025) and group B (p = 0.025, p = 0.025, p = 0.044) were lower than those in group A. FDP and D-Dimer in group C was lower than in group A and B on post-operative day one. IL-6 in group A, B and C showed a downward tendency on post-operative days one and three (POD1 and POD3). Moreover, the ROM and LOH were better in group C. No episodes of transfusion or deep venous thrombosis (DVT) were detected in all groups.Conclusions: The 5-dose TXA regimen can further reduce the blood loss, diminish the maximum Hb drop, minimize inflammation, enhance mobility, and shorten LOS following TKA, without increasing the risk of complications. An additional dose could be requisite when fibrinolysis maintains after 5-dose regimen has already been performed.Level Of Evidence: I. [ABSTRACT FROM AUTHOR]

Cell recruitment, injectable, microgels, osteoarthritis, stem cell therapies Stem Cell-Recruiting Injectable Microgels for Repairing Osteoarthritis (Adv. Funct. Keywords: cell recruitment; injectable; microgels; osteoarthritis; stem cell therapies EN cell recruitment injectable microgels osteoarthritis stem cell therapies 1 1 1 12/16/21 20211122 NES 211122 B Injectable Microgels b Inspired by the phenomenon where islands could recruit seabirds for nesting, in article number 2105084, Xiaoji Luo, Wenguo Cui, Wei Huang, and co-workers present an injectable porous microgel generated via microfluidic technology that is non-covalently loaded with PDGF-BB and TGF- 3, forming "cell island" microgels that can serve as a temporary "nest site" to recruit endogenous stem cells and presents a promising therapeutic effect for osteoarthritic cartilage damage. [Extracted from the article]

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly‐2‐acrylamide‐2‐methylpropanesulfonic acid sodium salt‐grafted aminofullerene, is developed to restore the cartilage lubrication system using an “In‐Out” strategy. The “Out” aspect involves reducing friction through a combination of hydration lubrication and ball‐bearing lubrication. Simultaneously, the “In” aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron‐scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro‐robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano‐micron combinations are summarized, and the latest applications of these advanced nano‐micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano‐micron combined HMs are provided. [ABSTRACT FROM AUTHOR]

Organ‐on‐a‐chip, also known as “tissue chip,” is an advanced platform based on microfluidic systems for constructing miniature organ models in vitro. They can replicate the complex physiological and pathological responses of human organs. In recent years, the development of bone and joint‐on‐chip platforms aims to simulate the complex physiological and pathological processes occurring in human bones and joints, including cell–cell interactions, the interplay of various biochemical factors, the effects of mechanical stimuli, and the intricate connections between multiple organs. In the future, bone and joint‐on‐chip platforms will integrate the advantages of multiple disciplines, bringing more possibilities for exploring disease mechanisms, drug screening, and personalized medicine. This review explores the construction and application of Organ‐on‐a‐chip technology in bone and joint disease research, proposes a modular construction concept, and discusses the new opportunities and future challenges in the construction and application of bone and joint‐on‐chip platforms. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-β-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention. • CircRNF169 was dramatically up-regulated in senescent MEFs. • CircRNF169 significantly promoted the replicative senescence of MEFs. • CircRNF169 promoted the replicative senescence of MEFs through acting as a miR-30c-5p sponge. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. Result: We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. Conclusion: The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA. [ABSTRACT FROM AUTHOR]

Energy prosumer participates in the balance of the energy system actively through their production and consumption of energy and will become a major participant in the open energy market increasingly in the future. This paper used the bibliometric method to sort out 1251 literature data related to energy prosumer in the "Web of Science Core Collection" and used the software named CiteSpace to perform statistics and cooccurrence analysis. The research found the following: (a) journals in the field of prosumer have their emphasis on theory, application, policy, and modeling; (b) the United States and European institutions have published the articles most, and the academic influence of Chinese scholars needs to be further improved; (c) the focus of the prosumers' research in the past decade has turned the energy system designing to the market transaction research; (d) P2P, P2G, and prosumer community are three market models that have attracted attention for scholars; besides, self-consumption, market matching, district heating, aggregators, and household energy management systems are also the current research hotspots; (e) digital technologies such as big data, the Internet of Things, and blockchain have a significant impact on the prosumer participating in energy market transactions, which will change the existing energy supply chain model profoundly. In the context of the energy Internet, energy trading platforms, digital ecosystems, cross-border innovation, and other fields will become the hotspots in future research on prosumer. [ABSTRACT FROM AUTHOR]

Background: Psoralea corylifolia is a medicinal leguminous plant that has long been used to treat various diseases. Psoralidin (PSO) is the main extract compound of P. corylifolia and exhibits antibacterial, antitumor, anti-inflammatory, antioxidant, and other pharmacological activities. PSO has demonstrated inhibitory effects in several cancers; however, its inhibitory effect on osteosarcoma has not been reported. This study aimed to evaluate the inhibitory effect of PSO on osteosarcoma and elucidate the underlying molecular mechanisms. Methods: Crystal violet, cell counting kit-8 (CCK8), and 5-Ethynyl-2′-deoxyuridine (EdU) staining assays were used to assess the inhibitory effect of PSO on the proliferation of 143B and MG63 osteosarcoma cells. Wound healing and Transwell assays were conducted to evaluate the effects of PSO on osteosarcoma cell migration and invasion. The cell cycle and apoptosis were analyzed using flow cytometry. To determine the possible molecular mechanisms, RNA-sequencing was performed and protein expression was analyzed by western blotting. The inhibitory effect of PSO on osteosarcoma in vivo was analyzed using a mouse model of orthotopic osteosarcoma and immunohistochemistry. Results: PSO inhibited osteosarcoma cell proliferation in a concentration-dependent manner, inhibited cell migration and invasion, and induced cell-cycle arrest and apoptosis. Mechanistically, PSO treatment significantly inhibited the focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways by downregulating ITGB1 expression in both MG63 and 143B cells. Furthermore, we demonstrated that PSO restrained osteosarcoma growth in vivo. Conclusion: PSO may suppress osteosarcoma via the FAK and PI3K/Akt signaling pathways by downregulating ITGB1 expression. [ABSTRACT FROM AUTHOR]

Metal ions play an important role in promoting tissue regeneration. However, excessive metal ions can also cause certain damage to the human body. In this study, the electrospun short nanofibrous sponges (3D‐NS) functionalized with phosphorus dendrons (3D‐NS@PD) are innovatively constructed, which are capable of dynamically capturing free copper ions at multiple sites to realize the dynamic balance and physiological concentration of copper ions. First, phosphorus dendrons with the long hydrophobic alkyl chain are synthesized by substitution and condensation reactions with hexachlorocyclic triphosphazene as the core. Then, ten pyrrole groups are modified on the surface of phosphorus dendrons, some of which are grafted with copper ions by coordination method, and the remaining pyrrole groups are used to capture free copper ions at multiple sites. Furthermore, phosphorus dendrons modified with pyrrole groups are grafted onto 3D‐NS via π–π conjugation. The captured copper ions can enhance the mechanical properties of the 3D‐NS@PD, which shows stable 3D shape and reversible water absorption after repeated compression by external forces. In vitro and in vivo results show that 3D‐NS@PD effectively promotes bone regeneration by accelerating the formation of neovascularization at the defect sites and regulating the osteogenic differentiation of local bone marrow mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Bleeding patients exhibit different fibrinolytic phenotypes after injury, and the universal use of tranexamic acid (TXA) is doubted. We aimed to evaluate the efficacy of postoperative antifibrinolytic treatment in total hip arthroplasty (THA) patients with different fibrinolytic phenotypes. A retrospective analysis was conducted in 238 patients who underwent THA. Patients were divided into two groups by different fibrinolytic phenotypes (non-fibrinolytic shutdown and fibrinolytic shutdown), determined by the LY30 level on postoperative day 1 (POD1). The two groups were further stratified into four sub-groups based on different postoperative TXA regimens (Group A received no TXA postoperatively, while Group B did). Hidden blood loss (HBL), decline of hemoglobin (ΔHb), D-dimer (D-D), fibrinogen/fibrin degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), and demographics were collected and compared. The clinical baseline data were comparable between the studied groups. In patients who presented non-fibrinolytic shutdown postoperatively, Group B suffered significantly lower HBL and ΔHb than Group A on POD3 and POD5. In patients who presented postoperative fibrinolytic shutdown, Group B failed to benefit from the postoperative administration of TXA when compared to Group A. No difference was found in postoperative levels of D-D, FDP, PT, and APTT. Postoperative antifibrinolytic therapy is beneficial for THA patients who presented non-fibrinolytic shutdown postoperatively, while the efficacy and necessity should be considered with caution in those with fibrinolytic shutdown. LY30 is a promising parameter to distinguish different fibrinolytic phenotypes and guide TXA administration. However, further prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Front Cover: Nano‐micron combined hydrogel microspheres, resembling the Loong Balls in the image, present numerous advantages in therapeutic delivery, tissue repair, and regeneration. They hold immense potential in the realm of minimally invasive biomedical applications, especially in the just‐arrived Loong Year. More details can be found in article number 2300670 by Hong Chen, Wei Huang, Yiting Lei, and co‐workers..By Jiacheng Liu; Chengcheng Du; Hong Chen; Wei Huang and Yiting LeiReported by Author; Author; Author; Author; Author [Extracted from the article]

Background: The empirical use of tranexamic acid (TXA) for bleeding remains controversial because of the distinct fibrinolytic phenotypes observed after injury. This study sought to assess the efficacy of postoperative TXA in patients presenting with different fibrinolytic phenotypes after total knee arthroplasty (TKA). Methods: This retrospective study included 270 patients who underwent primary TKA. The patients were divided into two groups: Group A, received no postoperative TXA, and Group B, received postoperative TXA; they were further categorized into four subgroups based on postoperative fibrinolytic phenotypes (non-fibrinolytic shutdown [NFSD] and fibrinolytic shutdown [FSD]). Fibrinolytic phenotypes were determined using percentage of clot lysis 30 min after maximum strength (LY30) level measured on postoperative day 1 (POD1). Data on perioperative hidden blood loss (HBL), decrease in the hemoglobin level (ΔHb), allogeneic blood transfusion (ABT) rate, fibrin degradation product (FDP) level, D-dimer (D-D) level, prothrombin time (PT), and activated partial thromboplastin time (APTT) as well as clinical baseline data were collected and compared. Results: No differences in baseline clinical data were noted. Among patients presenting with NFSD, those in Group B had significantly lower HBL and ΔHb on POD1 and POD3 than those in Group A. Among patients presenting with FSD, perioperative HBL and ΔHb were similar between the two groups. No differences were observed in perioperative ABT rate, FDP level, D-D level, PT, and APTT. Conclusions: Patients exhibit various fibrinolytic phenotypes after TKA. Postoperative antifibrinolytic strategies may be beneficial for patients presenting with NFSD, but not for those presenting with FSD. The LY30 level may guide targeted TXA administration after TKA. However, well-designed prospective randomized controlled trials are needed to obtain more robust data. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) by promoting Sox9 expression. However, BMP2 also induces chondrocyte hypertrophy and endochondral ossification by upregulating Smad7 expression, which leads to the disruption of chondrogenesis. In addition, Smad7 can be inhibited by Sox9. Therefore, the underlying mechanism is not clear. Currently, an increasing number of studies have shown that microRNAs play a pivotal role in chondrogenic and pathophysiological processes of cartilage. The purpose of this study was to determine which microRNA is increased by Sox9 and targets Smad7, thus assisting BMP2 in maintaining stable chondrogenesis. We found that miR-322-5p meets the requirement through next-generation sequencing (NGS) and bioinformatic analysis. The targeting relationship between miR-322-5p and Smad7 was confirmed by dual-luciferase reporter assays, qPCR, and western blotting (WB). The in vitro study indicated that overexpression of miR-322-5p significantly inhibited Smad7 expression, thus causing increased chondrogenic differentiation and decreased hypertrophic differentiation, while silencing of miR-322-5p led to the opposite results. Flow cytometry (FCM) analysis indicated that overexpression of miR-322-5p significantly decreased the rate of early apoptosis in BMP2-stimulated MSCs, while silencing of miR-322-5p increased the rate. A mouse limb explant assay revealed that the expression of miR-322-5p was negatively correlated with the length of the BMP2-stimulated hypertrophic zone of the growth plate. An in vivo study also confirmed that miR-322-5p assisted BMP2 in chondrogenic differentiation. Taken together, our results suggested that Sox9-increased miR-322-5p expression can promote BMP2-induced chondrogenesis by targeting Smad7, which can be exploited for effective tissue engineering of cartilage. [ABSTRACT FROM AUTHOR]

Aims: To explore the effect of intravenous tranexamic acid (IV-TXA) on inflammation and immune response following primary total knee arthroplasty (TKA). Methods: Primary TKA patients (n = 125) were randomized into the following four groups: group A to receive placebo; group B to receive a single dose of 20 mg kg−1 IV-TXA and 20 mg of intravenous dexamethasone (IV-DXM); group C to receive six doses of IV-TXA (total dosage > 6 g); and group D to receive six doses of IV-TXA combined with three doses of IV-DXM (total dosage = 40 mg). The primary outcomes were C-reactive protein (CRP) and interleukin (IL)-6 levels and the secondary outcomes were complement C3 and C4 and T-cell subset levels, which were measured preoperatively and at 24 h, 48 h, 72 h, and 2 weeks postoperatively. Results: The postoperative peak CRP and IL-6 levels in group C (93.7 ± 22.2 mg L−1, 108.8 ± 41.7 pg mL−1) were lower compared with those in group A (134.7 ± 28.8 mg L−1, P < 0.01; 161.6 ± 64.4 pg mL−1, P < 0.01). Groups B and D exhibited significantly lower CRP and IL-6 levels compared with groups A and C at 24 h, 48 h, and 72 h postoperatively (P < 0.05 for all). In group C, complement C3 and C4 levels were higher compared with those in group A at 48 h (0.967 ± 0.127 g L−1 vs. 0.792 ± 0.100 g L−1, P < 0.01; 0.221 ± 0.046 g L−1 vs. 0.167 ± 0.028 g L−1, P < 0.01) and 72 h (1.050 ± 0.181 g L−1 vs. 0.860 ± 0.126 g L−1, P = 0.01; 0.240 ± 0.052 g L−1 vs. 0.182 ± 0.036 g L−1, P < 0.01) postoperatively and CD3 and CD4 subset levels were higher compared with those in group B at 24 h postoperatively (66.78 ± 9.29% vs. 56.10 ± 12.47%, P < 0.05; 36.69 ± 5.78% vs. 28.39 ± 8.89%, P < 0.05). Conclusion: Six doses of IV-TXA could attenuate the inflammatory effect, modulate the immune response, and reduce immunosuppression caused by DXM in patients after TKA. [ABSTRACT FROM AUTHOR]

Background: In an enhanced recovery after surgery program, not placing a closed suction drain following routine primary total joint arthroplasty (TJA) is becoming more acceptable. However, the influence of drain use on transfusion rate and postoperative length of stay (PLOS) in TJA remains controversial. Therefore, we aimed to compare drain use with no drain in routine primary TJA to determine the differences in transfusion rate and PLOS. Methods: We analyzed the data from 12,992 patients undergoing primary unilateral TJA: 6325 total knee arthroplasties (TKA) and 6667 total hip arthroplasties (THA). Patients were divided into two groups according to whether they received a drain postoperatively following TKA and THA. We extracted information for transfusion and PLOS from patients' electronic health records and analyzed the data by logistic and linear regression analyses. Results: The transfusion rate and PLOS were 15.07% and 7.75 ± 3.61 days, respectively, in the drain group and 6.72% and 6.54 ± 3.32 days, respectively, in the no-drain group following TKA. The transfusion rate and PLOS were 20.53% and 7.00 ± 3.35 days, respectively, in the drain group and 13.57% and 6.07 ± 3.06 days, respectively, in the no-drain group following THA. After adjusting for the following variables: age, gender, body mass index, orthopedic diagnoses, hypertension, type 2 diabetes, coronary heart disease, chronic obstructive pulmonary disease, preoperative hemoglobin, albumin, analgesic use, anesthesia, American Society of Anesthesiologists class, tranexamic acid use, intraoperative bleeding, operative time, and tourniquet use (for TKA), drain use correlated significantly with a higher transfusion rate (risk ratio = 2.812, 95% confidence interval (CI) 2.224–3.554, P < 0.001 for TKA and risk ratio = 1.872, 95% CI 1.588–2.207, P < 0.001 for THA) and a longer PLOS (partial regression coefficient (B) = 1.099, 95% CI 0.879–1.318, P < 0.001, standard regression coefficient (B′) = 0.139 for TKA; B = 0.973, 95% CI 0.695–1.051, P < 0.001, and B′ = 0.115 for THA). Two groups showed no significant difference in wound complications. Conclusions: Our findings indicated that drain use was associated with a higher transfusion rate and a longer PLOS in patients undergoing routine primary TJA. The routine use of postoperative drainage is not recommended in primary unilateral TJA. [ABSTRACT FROM AUTHOR]

Background: Deep vein thrombosis (DVT) is one of the life-threatening complications of total joint arthroplasty (TJA) postoperatively, and its risk factors are still controversial. The aim of this study was to identify the risk factors of DVT after TJA. Study design and methods: A nested case-control study based on a large dataset of 15,326 patients undergoing TJA was performed. Potential risk factors of DVT and demographic information were extracted from the electronic health record. Patients with DVT (73 patients) were treated as study group while non-DVT patients who were matched 1:4 according to the anticoagulant type, were considered as control group (292 patients). These variables of potential risk factors for DVT including age, sex, body mass index (BMI), American Society of Anesthesiologists class, comorbidity, preoperative hemoglobin (HB) level and analgesic use, surgical site (knee or hip) and type, the start time of drug anticoagulation, ambulation time, transfusion, and whether to use tranexamic acid (TXA), drain, human serum albumin, and measures of physical thromboprophylaxis after operation were collected and evaluated by survival analysis and presented as P value and odds ratio with 95% confidence interval. Results: There were 15,326 patients underwent TJA and 73 (0.48%) patients had DVT among them, and the occurrence rates were 0.71% for the patients underwent total knee arthroplasty (TKA) while 0.24% for total hip arthroplasty. The risk factors associated with DVT included TKA (compared with THA), advanced age (> 70 years), drain use, and delayed ambulation (≥ 72 h) postoperatively. Conclusion: The present results suggest that the occurrence rate of DVT on the patients underwent TJA was low (0.48%) relatively. And the risk factors associated with increased risk of DVT included TKA (compared with THA), advanced age, drain use, and delayed ambulation postoperatively. Individualized and more efficient risk stratification protocols of anticoagulation after TJA for Chinese may need to be developed in the future. [ABSTRACT FROM AUTHOR]

Purposes: To explore the efficacy and safety of multiple-dose oral tranexamic acid (TXA) on blood loss following primary total hip arthroplasty (THA).Methods: A total of 152 patients were randomized into three groups to receive 2 g of oral TXA two hours  pre-operatively (group A), or another bolus of 2 g of oral TXA four hours post-operatively (group B), or another three boluses of 2 g of oral TXA four, ten, and 16 hours post-operatively (group C). The primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and transfusion rate. The secondary outcomes were haemoglobin (Hb) and haematocrit (Hct) drop, the level of fibrinolysis parameters (fibrin degradation products, D-dimer), and complications (thrombotic diseases, stroke, cardiac infarction, and infection).Results: The mean TBL and HBL in group C were lower than those in group A (p < 0.001 and p < 0.001) and group B (p = 0.012 and p = 0.029). The Hb drop on post-operative day one (POD1) and POD3 in group C was lower than those in group A (p < 0.001 and p = 0.029) and group B (p < 0.001 and p = 0.004). The difference was similar regarding Hct drop on POD3 (p < 0.001 and p = 0.014). Moreover, fibrin degradation products and D-dimer in group C were lower than in groups A and B on POD1 and POD3 (p < 0.001 and p < 0.001). The incidence of complications such as venous thromboembolism did not differ significantly among the three groups (p > 0.05).Conclusions: Multiple boluses of oral TXA could further reduce blood loss, Hb and Hct drop, and restrain post-operative fibrinolysis in primary THA without increasing the risk of complications.Level Of EvidenceI: Therapeutic study. [ABSTRACT FROM AUTHOR]

Abstract Introduction The aim of this study was to examine whether the administration of multiple boluses of oral or intravenous tranexamic acid (TXA) postoperatively were equivalent at reducing blood loss and the inflammatory and fibrinolytic responses in primary total knee arthroplasty (TKA) without a tourniquet. Materials and methods In this prospective, double-blinded, randomized trial, patients undergoing primary THA were randomized into either an oral or intravenous TXA group. All patients received 1 dose of 20 mg/kg intravenous TXA 5–10 min before skin incision. Patients in the oral TXA group then received 3 doses of 2 g oral TXA at 4, 10, and 16 h postoperatively, while patients in the intravenous TXA group received 3 doses of 1 g intravenous TXA at 6, 12, and 18 h after surgery. Results There was no significant difference in the hemoglobin (Hb) or hematocrit (Hct) drop on postoperative day 1 (14.7 ± 10.5 vs 14.4 ± 9.6 g/L, p = 0.869; 0.042 ± 0.032 vs 0.040 ± 0.028, p = 0.781) and 3 (22.6 ± 10.6 vs 20.5 ± 9.7 g/L, p = 0.300; 0.059 ± 0.031 vs 0.054 ± 0.031, p = 0.332). No patients needed an allogeneic blood transfusion. The mean total blood loss, hidden blood loss, length of hospital stay, the level of inflammatory and fibrinolytic markers on the first and third postoperative days, and the incidence of complications were not significantly different between the two groups (p > 0.05). Conclusion There was no difference in Hb and Hct drop, blood loss, inflammatory and fibrinolytic responses in primary TKA without a tourniquet between those who received multiple boluses of oral or intravenous TXA after surgery in current scheme. Highlights • Multiple boluses of oral TXA and intravenous TXA postoperatively have equivalent effect in reducing Hb and Hct drop, blood loss, inflammatory and fibrinolytic responses in primary TKA without a tourniquet. • Both multiple boluses of oral TXA and intravenous TXA do not increase the risk of complications in the setting of primary TKA, including thromboembolic diseases and wound complications. • Considering the cost-efficient benefits, oral TXA is a superior alternative to intravenous TXA. [ABSTRACT FROM AUTHOR]

Background The appropriate route for administering tranexamic acid in primary total hip (THA) and knee arthroplasty (TKA) remains controversial. The purpose of this meta-analysis was to compare the efficacy and safety of topical or intravenous tranexamic acid. Methods PubMed, EMBASE, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing topical and intravenous tranexamic acid following primary THA or TKA. Primary outcomes were transfusion frequency and maximum drop in hemoglobin. Other parameters included total blood loss (TBL), hidden blood loss, drainage volume, hemoglobin level on postoperative day 1 (POD 1), deep vein thrombosis (DVT), pulmonary embolism (PE), wound complications and other adverse events. Data were analyzed using Rev Man 5.2. Results A total of 18 RCTs involving TKA and 4 RCTs involving THA, corresponding to approximately 2260 patients, were included in the meta-analysis. No significant difference between topical and intravenous tranexamic acid was found in transfusion requirement (RR 1.14, 95%CI 0.87 to 1.50, p = 0.35). The maximum drop in hemoglobin was significantly smaller in the intravenous group than in the topical group (MD 0.33 g/dL, 95%CI 0.07 to 0.58, p = 0.01); similar results were observed for the subset of studies involving THA (MD 0.49 g/dL, 95%CI 0.28 to 0.70, p < 0.001) and the subset involving TKA (MD 0.30 g/dL, 95%CI 0.02 to 0.59, p = 0.04). The topical and intravenous groups did not differ significantly in TBL, drainage volume, hemoglobin level on POD 1, DVT, PE, wound complications or other adverse events. Conclusion The available evidence indicates similar transfusion requirements and safety for topical and intravenous tranexamic acid in THA and TKA. However, intravenous injection seems to be associated with a smaller maximum drop in hemoglobin. [ABSTRACT FROM AUTHOR]

Keywords: 3D short nanofibrous sponges; bone regeneration; copper ions; multisite capturing; phosphorus dendrons EN 3D short nanofibrous sponges bone regeneration copper ions multisite capturing phosphorus dendrons 1 1 1 01/31/23 20230126 NES 230126 B Electrospun Short Nanofibrous Sponges b In article number 2211237, Xiaoji Luo, Wenguo Cui, Wei Huang, and co-workers construct the biomimetic electrospun short nanofibrous sponges functionalized with phosphorus dendrons with the function of loading and multisite capturing free copper ions to realize the integrated repair of vascularization and bone regeneration by promoting osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells. Multisite Captured Copper Ions via Phosphorus Dendrons Functionalized Electrospun Short Nanofibrous Sponges for Bone Regeneration (Adv. Funct. 3D short nanofibrous sponges, bone regeneration, copper ions, multisite capturing, phosphorus dendrons. [Extracted from the article]