Bone and Joint-on-Chip Platforms: Construction Strategies and Applications.

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.

Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis.

Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.

Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery.

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment.

Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis.

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.

Template-Free Synthesis and Multifunctional Application of Foam HKUST-1.

Hierarchically porous metal-organic frameworks (HP-MOFs) have attracted a lot of attention in recent years because their hierarchical pores have critical importance in strengthening their performance, including guest diffusion kinetics, catalytic activity, and selectivity, especially with reference to large molecules. However, the preparation method for simple, controllable, and stable HP-MOFs at a micro-/meso-/macroscopic scale is still lacking. Herein, we showed several forms of HKUST-1 (HKUST = Hong Kong University of Science and Technology) by simply changing the copper source and solvent type, including original micron HKUST-1 (O-HKUST-1), half-foam HKUST-1 (HF-HKUST-1), and fully foam HKUST-1 (F-HKUST-1). Compared to O-HKUST-1, HF-HKUST-1 and F-HKUST-1 possessed an apparent hierarchically porous structure due to the high fusion of HKUST-1 nanocrystals. Especially in F-HKUST-1, all of the HKUST-1 nanocrystals were tightly integrated into each other, which formed a holistic hollow foam structure. Hence, F-HKUST-1 exhibited the highest adsorption capacity toward large molecules, including proteases, phosphotungstic acid, and organic dyes. Meanwhile, F-HKUST-1 presented the highest photocatalytic degradation capability for rhodamine B. Furthermore, F-HKUST-1, loaded with phosphotungstic acid (F-HKUST-1@PTA), which was used as a catalyst, indicated a catalytic capacity comparable to that of a homogeneous catalyst (pure phosphotungstic acid).

Migration Behavior of Inclusions at the Solidification Front in Oxide Metallurgy.

Distribution of inclusions plays an essential role in inducing intracrystalline ferrite, and the migration behavior of inclusions during solidification has a significant influence on their distribution. The solidification process of DH36 (ASTMA36) steel and the migration behavior of inclusions at the solidification front were observed in situ using high-temperature laser confocal microscopy. The annexation, rejection, and drift behavior of inclusions in the solid-liquid two-phase region were analyzed, providing a theoretical basis for regulating the distribution of inclusions. Analysis of inclusion trajectories showed that the velocity of inclusions decreases significantly as they near the solidification front. Further study of the force on inclusions at the solidification frontier shows three situations: attraction, repulsion, and no influence. Additionally, a pulsed magnetic field was applied during the solidification process. The original dendritic growth mode changed to that of equiaxed crystals. The compelling attraction distance for inclusion particles with a diameter of 6 µm at the solidification interface front increased from 46 µm to 89 µm, i.e., the effective length for the solidification front engulfing inclusions can be increased by controlling the flow of molten steel.

Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

Bone defects, especially large ones, are clinically difficult to treat. The development of new bone repair materials exhibits broad application prospects in the clinical treatment of trauma. Bioceramics are considered to be one of the most promising biomaterials owing to their good biocompatibility and bone conductivity. In this study, a self-curing bone repair material having a controlled degradation rate was prepared by mixing calcium citrate, calcium hydrogen phosphate, and semi-hydrated calcium sulfate in varying proportions, and its properties were comprehensively evaluated. In vitro cell experiments and RNA sequencing showed that the composite cement activated PI3K/Akt and MAPK/Erk signaling pathways to promote osteogenesis by promoting the proliferation and osteoblastic differentiation of mesenchymal stem cells. In a rat model with femoral condyle defects, the composite bone cement showed excellent bone repair effect and promoted bone regeneration. The injectable properties of the composite cement further improved its practical applicability, and it can be applied in bone repair, especially in the repair of irregular bone defects, to achieve superior healing.

Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.

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.

The natural product salicin alleviates osteoarthritis progression by binding to IRE1α and inhibiting endoplasmic reticulum stress through the IRE1α-IκBα-p65 signaling pathway.

Despite the high prevalence of osteoarthritis (OA) in older populations, disease-modifying OA drugs (DMOADs) are still lacking. This study was performed to investigate the effects and mechanisms of the small molecular drug salicin (SA) on OA progression. Primary rat chondrocytes were stimulated with TNF-α and treated with or without SA. Inflammatory factors, cartilage matrix degeneration markers, and cell proliferation and apoptosis markers were detected at the mRNA and protein levels. Cell proliferation and apoptosis were evaluated by EdU assays or flow cytometric analysis. RNA sequencing, molecular docking and drug affinity-responsive target stability analyses were used to clarify the mechanisms. The rat OA model was used to evaluate the effect of intra-articular injection of SA on OA progression. We found that SA rescued TNF-α-induced degeneration of the cartilage matrix, inhibition of chondrocyte proliferation, and promotion of chondrocyte apoptosis. Mechanistically, SA directly binds to IRE1α and occupies the IRE1α phosphorylation site, preventing IRE1α phosphorylation and regulating IRE1α-mediated endoplasmic reticulum (ER) stress by IRE1α-IκBα-p65 signaling. Finally, intra-articular injection of SA-loaded lactic-co-glycolic acid (PLGA) ameliorated OA progression by inhibiting IRE1α-mediated ER stress in the OA model. In conclusion, SA alleviates OA by directly binding to the ER stress regulator IRE1α and inhibits IRE1α-mediated ER stress via IRE1α-IκBα-p65 signaling. Topical use of the small molecular drug SA shows potential to modify OA progression.

High Fluoride Ingestion Impairs Bone Fracture Healing by Attenuating M2 Macrophage Differentiation.

Fluorosis is still endemic in at least 25 countries around the world. In this study, we investigated the effect of high fluoride intake on fracture healing. Our in vitro experiments found that fluoride inhibited the osteogenic and angiogenic differentiation of MSCs in a dose-dependent manner. By constructing a bone fracture model, we found that high fluoride intake influences bone fracture by attenuating endochondral ossification and angiogenesis. In the mechanism, we clarified that high fluoride inhibits M2 differentiation rather than M1 differentiation in the fracture area, which may contribute to the delayed healing of the fracture. These findings provide an essential reference for the clinical treatment of bone fracture patients with a history of high fluoride intake or skeletal fluorosis patients.

Sox9-Increased miR-322-5p Facilitates BMP2-Induced Chondrogenic Differentiation by Targeting Smad7 in Mesenchymal Stem Cells.

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.

Effect of Molybdenum on the Impact Toughness of Heat-Affected Zone in High-Strength Low-Alloy Steel.

The microstructure, precipitates, and austenite grain in high-strength low-alloy steel were characterized by optical microscope, transmission electron microscope, and laser scanning confocal microscopy to investigate the effect of Mo on the toughness of steel. The microstructure was refined and the toughness was enhanced after the addition of 0.07% Mo in steel. The addition of Mo can suppress the Widmanstätten ferrite (WF) formation and promote the transformation of acicular ferrite (AF), leading to the fine transformed products in the heat-affected zone (HAZ). The chemical composition of precipitates changed from Nb(C, N) to (Nb, Mo)(C, N) because of the addition of Mo. The calculated lattice misfit between Nb(C, N) and ferrite was approximately 11.39%, while it was reduced to 5.40% for (Nb, Mo)(C, N), which significantly affected the size and number density of precipitates. A detailed analysis of the precipitates focusing on the chemical composition, size, and number density has been undertaken to understand the contribution of Mo on the improvement of steel toughness.

Silencing Smad7 potentiates BMP2-induced chondrogenic differentiation and inhibits endochondral ossification in human synovial-derived mesenchymal stromal cells.

BACKGROUND: Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factor for cartilage tissue-engineering, but it also induces robust endochondral ossification. Human synovial-derived mesenchymal stromal cells (hSMSCs) have attracted great interest due to their poor potential for differentiation into osteogenic lineages. Smad7 plays a significant in the endochondral ossification. In this study, we explored a new method to amplify the BMP2-induced chondrogenic differentiation of hSMSCs by downregulating Smad7 and applying a cellular scaffold. METHODS: hSMSCs were isolated from human knee joint synovium from 3 donors through adhesion growth. In vitro and in vivo models of the chondrogenic differentiation of hSMSCs were established. Transgenic expression of BMP2 and silencing of Smad7 and Smad7 was achieved by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining, and RT-PCR analysis of the osteogenic genes RUNX2, Osterix, and Osteocalcin. The chondrogenic differentiation was detected by Alcian blue staining and RT-PCR analysis of the chondrogenic genes SOX9, COL2, and aggrecan. Hypertrophic differentiation was detected by the markers COL10 and MMP13. A subcutaneous stem cell implantation model was established with polyethylene glycol citrate-co-N-isopropylacrylamide (PPCN) scaffolds and athymic nude mice (3/group, 4-6 week-old female) and evaluated by micro-CT, H&E staining, and Alcian blue staining. An immunohistochemistry assay was used to detected COL1 and COL2, and an immunofluorescence assay was used to detect COL10 and MMP13. RESULTS: These hSMSCs identified by flow cytometry. These hSMSCs exhibited lower osteo-differentiation potential than iMads and C3H10T1/2-cells. When Smad7 was silenced in BMP2-induced hSMSCs, the chondrogenic differentiation genes SOX9, COL2, and aggrecan were enhanced in vitro. Additionally, it silencing Smad7 led to a decrease in the hypertrophic differentiation genes COL10 and MMP13. In subcutaneous stem cell implantation assays, immunofluorescence and immunohistochemical staining demonstrated that silencing Smad7 increased the number of COL2-positive cells and decreased the expression of COL1, COL10, and MMP13. CONCLUSION: This study suggests that the application of hSMSCs, cell scaffolds, and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibiting the expression of Smad7 in BMP2-induced hSMSC differentiation may be a new strategy for cartilage tissue-engineering.

Unveiling Hg-binding protein within black deposit formed on Golgi-Cox-stained brain neuron.

BACKGROUND: Golgi-Cox staining has been conventionally used for investigating neuronal development. After the brain tissue is subject to Golgi-Cox staining, black deposits are formed on the surface of the stained neurons because of mercuric sulfide, which does not show a fluorescence response under two-photon excitation. However, we unexpectedly observed fluorescence emitted by these black deposits during two-photon fluorescence measurements. Further, the in-depth of physical and chemical methods analysis revealed that the black deposits on the stained neurons are composed of Hg-binding proteins. METHODS: We studied black deposits present in the Golgi-Cox-stained mouse brain neurons using techniques such as multiple-photon microscopy, scan electron microscopy, micro-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. RESULTS: The emitted fluorescence was because of the fluorescence groups of Hg-binding protein present within the Golgi-Cox deposits on the neuronal surface. CONCLUSIONS: The presence of Hg-binding proteins within black deposits on the surface of Golgi-Cox-stained neurons was proven for the first time. The novel interaction between the neurons and Hg2+ ions during Golgi-Cox staining help to understand the mechanism of Golgi-Cox staining.

Hospital readmission after anterior cruciate ligament reconstruction: protocol for a systematic review and meta-analysis.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is one of the most common injuries of the knee. ACL reconstruction (ACLR) has been widely performed as a safe and effective treatment for ACL injuries. As there is an increasing trend in the incidence of ACL injury, hospital readmission after ACLR has attracted renewed attention for the financial burden to both patients and the healthcare system. However, information about hospital readmission after ACLR remains fragmented. Therefore, we plan to systematically review the literature to investigate the rate of, causes and risk factors for hospital readmission after ACLR, and summarise interventions to reduce hospital readmission. This article is to provide the protocol for an upcoming systematic review and meta-analysis on this important issue. METHODS AND ANALYSIS: Reporting of this protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. Electronic databases, including PubMed, Embase and the Cochrane Library, will be systematically searched from inception to June 2020. No language restrictions will be applied. Studies will be included if they reported hospital readmission or explored the associated potential causes and risk factors for hospital readmission after ACLR. The primary outcome will be the number and time frame of hospital readmission after ACLR. Secondary outcomes will be reasons for readmission, number and types of complications, risk factors for readmission and preventive measures for readmission after ACLR. Quality assessments will be performed by using the Newcastle-Ottawa Scale (NOS). If possible, study results will be summarised in a forest plot, and heterogeneity will be tested by using the Cochran's Q and I2 statistics. ETHICS AND DISSEMINATION: No ethical approval is required because our study is not related to patients or animals. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020058624.

Efficacy of a three-day prolonged-course of multiple-dose versus a single-dose of tranexamic acid in total hip and knee arthroplasty.

BACKGROUND: The application of tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA) has brought momentous changes in blood management. However, the optimal regimen of TXA has not yet been identified. This study aimed to compare the efficacy of a three-day prolonged-course of multiple-dose of TXA with a single pre-operative dose of TXA in patients who undergo THA and TKA. METHOD: We retrospectively analyzed two groups of consecutive patients who received primary unilateral THA and TKA from 2015 to 2017. One group received a three-day prolonged-course of multiple-dose of TXA, while another group received a single-dose of TXA. The primary outcomes included the changes in hemoglobin (Hb), estimated total blood loss (TBL), and transfusion rate; the secondary outcomes included the platelet (PLT) counts, inflammatory markers, and fibrinolysis parameters. RESULTS: A total of 193 THA and 166 TKA procedures were included for comparison. Compared with the patients who received a single-dose of TXA, the patients who received a three-day prolonged-course of multiple-dose of TXA had smaller post-operative drops in Hb levels, which led to consistently significantly higher Hb levels in both THA and TKA. Therefore, the use of multiple-dose of TXA was associated with significantly lower maximum Hb drops and estimated TBL in both THA (24.58±11.43 vs. 30.38±11.33 g/L, P=0.001; 685.88±412.02 vs. 968.94±479.9 mL, P<0.0001) and TKA (18.04±9.75 vs. 27.24±10.99 g/L, P<0.0001; 497.35±291.03 vs. 816.51±354.38 mL, P<0.0001), and marginally reduced transfusion requirements (THA: 1/65 vs. 10/128; TKA: 0/70 vs. 2/96). The multiple-dose group also showed higher PLT counts, continuously reduced inflammatory responses, and significantly and durably attenuated fibrinolytic responses. CONCLUSIONS: A three-day prolonged-course of multiple-dose of TXA was consistently effective in reducing post-operative Hb drops, estimated TBL, inflammatory responses, and fibrinolytic responses, which could be recommended for clinical practice. However, these findings need to be confirmed by prospective studies.

Are Routine Postoperative Laboratory Tests Necessary After Primary Total Hip Arthroplasty?

BACKGROUND: Recently, the practice of ordering routine postoperative laboratory tests in primary total hip arthroplasty (THA) has been challenged. This study aimed to evaluate the utility of routine postoperative laboratory tests after primary elective THA in an Asian population and identify the risk factors associated with abnormal postoperative laboratory test-related intervention. METHODS: We retrospectively reviewed 395 consecutive patients who underwent primary elective THA at a single tertiary academic center. Patient clinical information and laboratory test results were collected for analysis. RESULTS: A total of 349 (88.4%) patients had abnormal postoperative laboratory test results; most patients had anemia and hypoalbuminemia. Twenty-seven (6.8%) patients received clinical intervention. Of the 307 (77.7%) patients with postoperative anemia, 7 patients received blood transfusion. Factors associated with transfusion were female gender, low body mass index, long operation time, and low preoperative hemoglobin levels. Of the 149 (37.7%) patients with postoperative hypoalbuminemia, 16 received albumin supplementation. Factors associated with albumin supplementation were female gender, long operation time, and low preoperative albumin levels. Although 36 patients had abnormal postoperative creatinine, only 1 patient required specialist consultation. For electrolyte abnormalities, hyponatremia was noted; however, no patient received sodium supplementation. Moreover, 14 patients developed hypokalemia, of which 6 required potassium supplementation; 163 patients had hypocalcemia, of which 2 received calcium supplementation. CONCLUSION: Routine laboratory tests after primary elective THA are unnecessary for most of the patients in modern clinical practice. However, for those with identified risk factors, postoperative laboratory tests still should be performed.

Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain.

BACKGROUND: Identifying how pain transitions from acute to chronic is critical in designing effective prevention and management techniques for patients' well-being, physically, psychosocially, and financially. There is an increasingly pressing need for a quantitative and predictive method to evaluate how low back pain trajectories are classified and, subsequently, how we can more effectively intervene during these progression stages. METHODS: In order to better understand pain mechanisms, we investigated, using computational modeling, how best to describe pain trajectories by developing a platform by which we studied the transition of acute chronic pain. RESULTS: The present study uses a computational neuroscience-based method to conduct such trajectory research, motivated by the use of hypothalamic-pituitary-adrenal (HPA) axis activity-history over a time-period as a way to mimic pain trajectories. A numerical simulation study is presented as a "proof of concept" for this modeling approach. CONCLUSIONS: This model and its simulation results have highlighted the feasibility and the potential of developing such a broader model for patient evaluations.

The necessity of routine postoperative laboratory tests in enhanced recovery after surgery for primary hip and knee arthroplasty: A retrospective cohort study protocol.

INTRODUCTION: Over the last few decades, the concepts of minimally invasive surgery and enhanced recovery after surgery (ERAS) protocols have been introduced into the field of total joint arthroplasty (TJA), and tranexamic acid (TXA) has been widely used in TJA. Modern-day surgical techniques and perioperative care pathways of TJA have experienced unexpected improvements. Recently, the necessity of the practice of ordering routine postoperative laboratory tests for patients undergoing primary TJA has been challenged, especially in the context of implementation of ERAS protocols in TJA. These studies have consistently suggested that routine postoperative laboratory tests are not necessary in modern-day primary, unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA), and laboratory tests after surgery should only be obtained for patients with risk factors. However, it remains unclear whether routine postoperative laboratory tests after THA and TKA remains justified in the Chinese patient population. Therefore, we developed this study to address this issue. METHODS AND ANALYSIS: This retrospective cohort study will include adult patients who underwent primary unilateral THA or TKA and received multimodal perioperative care pathways according to ERAS protocols. The following patient data will be collected from the electronic medical record system: patients' demographics, preoperative and postoperative laboratory values, operation time, intraoperative blood loss, TXA use, tourniquet use, postoperative length of stay, and any medical intervention directly related to abnormal laboratory values. The main study outcomes are the incidence of acute anemia requiring transfusion and incidence of hypoalbuminemia requiring albumin supplementation. The secondary outcomes are the rates of acute kidney injury, incidence of abnormal serum sodium level, incidence of abnormal serum potassium level, and incidence of abnormal serum calcium level. These clinical data will be analyzed to determine the incidence of abnormal postoperative laboratory values following primary unilateral THA and TKA; to clarify the frequency of any medical intervention directly related to abnormal postoperative laboratory values; and to identify risk factors that predispose patients to have abnormal postoperative laboratory results. STUDY REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1900020690.

Overexpression of CD64 on CD14++CD16- and CD14++CD16+ monocytes of rheumatoid arthritis patients correlates with disease activity.

It is well-known that monocytes are a heterogeneous cell population and different monocyte subsets play important roles in rheumatoid arthritis (RA). Cluster of differentiation (CD)64 is one of Fc receptor, which initiates immunological and inflammatory reactions. However, the roles in RA remain to be elucidated. In the present study, the expression of CD64, CD40, CD163, CD206, HLA-DR, CD80 and CD86 on monocytes and the expression of CD64 on monocyte subsets were determined by flow cytometry. The expression of CD64 on monocyte subsets in patients with RA was further analyzed for their correlation with markers of autoimmune response, inflammation, disease activity of RA and serum cytokines. Compared to the health volunteers, the expression of CD64 on monocytes and each monocyte subset were significantly elevated in RA patients. The expression of CD64 on CD14++CD16- and CD14++CD16+ monocytes were positively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and disease activity score 28 (DAS28). Furthermore, the expression of CD64 on CD14++CD16+ monocytes was found to be associated with the serum level of IL-6. In conclusions, these data demonstrated the expression of CD64 on CD14++CD16- and CD14++CD16+ monocytes are elevated and associated with the disease activity in RA.