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Background Musculoskeletal tissue degeneration impairs the life quality and motor function of many people, especially seniors and athletes. Tendinopathy is one of the most common diseases associated with musculoskeletal tissue degeneration, representing a major global healthcare burden that affects both athletes and the general population, with the clinical presentation of long-term recurring chronic pain and decreased tolerance to activity. The cellular and molecular mechanisms at the basis of the disease process remain elusive. Here, we use a single-cell and spatial RNA sequencing approach to provide a further understanding of cellular heterogeneity and molecular mechanisms underlying tendinopathy progression. Results To explore the changes in tendon homeostasis during the tendinopathy process, we built a cell atlas of healthy and diseased human tendons using single-cell RNA sequencing of approximately 35,000 cells and explored the variations of cell subtypes’ spatial distributions using spatial RNA sequencing. We identified and localized different tenocyte subpopulations in normal and lesioned tendons, found different differentiation trajectories of tendon stem/progenitor cells in normal/diseased tendons, and revealed the spatial location relationship between stromal cells and diseased tenocytes. We deciphered the progression of tendinopathy at a single-cell level, which is characterized by inflammatory infiltration, followed by chondrogenesis and finally endochondral ossification. We found diseased tissue-specific endothelial cell subsets and macrophages as potential therapeutic targets. Conclusions This cell atlas provides the molecular foundation for investigating how tendon cell identities, biochemical functions, and interactions contributed to the tendinopathy process. The discoveries revealed the pathogenesis of tendinopathy at single-cell and spatial levels, which is characterized by inflammatory infiltration, followed by chondrogenesis, and finally endochondral ossification. Our results provide new insights into the control of tendinopathy and potential clues to developing novel diagnostic and therapeutic strategies.

Background Acute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms. Methods 10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot. Results Proteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis. Conclusions Comprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis.

Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive. We built a cell atlas of 12 healthy or degenerated human meniscus samples from the inner and outer meniscal zones of 8 patients using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging. We identified and localized cell types in inner and outer meniscus and found new chondrocyte subtypes associated with degeneration. The observations suggested understandings on how cellular compositions, functions, and interactions participated in degeneration, and on the possible loop-like interactions among extracellular matrix disassembly, angiogenesis, and inflammation in driving the degeneration. The study provided a rich resource reflecting variations in the meniscal microenvironment during degeneration and suggested new cell subtypes as potential therapeutic targets. The hypothesized mechanism could also be a general model for other joint degenerations. The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003), the National Key Research and Development Program of China (2021YFF1200901), Fundamental Research Funds for the Central Universities (2015SCU04A40); The Innovative Spark Project of Sichuan University (2018SCUH0034); Sichuan Science and Technology Program (2020YFH0075); Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN); 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301); 1.3.5 Project for Disciplines of Excellence - Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH039).

To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression. Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining. We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease. This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies. This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

Background Medial patellofemoral ligament (MPFL) reconstruction combined with tibial tubercle osteotomy (TTO) and lateral retinacular release (LRR) is one of the main treatment methods for patellar instability. So far, few studies have evaluated the clinical effectiveness and assessed potential risk factors for recurrent patellar instability. Purpose To report the clinical outcomes of MPFL reconstruction combined with TTO and LRR at least three years after operation and to identify potential risk factors for recurrent patellar instability. Methods A retrospective analysis of medical records for patients treated with MPFL, TTO and LRR from 2013 to 2017 was performed. Preoperative assessment for imaging examination included trochlear dysplasia according to Dejour classification, patella alta with the Caton-Deschamps index (CDI), tibial tubercle–trochlear groove distance. Postoperative assessment for knee function included Kujala, IKDC and Tegner scores. Failure rate which was defined by a postoperative dislocation was also reported. Results A total of 108 knees in 98 patients were included in the study. The mean age at operation was 19.2 ± 6.1 years (range, 13–40 years), and the mean follow-up was 61.3 ± 15.4 months (range, 36–92 months). All patients included had trochlear dysplasia (A, 24%; B, 17%; C, 35%; D, 24%), and 67% had patellar alta. The mean postoperative scores of Tegner, Kujala and IKDC were 5.3 ± 1.3 (2–8), 90.5 ± 15.5 (24–100) and 72.7 ± 12.1 (26–86). Postoperative dislocation happened in 6 patients (5.6%). Female gender was a risk factor for lower IKDC (70.7 vs 78.1, P  = 0.006), Tegner (5.1 vs 6.0, P  = 0.006) and Kujala (88.2 vs 96.6, P  = 0.008). Age ( p  = 0.011) and trochlear dysplasia ( p  = 0.016) were considered to be two failure factors for MPFL combined with TTO and LRR. Conclusion As a surgical method, MPFL combined with TTO and LRR would be a reliable choice with a low failure rate (5.6%). Female gender was a risk factor for worse postoperative outcomes. Preoperative failure risk factors in this study were age and trochlear dysplasia. Level of Evidence Level IV; Case series

Nonaromatic and nonconjugated fluorescent materials have garnered increasing attention in recent years. However, most non-classical chromophores are derived from electro-rich nitrogen and oxygen atoms, which suffer from short emission wavelengths, low efficiency, limited responsiveness, and obscure luminescence mechanisms. Here we present an emission mechanism in bioactive polycysteine, an aliphatic polymer that displays polymerization- and aggregation-induced emission, high quantum yield, and multicolor emission properties. We show that the hydrogen atoms bonded to the sulfur atoms play a crucial role in luminescence. This enables reversible modulation of polymer fluorescence under reducing and oxidizing conditions, facilitating specific imaging and quantitative detection of redox species in cells and in vivo. Furthermore, the polymer exhibits better anti-inflammatory and antioxidative activities compared to first-line clinical antioxidants, offering a promising platform for in vivo theragnosis of diseases such as osteoarthritis. Nonaromatic and nonconjugated fluorescent materials are promising for in vivo uses, but usually have low fluorescence quantum yields and limited responsiveness. Here, the authors report a polycysteine derived from natural amino acids that displays intrinsic fluorescence, color switching properties and applicability as a drug-free and self-reporting system for the theragnosis of osteoarthritis.

Large Language Models (LLMs) show promise in healthcare tasks but face challenges in complex medical scenarios. We developed a Multi-Agent Conversation (MAC) framework for disease diagnosis, inspired by clinical Multi-Disciplinary Team discussions. Using 302 rare disease cases, we evaluated GPT-3.5, GPT-4, and MAC on medical knowledge and clinical reasoning. MAC outperformed single models in both primary and follow-up consultations, achieving higher accuracy in diagnoses and suggested tests. Optimal performance was achieved with four doctor agents and a supervisor agent, using GPT-4 as the base model. MAC demonstrated high consistency across repeated runs. Further comparative analysis showed MAC also outperformed other methods including Chain of Thoughts (CoT), Self-Refine, and Self-Consistency with higher performance and more output tokens. This framework significantly enhanced LLMs’ diagnostic capabilities, effectively bridging theoretical knowledge and practical clinical application. Our findings highlight the potential of multi-agent LLMs in healthcare and suggest further research into their clinical implementation.

Purpose This study aimed to evaluate the efficacy of arthroscopic sciatic neurolysis for treating deep gluteal syndrome (DGS) and to analyse the application value of high-frequency ultrasound during perioperative period. Methods Between June 2020 and February 2022, 30 patients with DGS who underwent failed conservative treatment were retrospectively analysed. Lateral arthroscopic exploration of the deep gluteal space and sciatic neurolysis were performed. In addition to pelvic X-ray, lumbar disc and hip magnetic resonance imaging (MRI), ultrasonography of the sciatic nerve was also performed in all patients. The visual analogue scale pain score (VAS), modified Harris hip score (mHHS) and Benson symptom-rating scale were used to evaluate the clinical efficacy. The correlation between preoperative sciatic nerve ultrasound and arthroscopic findings was analysed. Results The median follow-up for these patients was 13 months (range,12–21 months). Preoperative ultrasonography showed precise morphological changes in 26 sciatic nerves of patients. The VAS score decreased from 5.0 (4.0, 6.0) preoperatively to 0.5 (0, 1.0) postoperatively ( p  < 0.001), and the mHHS increased from 64.0 (57.0, 67.0) preoperatively to 95.0 (93.0, 97.0) postoperatively ( p  < 0.001). The Benson symptom score was excellent in 15 cases, good in 12 cases, fair in 2 cases, poor in 1 case; thus, the score was excellent or good in 90% of the cases. Preoperative ultrasound diagnosis and intra-operative findings matched up in all cases. There were four cases of transient numbness in the posterior thigh. Conclusions Arthroscopic sciatic neurolysis is a safe and effective treatment option for DGS patients who fail conservative treatment. Ultrasound diagnosis matched the arthroscopic findings perfectly. Preoperative Doppler ultrasound can assist surgical decision-making, guide intraoperative release.

This study aims to explore the risk factors associated with frozen shoulder (FS) and develop a predictive model for diagnosing FS, in order to facilitate early detection of the condition. A total of 103 patients diagnosed with FS and admitted to the Department of Joint Surgery at Suining Central Hospital between October 2021 and October 2023 were consecutively included in the study. Additionally, 309 individuals without shoulder joint diseases, matched for age and gender, who visited the department during the same time, were included as the control group.The complete recording of clinical data for all patients was followed by the utilization of statistical tests such as the Mann–Whitney U test, sample t test, and chi-square test to compare different groups. Additionally, multivariate binary logistic regression analysis was employed to identify risk factors associated with the occurrence of FS in patients, leading to the establishment of a prediction model and derivation of a simplified equation. The diagnostic effectiveness of individual indicators and prediction models was assessed through the use of receiver operating characteristic (ROC) curve analysis. In the sample of 103 individuals, 35 were identified as male and 68 as female, with an average age range of 40–70 years (mean age: 54.20 ± 6.82 years). The analysis conducted between different groups revealed that individuals with a low body mass index (BMI), in conjunction with other factors such as diabetes, cervical spondylosis, atherosclerosis, and hyperlipidemia, were more susceptible to developing FS. Logistic regression analysis further indicated that low BMI, diabetes, cervical spondylosis, and hyperlipidemia were significant risk factors for the occurrence of FS. These variables were subsequently incorporated into a predictive model, resulting in the creation of a simplified equation.The ROC curve demonstrated that the combined indicators in the predictive model exhibited superior diagnostic efficacy compared to single indicators, as evidenced by an area under the curve of 0.787, sensitivity of 62.1%, and specificity of 82.2%. Low BMI, diabetes, cervical spondylosis, and hyperlipidemia are significant risk factors associated with the occurrence of FS. Moreover, the utilization of a prediction model has demonstrated superior capability in forecasting the likelihood of FS compared to relying solely on individual indicators. This finding holds potential in offering valuable insights for the early diagnosis of FS.

Purpose FAI (femoroacetabular impingement syndrome) is a common cause of hip pain, resulting in a decreased life quality. This study aims to compare the postoperative clinical outcome between arthroscopic surgery (AT) and conservative treatment (CT). Method The six studies were selected from PubMed, Embase and OVID database. The data were extracted and analyzed by RevMan5.3. Mean differences and 95% confidence intervals were calculated. RevMan5.3 was used to assess the risk of bias. Result Six observational studies were assessed. The methodological quality of the trials indicated five of six studies had a low risk of bias and one article had a high risk of bias. The differences were statistically significant between AT and CT for HOS (follow-up for 6 months), iHOT-33 (follow-up for 6 months) improvement, iHOT-33 (follow-up for 12 months) improvement, iHOT-33 (follow-up for 12 months), EQ-5D-5L index score (follow-up for 12 months) and AT showed higher benefits than CT. Meanwhile no statistically significant were found in iHOT-33 (follow-up for 6 months), EQ-5D-5L index score (follow-up for 6 months), EQ5D-VAS (follow-up for 6 months) and EQ5D-VAS (follow-up for 12 months). Conclusion AT and CT both can have clinical effects when facing FAI. In our meta-analysis, hip arthroscopy is statistically superior to conservative treatment in both long-term and short-term effects.