Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

2-Bromo-1,4-Naphthalenedione promotes CD8+ T cell expansion and limits Th1/Th17 to mitigate experimental autoimmune encephalomyelitis.

Treating Multiple sclerosis (MS), a well-known immune-mediated disease characterized by axonal demyelination, is challenging due to its complex causes. Naphthalenedione, present in numerous plants, is being explored as a potential medicine for MS due to its immunomodulatory properties. However, its effects on lymphocytes can vary depending on factors such as the specific compound, concentration, and experimental conditions. In this study, we aim to explore the therapeutic potential of 2-bromo-1,4-naphthalenedione (BrQ), a derivative of naphthalenedione, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and to elucidate its underlying mechanisms. We observed that mice treated with BrQ exhibited reduced severity of EAE symptoms, including lower clinical scores, decreased leukocyte infiltration, and less extensive demyelination in central nervous system. Furthermore, it was noted that BrQ does not directly affect the remyelination process. Through cell-chat analysis based on bulk RNA-seq data, coupled with validation of flow analysis, we discovered that BrQ significantly promotes the expansion of CD8+ T cells and their interactions with other immune cells in peripheral immune system in EAE mice. Subsequent CD8+ T cell depletion experiments confirmed that BrQ alleviates EAE in a CD8+ T cell-dependent manner. Mechanistically, expanded CD8+ cells were found to selectively reduce antigen-specific CD4+ cells and subsequently inhibit Th1 and Th17 cell development in vivo, ultimately leading to relief from EAE. In summary, our findings highlight the crucial role of BrQ in modulating the pathogenesis of MS, suggesting its potential as a novel drug candidate for treating MS and other autoimmune diseases.

Fabrication of fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots coupled with smartphone readout for tyramine determination in fermented meat products.

A fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots (r-BCDs@MIPs) was developed to detect tyramine in fermented meat products. The red emissive biomass-derived carbon dots (r-BCDs) were synthesized by the one-step solvothermal method using discarded passion fruit shells as raw materials. The fluorescence emission peak of r-BCDs was at 670 nm, and the relative quantum yield (QY) was about 2.44%. Molecularly imprinted sensing materials were prepared with r-BCDs as fluorescent centers for the detection of trace tyramine, which showed a good linear response in the concentration range of tyramine from 1 to 40 µg L-1. The linear correlation coefficient was 0.9837, and the limit of detection was 0.77 µg L-1. The method was successfully applied to the determination of tyramine in fermented meat products, and the recovery was 87.17-106.02%. The reliability of the results was verified through high-performance liquid chromatography (HPLC). Furthermore, we combined the r-BCDs@MIPs with smartphone-assisted signal readout to achieve real-time detection of tyramine in real samples. Considering its simplicity and convenience, the method could be used as a rapid and low-cost promising platform with broad application prospects for on-site detection of trace tyramine with smartphone-assisted signal readout.

Metabolic Syndrome Components and Its Impact on Acute Kidney Injury after Total Joint Arthroplasty.

BACKGROUND: Metabolic syndrome (MetS) is an independent risk factor for postoperative complications. This study aimed to evaluate the associated risk of MetS for perioperative complications, especially urinary complications, in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used a publicly available all-payer administrative database to identify patients undergoing TKA and THA from 2016 to 2020. The primary exposure of interest was MetS. Multivariable adjusted models based on propensity score matching were used to evaluate the association of MetS components with acute kidney injury (AKI), urinary tract infection (UTI), and acute posthemorrhagic anemia (APHA) in patients who underwent TKA and THA. A Counterfactual-Based Mediation Analysis was conducted to investigate the mediating effect of APHA on the relationship between MetS and AKI. RESULTS: The analysis included 2,097,940 (16.4% with MetS) THA and 3,073,310 (24.0% with MetS) TKA adult hospitalizations. Multivariable adjustment analysis indicated MetS was associated with an increased risk of AKI (OR [odds ratio] 1.78, 95% CI [confidence interval]1.69 to 1.89 for THA; OR 1.88, 95% CI 1.79 to 1.96 for TKA), UTI (OR 1.13, 95% CI 1.03 to 1.23 for THA; OR 1.26, 95% CI 1.17 to 1.35 for TKA), and APHA (OR 1.17, 95% CI 1.14 to 1.20 for THA; OR 1.7, 95% CI 1.15 to 1.19 for TKA). The risk of AKI increased with the number of MetS components, with odds ratios ranging from 2.58 to 9.46 in TKA patients and from 2.22 to 5.75 in THA patients. This increase was particularly associated with diabetes and hypertension, which were the most significant associated risk factors. Furthermore, APHA mediated the association between MetS and AKI. CONCLUSION: The prevalence of MetS is increasing in TKA and THA patients. Metabolic syndrome was associated with increased risk of AKI, UTI, and APHA. The risk of AKI increased with each additional MetS component, with diabetes and hypertension contributing most. In addition, APHA may play a partial mediating role in MetS-induced AKI.

Combining reverse end-to-side neurorrhaphy with rapamycin treatment on chronically denervated muscle in rats.

This preliminary research determines whether a combination of reverse end-to-side neurorrhaphy and rapamycin treatment achieves a better functional outcome than a single application after prolonged peripheral nerve injury. We found that the tibial nerve function of the reverse end-to-side + rapamycin group recovered better, with a higher tibial function index value, higher amplitude recovery rate, and shorter latency delay rate (P < 0.05). The reverse end-to-side + rapamycin group better protected the gastrocnemius muscle with more forceful contractility, tetanic tension, and a higher myofibril cross-sectional area (P < 0.05). Combining reverse end-to-side neurorrhaphy with rapamycin treatment is a practical approach to promoting the recovery of chronically denervated muscle atrophy after peripheral nerve injury.

Alcohol Withdrawal Is Associated With Worse Outcomes in Patients Undergoing Primary Total Knee or Total Hip Arthroplasty.

BACKGROUND: Alcohol withdrawal (AW) syndrome is an independent risk factor for postoperative complications. This study aims to evaluate the influence of AW on perioperative outcomes in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used the National Inpatient Sample database to identify patients undergoing TKA/THA from 2003 to 2014. The primary exposure of interest was AW. Multivariable adjusted models were used to evaluate the association of AW with in-hospital medical complications, surgical complications, mortality, cost, and length of stay (LOS) in patients undergoing TKA/THA. RESULTS: There were 2,971,539 adult hospitalizations for THAs and 6,367,713 hospitalizations for TKAs included in the present study, among which 0.14% of AW for THA patients and 0.10% of AW for TKA patients. Multivariable adjustment analysis suggested that AW was associated with an increased risk of medical complications (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.79-2.42, P < .0001), surgical complications (OR 1.75, 95% CI 1.51-2.03, P < .0001), and had 4.79 times increase of in-hospital mortality, 26% increase of total cost, and 53% increase of LOS in THA procedures. For TKA procedures, AW was also associated with increased risk of medical complications (OR 3.14, 95% CI 2.78-3.56, P < .0001), surgical complications (OR 2.07, 95% CI 1.82-2.34, P < .0001) and 4.24 times increase of in-hospital mortality, 29% increase of total cost, and 58% increase of LOS after multivariable adjustment. CONCLUSION: AW is associated with increased risk of in-hospital mortality, medical and surgical complications. Proactive surveillance and management of AW may be important in improving outcomes in patients who underwent THA and TKA procedure.

Endosialin defines human stem Leydig cells with regenerative potential.

STUDY QUESTION: Is endosialin a specific marker of human stem Leydig cells (SLCs) with the ability to differentiate into testosterone-producing Leydig cells (LCs) in vitro and in vivo? SUMMARY ANSWER: Endosialin is a specific marker of human SLCs which differentiate into testosterone-producing LCs in vitro and in vivo. WHAT IS KNOWN ALREADY: Human SLCs have been identified and isolated using the marker platelet-derived growth factor receptor α (PDGFRα) or nerve growth factor receptor (NGFR). However, the specificity was not high; thus, LCs and germ cells could be mistakenly sorted as SLCs if PDGFRα or NGFR was used as a marker for human SLCs isolation. STUDY DESIGN, SIZE, DURATION: Firstly, we re-evaluated the specificity of PDGFRα and NGFR for SLCs in adult human testes. Then we analysed the previously published single-cell sequencing data and found that endosialin may identify human SLCs. Subsequently, we sorted endosialin+ cells from four human donors and characterized their self-renewal and multipotent properties. To assess whether endosialin+ cells have the potential to differentiate into functional LCs in vitro, these cells were stimulated by differentiation-inducing medium. We next assessed the in vivo regenerative potential of human endosialin+ cells after xenotransplantation into the testes of immunodeficient mice. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single-cell sequencing analysis, immunofluorescence and flow cytometry were used to characterize human testis tissues. In vitro colony formation, multipotent differentiation (adipogenic, osteogenic and chondrogenic) and Leydig cell-lineage induction were used to assess stem cell activity. Xenotransplantation into 3-week-old immunodeficient mice was used to determine in vivo regenerative potential. Endpoint measures included testosterone measurements, cell proliferation, immunofluorescence, flow cytometry and quantitative RT-PCR. MAIN RESULTS AND THE ROLE OF CHANCE: The results indicate that endosialin is a specific marker of SLCs compared with PDGFRα and NGFR. Additionally, endosialin+ cells isolated from human testes show extensive proliferation and differentiation potential in vitro: their self-renewal ability was inferred by the formation of spherical clones derived from a single cell. Moreover, these cells could differentiate into functional LCs that secreted testosterone in response to LH in a concentration-dependent manner in vitro. These self-renewal and differentiation properties reinforce the proposal that human testicular endosialin+ cells are SLCs. Furthermore, transplanted human endosialin+ cells appear to colonize the murine host testes, localize to peritubular and perivascular regions, proliferate measurably and differentiate partially into testosterone-producing LCs in vivo. LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: Owing to the difficulty in collecting human testis tissue, the sample size was limited. The functions of endosialin on SLCs need to be elucidated in future studies. WIDER IMPLICATIONS OF THE FINDINGS: A discriminatory marker, endosialin, for human SLCs purification is a prerequisite to advance research in SLCs and logically promote further clinical translation of SLCs-based therapies for male hypogonadism. STUDY FUNDING/COMPETING INTEREST(S): A.P.X. was supported by the National Key Research and Development Program of China (2017YFA0103802 and 2018YFA0107200). C.D. was supported by the National Natural Science Foundation of China (81971314) and the Natural Science Foundation of Guangdong Province, China (2018B030311039). The authors declare no conflict of interest.

How to predict early clinical outcomes and evaluate the quality of primary total knee arthroplasty: a new scoring system based on lower-extremity angles of alignment.

BACKGROUND: A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient's surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. METHODS: We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. RESULTS: We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: "A" = PGGCO ≥0.8, "B" = PGGCO ≤0.6 but < 0.8, and "C" = PGGCO < 0.6. The scoring system performed well in external validation. CONCLUSIONS: This study first developed a validated, evidence-based scoring system based on lower-extremity angles of alignment to predict early clinical outcomes and to objectively evaluate the quality of TKA.

Alterations of kinematics in knees after single versus multiple radius femoral prostheses total knee arthroplasty: a retrospective study.

BACKGROUND: Design modifications in prostheses may cause alterations in gait kinematics, thus influencing functional restoration of knees after total knee arthroplasty (TKA). The aim of the study was to investigate the differences in gait kinematics and clinical outcomes after single radius (SR) versus multiple radius (MR) TKA. METHOD: The present retrospective study included 38 unilateral TKA involving 20 knees using MR design implant and 18 knees using SR design implant. Thirty-six healthy volunteers were also recruited. The mean follow-up time was 16 ± 3 months. At the end of follow-up, the 6 degrees of freedom (DOF) kinematics of knees and range of motion (ROM) were measured with a portable optical tracking system. Knee society score (KSS) and knee injury, and osteoarthritis outcome score (KOOS) were also collected. RESULTS: Patients in the SR group had significantly higher scores in activities of daily living (84.7 ± 15.9) and sports and recreation (67.5 ± 25.2) KOOS sub-score than MR group (69.9 ± 17.6, P = 0.012; 50.0 ± 20.8, P = 0.027, respectively). Significant differences were detected between MR knees and SR knees (1.82° ± 3.11° vs 4.93° ± 3.58°, P = 0.009), and MR knees and healthy knees (1.82° ± 3.11° vs 3.62° ± 3.52°, P = 0.032) in adduction/abduction ROM. The proximal/distal translation was significantly smaller in MR knees (0.58 ± 0.54 cm) compared with SR knees (1.03 ± 0.53 cm, P = 0.003) or healthy knees (0.84 ± 0.45 cm, P = 0.039). SR knees (0.24 ± 0.40 cm) had smaller translation compared with the MR group (0.54 ± 0.33 cm, P = 0.017) and control group (0.67 ± 0.36 cm, P = 0.028). No significant difference was detected in the other DOFs during the gait cycle. Significant difference was detected in extension/flexion, internal/external rotation, adduction/abduction, proximal/distal and medial/lateral among MR, SR and healthy knees. CONCLUSION: After TKA, patients have altered gait kinematics compared with the control group. MR and SR design showed varied characteristics in 6 DOF gait kinematics, which could be the cause of the difference in functional outcome.

Preoperative transthoracic echocardiography does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients.

PURPOSE: The present study aimed to investigate the influence of preoperative TTE on postoperative short-term mortality, surgery delay, as well as other economic and clinical outcomes in Chinese geriatric hip fracture patients. METHODS: This retrospective, matched-cohort study enrolled geriatric hip fracture patients (≥ 60 years) who underwent surgical interventions at our center between 2015 and 2020. The primary exposure was inpatient preoperative TTE. Demographic and clinical data that were reported as risk factors for postoperative mortality were retrieved from the medical data center as the covariates. The primary clinical outcomes were all-cause mortality at 30 days, 90 days, 180 days, and 1 year. Time from hospital presentation to surgery, length of stay (LOS), inpatient cost, frequency of cardiology consultation and coronary angiography (CAG) were also assessed. The propensity score matching (PSM) was performed in a ratio of 1:1. RESULTS: 447 patients were identified and 216 of them received a preoperative TTE (48.3%). After successfully matching 390 patients (87.2%), patients receiving TTE showed significantly higher 30-day mortality (6.6% vs 2.0%, P = 0.044). But no significant difference was found in 90-day, 180-day, and 365-day mortality as well as the 1-year accumulated survival rate. Receipt of TTE was also associated with significant increases in LOS (13.6 days vs 11.4 days, P = 0.017), waiting time for surgery (5.9 days vs 4.3 days, P < 0.001), and lower proportion of receiving surgery within 48 h (7.2% vs. 26.2%, P < 0.001). According to the multivariable logistic analysis, only ejection fraction (30 days, 90 days), aorta diameter (30 days, 90 days, 180 days, 365 days), left ventricular posterior wall diameter (90 days, 180 days, 365 days), aortic valve velocity (90 days) and mitral valve A-peak (90 days, 180 days) were association with postoperative mortality among the 17 parameters in the TTE reports. Besides, TTE has no influence on the frequency of preoperative cardiology consultation. CONCLUSION: Preoperative TTE does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients. The predictive ability of TTE parameters is limited for postoperative mortality.

A smartphone-combined ratiometric fluorescence molecularly imprinted probe based on biomass-derived carbon dots for determination of tyramine in fermented meat products.

A ratiometric fluorescence molecularly imprinted probe employing two distinct emission wavelengths of biomass carbon dots was developed for highly selective and visual quantitative detection of tyramine in fermented meat products. The red emission biomass carbon dots were employed as responsive elements, and the blue ones were utilized as the reference elements. The molecularly imprinted polymers were incorporated in the ratiometric sensing to distinguish and adsorb tyramine. With the linear range of 1-60 µg/L, the ratiometric fluorescence molecularly imprinted probe was successfully applied to detect tyramine in real samples with the satisfactory recoveries of 79.74-112.12% and the detect limitation of 1.3 µg/kg, indicating that this probe has great potential applications for the detection of tyramine in real samples. Moreover, smartphone-based fluorescence signal recognition analysis on hand has been developed for the quantitative analysis of tyramine, providing a portable visual optical analysis terminal for rapid on-site determination of tyramine.

ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Angle-Insensitive Ultrathin Broadband Visible Absorber Based on Dielectric-Semiconductor-Lossy Metal Film Stacks.

Ultrathin broadband absorbers with high efficiency, wide angular tolerance, and low fabrication cost are in demand for various applications. Here, we present an angle-insensitive ultrathin (<150 nm) broadband absorber with an average 96.88% (experiment) absorptivity in the whole visible range by utilizing a simple dielectric-semiconductor-lossy metal triple-layer film structure. The excellent broadband absorption performance of the device results from the combined action of the enhanced absorptions in the semiconductor and lossy metal layers exploiting strong interference effects and can be maintained over a wide viewing angle up to ±60°. Benefiting from the lossy metal providing additional absorption, our design reduces the requirement for the semiconductor's material dispersion and has great flexibility in the material selection of the metal layer. Additionally, the lithography-free nature of the proposed broadband visible absorber provides a high-throughput fabrication convenience, thus holding great potential for its large-area applications in various fields.

Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis.

INTRODUCTION: Accumulated clinical trials had been focused on stem cell therapy in combination of core decompression (CD) in the treatment of avascular necrosis of the femoral head (ANFH). Nonetheless, the results were inconclusive. Here, we performed a systematic review and meta-analysis of previous randomized controlled trials (RCTs) and retrospective studies to assess whether combined stem cell augmentation with CD improved the outcomes of ANFH compared with CD alone. METHODS: The current study included 11 RCTs and 7 retrospective studies reporting the clinical outcomes of a total of 916 patients and 1257 hips. 557 and 700 hips received CD and CD plus stem cell therapy, respectively. To compare CD with CD plus stem cell therapy, we examined the clinical evaluating scores, the occurrence of the femoral head, radiologic progression and conversion to total hip arthroplasty (THA). RESULTS: Only 10 studies reported significantly greater improvement in hip functions while combining stem cell procedure with CD. The pooled results in subgroup analysis indicated that stem cell group had a lower collapse rate on a mid-term basis (P = 0.001), when combined with mechanical support (P < 0.00001), and with extracted stem cells (P = 0.0002). Likewise, stem cell group had a lower radiographic progression rate at 2- to 5-year follow-up [P = 0.003], when combined with structural grafting (P < 0.00001), and with extracted stem cells (P = 0.004). Stem cell therapy resulted in an overall lower THA conversion rate (P < 0.0001) except that at a follow-up longer than 5 years. CONCLUSION: Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression and conversion to THA. Trial Registration The current protocol has been registered in PROSPERO with the registration number: CRD42023417248.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

Baseline Knee Pain Predicts Long-Term Response of Intra-Articular Steroid Injection in Symptomatic Knee Osteoarthritis: Data from OAI.

OBJECTIVE: The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). METHODS: Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. RESULTS: The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. CONCLUSION: KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.

Preoperative Vitamin D Deficiency is Associated with Increased One-Year Mortality in Chinese Geriatric Hip Fracture Patients - A Propensity Score Matching Study.

Background: Vitamin D deficiency is a common comorbidity in geriatric hip fracture patients. However, there is still an ongoing debate regarding the influence of preoperative Vitamin D status on postoperative mortality in hip fracture patients. Methods: Elderly patients (≥60 years) who underwent surgical interventions for unilateral hip fracture from 2015 to 2020 in our center were included. We retrospectively retrieved the demographic data from the electronic medical database. Preoperative serum total 25-hydroxy-Vitamin D was set as the independent variable and patients were classified as the Vitamin D deficiency (<20ng/mL) and the control groups consequently. Clinical outcomes include all-cause mortality, walking ability, and major postoperative complications in the first postoperative year. Propensity score matching (PSM) was performed in a ratio of 1:1 in the two groups for further comparison. Results: A total of 210 patients were included and 121 patients (57.6%) were diagnosed with Vitamin D deficiency. Patients in the Vitamin D deficiency group were much older and therefore preferred peripheral nerve block, and had significantly higher proportions of females, preoperative dementia, higher ASA grade, and lower baseline serum albumin level. Overall, 79 patients were identified in the Vitamin D deficiency and control groups after PSM, respectively. Patients diagnosed with Vitamin D deficiency showed a significantly higher one-year mortality (21.5% vs 6.3%, P=0.011) and a much lower one-year independent walking rate (67.1% vs.84.8%, P=0.016) after the matching. Regarding the dataset before PSM and after PSM, the AUC for serum Vitamin D for predicting one-year mortality was 0.656 (P=0.006) and 0.695 (P=0.002), respectively. Conclusion: Our retrospective PSM-design study provides new evidence that Vitamin D deficiency was associated with a significantly higher mortality and poor walking ability in the first year after surgical intervention based on southern Chinese populations.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the "prosthetic microenvironment". In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.