The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study.

BACKGROUD: Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma lipids and alcohol intake frequency play a role in the development of OA. METHODS: The study employed a comprehensive genome-wide association database to identify independent genetic loci strongly linked to plasma lipids and alcohol intake frequency, which were used as instrumental variables. The causal association between plasma lipids, alcohol intake frequency, and the risk of OA was then analyzed using two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (ORs) as the evaluation criteria. RESULTS: A total of 392 SNPs were included as instrumental variables in this study, including 32 for total cholesterol (TC), 39 for triglycerides (TG), 170 for high-density lipoproteins (HDL), 60 for low-density lipoproteins (LDL), and 91 for alcohol intake frequency. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome, with the IVW method as the primary analysis method and other MR analysis methods complementing IVW. The results of this study showed that four exposure factors were causally associated with the risk of OA. TC obtained a statistically significant result for IVW (OR = 1.207, 95% CI: 1.018-1.431, P = 0.031); TG obtained a statistically significant result for Simple mode (OR = 1.855, 95% CI: 1.107-3.109, P = 0.024); LDL obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 1.363, 95% CI: 1.043-1.781, P = 0.023; WME: OR = 1.583, 95% CI: 1.088-2.303, P = 0.016; Weighted mode: OR = 1.521, 95% CI: 1.062-2.178, P = 0.026). Three statistically significant results were obtained for alcohol intake frequency with IVW, WME and Weighted mode (IVW: OR = 1.326, 95% CI: 1.047-1.678, P = 0.019; WME: OR = 1.477, 95% CI: 1.059-2.061, P = 0.022; Weighted mode: OR = 1.641, 95% CI: 1.060-2.541, P = 0.029). TC, TG, LDL, and alcohol intake frequency were all considered as risk factors for OA. The Cochran Q test for the IVW and MR-Egger methods indicated intergenic heterogeneity in the SNPs contained in TG, HDL, LDL, and alcohol intake frequency, and the test for pleiotropy indicated a weak likelihood of pleiotropy in all causal analyses. CONCLUSIONS: The results of two-sample Mendelian randomization analysis showed that TC, TG, LDL, and alcohol intake frequency were risk factors for OA, and the risk of OA increased with their rise.

Prevention, intervention, and management of physical training in the rehabilitation of lower limb injuries / Prevenção, intervenção e gerenciamento do treinamento físico na reabilitação de lesões nos membros inferiores / Prevención, intervención y gestión del entrenamiento físico en la rehabilitación de lesiones de los miembros inferiores

ABSTRACT Introduction Lower limb injuries are one of the main sports occurrences among athletes. Severe lower limb injuries will lead to the definitive end of the athlete's professional career. Objective Explore the mechanisms of prevention and intervention against lower limb injuries in physical training and the rehabilitation management strategies for lower limb injuries. Methods In this study, 20 athletes were selected. Comparing the results of the lower limb FMS test and balance y test before and after rehabilitation training management, the effect of rehabilitation management on recovery from lower limb injuries in physical training was discussed. Results Lower limb injury is a common type of sports injury in physical training; however, better recovery utilization can be achieved through successful rehabilitation training. Rehabilitation training management can effectively improve the FMS test score of athletes' lower limbs and the number of people who passed the Y balance test. However, the existing rehabilitation training program still has some limitations, which need to be corrected according to the individual conditions of athletes. Conclusion Through physical training and medical rehabilitation, athletes with lower limb injuries can recover their lower limb sports ability and prolong their sporting life. Therefore, it should be disseminated. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A lesão nos membros inferiores é uma das principais ocorrências esportivas entre os atletas. Lesões graves nos membros inferiores levarão ao encerramento definitivo da carreira profissional do atleta. Objetivo Explorar os mecanismos de prevenção e intervenção contra lesões dos membros inferiores no treinamento físico e as estratégias de gerenciamento de reabilitação para lesões dos membros inferiores. Métodos Neste trabalho, 20 atletas foram selecionados. Por meio da comparação dos resultados do teste FMS de membros inferiores e do teste de equilíbrio y antes e depois do gerenciamento do treinamento de reabilitação, foi discutido o efeito do gerenciamento de reabilitação na recuperação de lesões dos membros inferiores no treinamento físico. Resultados A lesão dos membros inferiores é um tipo corriqueiro de lesão esportiva no treinamento físico, porém um melhor aproveitamento da recuperação pode ser alcançado através de um treinamento de reabilitação bem-sucedido. O gerenciamento do treinamento de reabilitação pode efetivamente melhorar a pontuação do teste FMS dos membros inferiores dos atletas e o número de pessoas que passaram no teste de equilíbrio Y. Entretanto, o programa de treinamento de reabilitação existente ainda apresenta algumas limitações, que precisam ser corrigidas de acordo com as condições individuais dos atletas. Conclusão Através da combinação de treinamento físico e reabilitação médica, os atletas com lesão nos membros inferiores podem recuperar sua capacidade esportiva nos membros inferiores e prolongar uma vida esportiva. Portanto, convém difundi-lo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Las lesiones en los miembros inferiores son uno de los principales sucesos deportivos entre los atletas. Las lesiones graves en los miembros inferiores conducirán al final definitivo de la carrera profesional del atleta. Objetivo Explorar los mecanismos de prevención e intervención contra las lesiones de los miembros inferiores en el entrenamiento físico, y las estrategias de gestión de la rehabilitación de las lesiones de los miembros inferiores. Métodos En este estudio se seleccionaron 20 atletas. Mediante la comparación de los resultados de la prueba de FMS de las extremidades inferiores y la prueba de equilibrio y antes y después de la gestión del entrenamiento de rehabilitación, se analizó el efecto de la gestión de la rehabilitación en la recuperación de las lesiones de las extremidades inferiores en el entrenamiento físico. Resultados Las lesiones en las extremidades inferiores son un tipo de lesión deportiva común en el entrenamiento físico, sin embargo, se puede lograr una mejor utilización de la recuperación mediante un entrenamiento de rehabilitación exitoso. La gestión del entrenamiento de rehabilitación puede mejorar eficazmente las puntuaciones de los atletas en las pruebas de FMS de las extremidades inferiores y el número de personas que superan la prueba de equilibrio Y. Sin embargo, el programa de entrenamiento de rehabilitación existente sigue teniendo algunas limitaciones, que deben corregirse en función de las condiciones individuales de los deportistas. Conclusión Mediante la combinación de entrenamiento físico y rehabilitación médica, los atletas con lesiones en las extremidades inferiores pueden recuperar su capacidad deportiva y prolongar su vida deportiva. Por lo tanto, debe difundirse. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Recovery from muscle injurie after high-intensity training in table tennis / Recuperação de lesão muscular após treinamento de alta intensidade na prática do tênis de mesa / Recuperación de lesión muscular tras un entrenamiento de alta intensidad en el tenis de mesa

ABSTRACT Introduction High-intensity training is an important point in table tennis training. Due to the high muscle load, occasional injuries may occur during the practice of this activity, requiring the intervention of dedicated physical rehabilitation. Objective Explore the rehabilitation process of muscle injuries caused by high-intensity training in table tennis athletes. Methods Thirty-one student table tennis athletes with indications for rehabilitation due to muscle injuries caused by high-intensity training were volunteers for this research. Data pertinent to the research were collected before and after the intervention. Muscle strength, tank test, lifting test, flexor and extensor group peak torque at 60°/s speed, and flexor and extensor group peak torque at 60°/s speed were analyzed, and data were stored and analyzed in statistical software. The results were analyzed and checked against the updated scientific literature. Results The research shows that a good recovery method can relieve muscle pain and reduce psychological problems caused by pain and speed up joint motion gain. Conclusion The protocol analyzed in this paper can improve the athletes' sporting level both from the physiological and psychological point of view, besides promoting faster recovery and being suitable for daily practical application. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução O treino de alta intensidade é um ponto importante no treinamento do tênis de mesa. Devido à alta carga muscular, podem ocorrer lesões ocasionais durante a prática dessa atividade, exigindo a intervenção de uma reabilitação física dedicada. Objetivo Explorar o processo de reabilitação nas lesões musculares provocadas pelo treinamento de alta intensidade em atletas do tênis de mesa. Métodos Foram voluntários dessa pesquisa 31 estudantes atletas do tênis de mesa com indicação para reabilitação devido a lesões musculares ocasionadas pelo treinamento de alta intensidade. Os dados pertinentes a pesquisa foram coletados antes e após a intervenção. Foi analisada a força muscular, teste de tanque, teste de levantamento, o torque de pico do grupo flexor e extensor à velocidade de 60°/s e o torque de pico do grupo flexor e extensor à velocidade de 60°/s, os dados foram armazenados e analisados em software estatístico. Os resultados foram analisados e confrontados à bibliografia científica atualizada. Resultados A pesquisa mostra que um bom método de recuperação pode não só aliviar a dor muscular e reduzir os problemas psicológicos causados pela dor, como também pode agilizar o ganho de movimento articular. Conclusão O protocolo analisado neste trabalho pode melhorar o nível esportivo dos atletas tanto do ponto de vista fisiológico quanto psicológico além de promover uma recuperação mais rápida, sendo apta na aplicação prática cotidiana. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El entrenamiento de alta intensidad es un punto importante en el entrenamiento del tenis de mesa. Debido a la elevada carga muscular, pueden producirse lesiones ocasionales durante la práctica de esta actividad, que requieren la intervención de un rehabilitador físico especializado. Objetivo Explorar el proceso de rehabilitación en las lesiones musculares causadas por el entrenamiento de alta intensidad en atletas de tenis de mesa. Métodos 31 estudiantes atletas de tenis de mesa con indicación de rehabilitación debido a lesiones musculares causadas por el entrenamiento de alta intensidad fueron voluntarios de esta investigación. Los datos pertinentes para la investigación se recogieron antes y después de la intervención. Se analizó la fuerza muscular, la prueba del tanque, la prueba de elevación, el par máximo del grupo de flexores y extensores a una velocidad de 60°/s y el par máximo del grupo de flexores y extensores a una velocidad de 60°/s, los datos se almacenaron y analizaron en un software estadístico. Los resultados fueron analizados y contrastados con la literatura científica actualizada. Resultados La investigación demuestra que un buen método de recuperación no sólo puede aliviar el dolor muscular y reducir los problemas psicológicos causados por el dolor, sino que también puede acelerar la ganancia de movimiento de las articulaciones. Conclusión El protocolo analizado en este trabajo puede mejorar el nivel deportivo de los atletas tanto desde el punto de vista fisiológico como psicológico, además de promover una recuperación más rápida, siendo apto para su aplicación práctica diaria. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

[Hydrodynamic characteristics of grass swale runoff in Guanzhong area of Loess Plateau, Northwest China.] / é»„åœŸé«˜åŽŸå ³ä¸­åœ°åŒºæ¤è‰æ²Ÿå¾„æµæ°´åŠ›å­¦ç‰¹æ€§.

Grass swale has been widely used in sponge city construction, which can effectively improve the urban ecological environment. To explore the regulation mechanism of runoff in grass swale, runoff scouring experiment was carried out to study the hydrodynamic characteristics of runoff and the distribution of cross-section velocity under the combined conditions of five slopes (1%, 2%, 3%, 4%, 5%) and five scour flows (20, 30, 40, 50, 60 L·min-1). With the increases of flow rate and slope, flow velocity, Reynolds number and Froude number all increased gradually, while the Manning roughness coefficient and Darcy-Weisbach friction coefficient decreased gradually. The velocity (V) could be expressed as a power function V=0.3387Q0.555S0.6601 of flow rate (Q) and slope (S). The variation ranges of Reynolds number and Froude number were 1160.95-6596.82 and 0.17-1.21, respectively. The runoff flow patterns were all turbulent. The flow pattern was greatly affected by the slope. When flow rate and slope were small, they had great influence on friction coefficient. Under the experimental conditions, the Darcy-Weisbach friction coefficient was negatively correlated with Reynolds number. The velocity distribution of cross-section showed symmetrical distribution on both sides of the center. The maximum velocity point was located at the center of water surface. With the increases of flow rate and slope, the velocity contours of cross section gradually became dense and the gradient of the velocity change increased. Our results provide a theoretical basis for the design, application and hydraulic calculation of grass swale in the construction of sponge cities in loess areas, and reveal the runoff regulation mechanism by analyzing the hydraulic characteristics of grass swale runoff.

GAN-Based Video Denoising with Attention Mechanism for Field-Applicable Pig Detection System.

Infrared cameras allow non-invasive and 24 h continuous monitoring. Thus, they are widely used in automatic pig monitoring, which is essential to maintain the profitability and sustainability of intensive pig farms. However, in practice, impurities such as insect secretions continuously pollute camera lenses. This causes problems with IR reflections, which can seriously affect pig detection performance. In this study, we propose a noise-robust, real-time pig detection system that can improve accuracy in pig farms where infrared cameras suffer from the IR reflection problem. The system consists of a data collector to collect infrared images, a preprocessor to transform noisy images into clean images, and a detector to detect pigs. The preprocessor embeds a multi-scale spatial attention module in U-net and generative adversarial network (GAN) models, enabling the model to pay more attention to the noisy area. The GAN model was trained on paired sets of clean data and data with simulated noise. It can operate in a real-time and end-to-end manner. Experimental results show that the proposed preprocessor was able to significantly improve the average precision of pig detection from 0.766 to 0.906, with an additional execution time of only 4.8 ms on a PC environment.

Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification.

PURPOSE: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis. METHODS: The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein-protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR. RESULTS: A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR. CONCLUSIONS: Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH.

Active targeted Janus nanoparticles enable anti-angiogenic drug combining chemotherapy agent to prevent postoperative hepatocellular carcinoma recurrence.

Surgery is one of the main effective strategies for the treatment of solid tumors, but high postoperative recurrence is also the main cause of death in current cancer therapy. The prevention of postoperative hepatocellular carcinoma (HCC) recurrence is a clinical problem that needs to be solved urgently. At present, there are still some problems to be solved, such as, how to achieve free drugs to target the site of surgical resection; develop a strategy for the simultaneous administration of multiple drugs to inhibit postoperative recurrence; and provide the appropriate animal model that mimics the process of postoperative HCC recurrence. In this study, we used a facile and reproducible method to successfully prepare amphiphilic Janus nanoparticles (JNPs). In order to improve targeting of the JNPs to residual HCC cells after surgery, we modified the side of gold nanorods (GNRs) with lactobionic acid (LA), thus creating LA-JNPs. This provided an active and targeted co-delivery system for hydrophilic and hydrophobic drugs in separate rooms, thus avoiding mutual effects. Next, we established two models to simulate postoperative HCC recurrence: a subcutaneous postoperative recurrence model based on patient-derived tumor xenograft (PDX) tissues and a postoperative recurrence model of orthotopic HCC. By applying these models, the enhanced permeability and retention effect (EPR) based tumor targeting and LA based active targeting can jointly promote the enrichment and uptake of JNPs at tumor site. LA-JNPs represented an efficient targeting system for the co-delivery of Sorafenib/Doxorubicin with an optimized anti-recurrence effect and significantly improved the survival of mice during treatment for postoperative recurrence.

The characterization, cytotoxicity, macrophage response and tissue regeneration of decellularized cartilage in costal cartilage defects.

After harvesting multiple costal cartilages, the local defect disrupts the integrity of the chest wall and may lead to obvious thoracic complications, such as local depression and asymmetry of the bilateral thoracic height. Decellularized materials have been used for tissue reconstruction in clinical surgeries. To apply xenogenic decellularized cartilage in costal cartilage defects, porcine-derived auricular and costal cartilage was tested for characterization, cytotoxicity, macrophage response, and tissue regeneration. Most of the DNA and α-Gal were effectively removed, and the collagen was well preserved after the decellularization process. The glycosaminoglycan (GAG) content decreased significantly compared to that in untreated cartilage. The decellularized auricular cartilage had a larger pore size, more pores, and a higher degradation rate than the decellularized costal cartilage. No apparent nuclei or structural damage was observed in the extracellular matrix. The decellularized auricular cartilage had a higher cell proliferation rate and more prominent immunomodulatory effect than the other groups. Two types of decellularized cartilage, particularly decellularized auricular cartilage, promoted the tissue regeneration in the cartilage defect area, combined with noticeable cartilage morphology and increased chondrogenic gene expression. In our research, the functional components and structure of the extracellular matrix were well preserved after the decellularization process. The decellularized cartilage had better biocompatibility and suitable microenvironment for tissue regeneration in the defect area, suggesting its potential application in cartilage repair during the surgery. STATEMENT OF SIGNIFICANCE: Autologous costal cartilage has been widely used in various surgeries, while the cartilage defects after the harvesting of multiple costal cartilages may cause localized chest wall deformities. Decellularized cartilage is an ideal material that could be produced in the factory and applied in surgeries. In this study, both decellularized costal cartilage and auricular cartilage preserved original structure, functional biocompatibility, immunosuppressive effects, and promoted tissue regeneration in the cartilage defect area.

Molecular mechanism of Wutou Decoction in the treatment of osteoarthritis: a bioinformatics and molecular docking study.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA. METHODS: The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated. RESULTS: Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA. CONCLUSIONS: WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1ß, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.

Simplified ARCHITECT microfluidic chip through a dual-flip strategy enables stable and versatile tumoroid formation combined with label-free quantitative proteomic analysis.

Recent years, microfluidic three-dimensional (3D) tumor culture technique has made great progress in tumor microenvironment simulation and drug screening. Meanwhile, as their functionality and complexity increase, it is more difficult for current chip models to selectively collect specific-layer cells from tumoroids for further analysis. Moreover, a simplified and robust method for tumoroid formation with highly consistent size and repeatable 3D morphology is relatively ncessary. Here, we report an ARCHITECT (ARtificial CHIp for Tumor Enables Confocal Topography observation) chip, through a dual-flip strategy to implement straightforward tumoroid establishment. This platform guarantees stable batch-to-batch tumoroids formation and allows high resolution confocal imaging. Moreover, an initial cell density as low as 65 cells per chamber is efficient to deliver a tumoroid. With this ARCHITECT chip, different-layer cells of interest could be collected from tumoroid for label-free quantitative (LFQ) proteomic analysis. For application demonstration, we mainly verified this platform for lung carcinoma (A549) tumoroid construction and proteomic analysis at out layer. Our data indicate that the out-layer cells of A549 tumoroid show extensively distinct proteomic expressions compared to two-dimensional cultured A549 cells. The up-regulated proteins are mainly related to tumorigenicity, proliferation and metastasis. And the differentially expressed proteins are mainly relevant to lipid metabolism pathway which is essential to tumor progression and proliferation. This platform provides a simplified yet robust technique to connect microfluidic tumoroid construction and LFQ proteomic analysis. The simplicity of this technique should open the way to numerous applications such as discovering the innovative targets for cancer treatment, and studying the mophological and proteomic heterogeneity of different-layer cells across the tumoroid.

Exploiting the Catalytic Ability of Polydopamine-Remodeling Gold Nanoparticles toward the Naked-Eye Detection of Cancer Cells at a Single-Cell Level.

In this study, a catalytic polydopamine-remodeling gold nanoparticle sensitized with an antinucleolin AS1411 probe (pAu nanoprobe) is synthesized, where the surface of the gold nanoparticles (AuNPs) is modified with a spontaneous self-polymerization of a polydopamine coating that imparts the probe functionalization ability and antispecific protein binding while the intrinsic catalytic property of the AuNPs is preserved. The functionalized AS1411 probe exerts specific recognition with nucleolin protein that is found to be overexpressed on the surface of breast cancer cells (MDA-MB-231). Scanning electron microscopy (SEM) confirms that the specific binding of the pAu nanoprobe occurs at the cancer cell surface. Taking advantage of the catalytic ability of the pAu nanoprobe in reducing blue-colored methylene blue (MB) to colorless leuco-MB, a colorimetric biosensing platform is established based on the accessible catalytic active sites on the pAu nanoprobe toward MB. The specific binding inhibits the pAu nanoprobe from efficiently catalyzing the reduction of MB, resulting in a "turn-off" catalytic biosensing platform. The catalytic conversion of MB is inversely proportional to the concentration of the nucleolin protein and the cancer cells, yielding a detection limit of 15 pM of the nucleolin protein and two cancer cells. The presence of five orders of magnitude higher concentration of bovine serum albumin hardly affects the catalytic ability of the pAu nanoprobe, that is, 88% catalytic ability is still preserved, which validates the specificity of the proposed pAu nanoprobe. In particular, a distinct color contrast creates a significant signal-to-noise ratio so as to enable single-cell level detection of two cancer cells by naked-eye judgment. Moreover, the undiluted, real human serum samples spiked with the cancer cells were examined with an impressive recovery of 94 ± 0.3%, which holds great promise in cancer cell screening.

Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation.

Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.

A rare case of giant retroperitoneal neurilemmoma.

Neurilemmoma, also known as schwannoma or neurinoma, is a tumor that originates from neural sheath Schwann cells. Giant neurilemmomas derived from the retroperitoneum have rarely been reported. We herein describe a woman with a giant retroperitoneal neurilemmoma that was initially incorrectly diagnosed as an inflammatory abdominal mass. The tumor extended from the patient's hypogastrium to her pelvic cavity and measured 20 × 15 × 10 cm. The tumor was excised via laparotomy and diagnosed as a retroperitoneal neurilemmoma through histological and immunohistochemical examination. Although rare, particularly in the giant form, neurilemmoma should be considered as an important differential diagnosis in patients with a retroperitoneal tumor or inflammatory abdominal mass. Complete excision should be considered for the potential cure of giant retroperitoneal neurilemmomas.

Nuclear import of LIKE HETEROCHROMATIN PROTEIN1 is redundantly mediated by importins α-1, α-2 and α-3.

LIKE HETEROCHROMATIN PROTEIN1 (LHP1) encodes the only plant homologue of the metazoan HETEROCHROMATIN PROTEIN1 (HP1) protein family. The LHP1 protein is necessary for proper epigenetic regulation of a range of developmental processes in plants. LHP1 is a transcriptional repressor of flowering-related genes, such as FLOWERING LOCUS T (FT), FLOWERING LOCUS C (FLC), AGAMOUS (AG) and APETALA 3 (AP3). We found that LHP1 interacts with importin α-1 (IMPα-1), importin α-2 (IMPα-2) and importin α-3 (IMPα-3) both in vitro and in vivo. A genetic approach revealed that triple mutation of impα-1, impα-2 and impα-3 resulted in Arabidopsis plants with a rapid flowering phenotype similar to that of plants with mutations in lhp1 due to the upregulation of FT expression. Nuclear targeting of LHP1 was severely impaired in the impα triple mutant, resulting in the de-repression of LHP1 target genes AG, AP3 and SHATTERPROOF 1 as well as FT. Therefore, the importin proteins IMPα-1, -2 and -3 are necessary for the nuclear import of LHP1.

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells.

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

Study on the molecular mechanism of BuShenHuoXue capsule in treatment of steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is the pathological process caused by the death of the active components of the head of the femur due to the high dose of hormones, which has become a common public health problem. BuShenHuoXue capsule (BSHXC) has been clinically proven to be effective against the SONFH, the main pharmacological action of BSHXC is tonifying kidney and promoting blood circulation, but the mechanism remains to be explored. METHODS: We established a rat SONFH model by injecting Methylprednisolone (MPS) into the right gluteus muscle 30 mg/kg/d, 3 days of continuous injection every week, 4 weeks in total. According to the clinical dosage of BSHXC (Herba epimedium 3 g, Eucommia ulmoides 15 g, Salvia miltiorrhizae 30 g, Chuanxiong 15 g, Paeonia lactiflora Pall 15 g, Poria cocos 12 g, Achyranthes bidentata 12 g, antler gum 10 g, Cyperus rotundus L. Nine g and Radix Glycyrrhizae 9 g), it was converted into the equivalent dose of rats, and gavage was performed at the weight of 10 mL/kg, once per day. The BSHXC was subjected to experiments in vivo, SONFH pharmacodynamics, bioinformatics, and network of pharmacology to determine the active ingredients, and its protective role against SONFH, Enrichment analysis was performed to explore the possible mechanism of BSHXC, and cell experiments were undertaken to analyze the impact of BSHXC on the hormones associated with bone marrow mesenchymal stem cells (BMSCs) between osteogenesis and apoptosis. RESULTS: Experiments confirmed that BSHXC could effectively reduce bone loss in SONFH rat models. From bioinformatics and a network constructed from 10 drugs-208 pharmacology-126 targets, the enrichment analysis showed that the core targets were inflammatory reaction, steroid hormones, estrogen receptors, osteoporosis, and adjustment of osteogenesis and osteoclast differentiation, among others. The cell proliferation and staining supported that the mechanism of BSHXC promoted osteogenesis and intervening in apoptosis. CONCLUSIONS: The BSHXC reduced the inflammatory response, changed steroid response, regulated estrogen receptors, delayed osteoporosis, regulated osteoblast and osteoclast differentiation by regulating related targets, and improved the local microenvironment by a multi-component, multi-target, and multi-link process to delay or reverse the progression of SONFH.

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain.

PURPOSE: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). METHODS: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. RESULTS: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). CONCLUSION: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

Abstract Purpose: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). Methods: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. Results: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). Conclusion: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

MiR-34a-5p mediates sevoflurane preconditioning induced inhibition of hypoxia/reoxygenation injury through STX1A in cardiomyocytes.

Anesthetic preconditioning is a cellular protective approach whereby exposure to a volatile anesthetic renders cardio injury. Sevoflurane preconditioning has been shown to exhibit cardio protective effect on hypoxia/reoxygenation (H/R) injury, but the underlying mechanism is unclear. Syntaxin 1A (STX1A), an important regulator in cardio disease, was predicted to be the target gene of microRNA-34a-5p (miR-34a-5p). The current research was designed to delineate the role of miR-34a-5p in regulating sevoflurane preconditioning in cardiomyocytes injury. In this study, the results demonstrated that the expression of STX1A was significantly increased, while miR-34a-5p was dramatically decreased in sev-preconditioning H9c2 cells as compared with cells only under H/R stimulation. Moreover, miR-34a-5p regulated the protective effect of sev-preconditioning in injured H9c2 cells by mediating cell proliferation and cell apoptosis. Additionally, the luciferase report confirmed the targeting reaction between STX1A and miR-34a-5p. Taken together, our study suggested that miR-34a-5p regulated sev-preconditioning induced inhibition of hypoxia/reoxygenation injury through mediating STX1A, provided a potential therapeutic target for anesthetic protection in cardio disease.