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Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.
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Proteínas Sanguíneas , Densidad Ósea , Análisis de la Aleatorización Mendeliana , Simulación del Acoplamiento Molecular , Osteoporosis , Humanos , Osteoporosis/fisiopatología , Osteoporosis/tratamiento farmacológico , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Densidad Ósea/fisiología , Densidad Ósea/efectos de los fármacos , Mapas de Interacción de Proteínas , Terapia Molecular Dirigida/métodos , Estudio de Asociación del Genoma Completo , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacologíaRESUMEN
BACKGROUND: To evaluate the reliability of the Soft Tissue Tension Cloud Chart (STTCC) technology, an original method combining multi-point Cervical Paravertebral Soft Tissue Test (CPSTT) with MATLAB software, we conducted a preliminary analysis on the immediate effects of Orthopaedic Manual Therapy (OMT) on cervical paravertebral soft tissue. METHODS: 30 patients with Cervical Spondylotic Radiculopathy (CSR) were included in this study. We analyzed the differences in CPSTT before and after treatment with Cervical Rotation-Traction Manipulation (CRTM), a representative OMT technique in Traditional Chinese Medicine, using the STTCC technology. RESULTS: The STTCC results demonstrated that post-treatment CPSTT levels in CSR patients were significantly lower than pre-treatment levels after application of CRTM, with a statistically significant difference (P < 0.001). Additionally, pre-treatment CPSTT levels on the symptomatic side (with radicular pain or numbness) were higher across the C5 to C7 vertebrae compared to the asymptomatic side (without symptoms) (P < 0.001). However, this difference disappeared after CRTM treatment (P = 0.231). CONCLUSIONS: The STTCC technology represents a reliable method for analyzing the immediate effects of OMT. CSR patients display uneven distribution of CPSTT characterized by higher tension on the symptomatic side. CRTM not only reduces overall cervical soft tissue tension in CSR patients, but can also balance the asymmetrical tension between the symptomatic and asymptomatic sides. TRIAL REGISTRATION: This study was approved by the Chinese Clinical Trials Registry (Website: . https://www.chictr.org.cn .) on 20/04/2021 and the Registration Number is ChiCTR2100045648.
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Manipulación Espinal , Radiculopatía , Espondilosis , Humanos , Rotación , Tracción/métodos , Reproducibilidad de los Resultados , Manipulación Espinal/métodos , Vértebras Cervicales , Radiculopatía/diagnóstico , Radiculopatía/terapia , Espondilosis/terapia , TecnologíaRESUMEN
With the rapid advancement of drone technology and the growing applications in the field of drone engineering, the demand for precise and efficient path planning in complex and dynamic environments has become increasingly important. Traditional algorithms struggle with complex terrain, obstacles, and weather changes, often falling into local optima. This study introduces an Improved Crown Porcupine Optimizer (ICPO) for drone path planning, which enables drones to better avoid obstacles, optimize flight paths, and reduce energy consumption. Inspired by porcupines' defense mechanisms, a visuo-auditory synergy perspective is adopted, improving early convergence by balancing visual and auditory defenses. The study also employs a good point set population initialization strategy to enhance diversity and eliminates the traditional population reduction mechanism. To avoid local optima in later stages, a novel periodic retreat strategy inspired by porcupines' precise defenses is introduced for better position updates. Analysis on the IEEE CEC2022 test set shows that ICPO almost reaches the optimal value, demonstrating robustness and stability. In complex mountainous terrain, ICPO achieved optimal values of 778.1775 and 954.0118; in urban terrain, 366.2789 and 910.1682 and ranked first among the compared algorithms, proving its effectiveness and reliability in drone delivery path planning. Looking ahead, the ICPO will provide greater efficiency and safety for drone path planning in navigating complex environments.
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Algoritmos , Puercoespines , Animales , Robótica/métodos , AmbienteRESUMEN
Background: Manual therapy has been used as an alternative approach to treat knee osteoarthritis (KOA) for many years. Numerous systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its effectiveness and safety. Nevertheless, the conclusions of SRs/MAs are inconsistent, and the uneven quality needs to be critically appraised. Objectives: To conduct a comprehensive overview of the effectiveness and safety of manual therapy for KOA and the quality of relevant SRs/MAs, thus providing critical evidence and valuable direction for future researchers to promote the generation of advanced evidence. Methods: The pre-defined search strategies were applied to eight electronic databases from inception to September 2022. Suitable SRs/MAs were included in accordance with the inclusion and exclusion criteria. The methodological quality, risk of bias, reporting quality, and evidence quality were assessed by two independent reviewers who used respectively the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 Version (PRISMA 2020), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE) based on the method of narrative synthesis. We excluded the overlapping randomized controlled trials (RCTs) and performed a re-meta-analysis of the total effective rate. Results: A total of eleven relevant SRs/MAs were included: nine SRs/MAs were rated critically low quality, and two were rated low quality by AMSTAR-2. According to ROBIS, all SRs/MAs were rated low risk in Phase 1 (assessing relevance) and Domain 1 (study eligibility criteria) of Phase 2. Three SRs/MAs (27.27%) were rated low risk in Domain 2 (identification and selection of studies). Ten SRs/MAs (90.91%) were rated low risk in Domain 3 (data collection and study appraisal). Five SRs/MAs (45.45%) were rated low risk in Domain 4 (synthesis and findings). And five SRs/MAs (45.45%) were rated low risk in Phase 3 (risk of bias in the review). By PRISMA 2020, there were some reporting deficiencies in the aspects of abstract (2/11, 18.18%), search strategy (0/11, 0%), preprocessing of merging data (0/11, 0%), heterogeneity exploration (6/11, 54.55%), sensitivity analysis (4/11, 36.36%), publication bias (5/11, 45.45%), evidence quality (3/11, 27.27%), the list of excluded references (3/11, 27.27%), protocol and registration (1/11, 9.09%), funding (1/11, 9.09%), conflict of interest (3/11, 27.27%), and approach to relevant information (0/11, 0%). In GRADE, the evidence quality was defined as moderate quality (8 items, 21.05%), low quality (16 items, 42.11%), and critically low quality (14 items, 36.84%). Among the downgraded factors, risk of bias, inconsistency, imprecision, and publication bias were the main factors. A re-meta-analysis revealed that manual therapy can increase the total effective rate in KOA patients (risk ratio = 1.15, 95% confidence interval [1.12, 1.18], p < 0.00001; I2 = 0, p = 0.84). There are four reviews that narratively report adverse effects, and no severe adverse reactions occurred in the manual therapy group. Conclusions: Manual therapy may be clinically effective and safe for patients with KOA. However, this conclusion must be interpreted with caution because of the generally unsatisfactory study quality and inconsistent conclusions of the included SRs/MAs. Further rigorous and normative SRs/MAs are expected to be carried out to provide robust evidence for definitive conclusions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier: CRD42022364672.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/terapia , Proyectos de Investigación , Informe de Investigación , SesgoRESUMEN
Purpose: Baduanjin (BDJ) exercise is a traditional exercise that combines breathing, body movement, meditation and awareness to help delay the onset and progression of senile degenerative musculoskeletal diseases, such as osteoporosis (OP). The aim of this meta-analysis is to evaluate the efficacy of BDJ exercise, and preliminarily infer its effective mechanism in the treatment of OP. Methods: We identified relevant randomized controlled trials (RCTs) through eight databases, and compared BDJ exercise with the control groups (including blank control and conventional treatment intervention). The main outcome measure was bone mineral density (BMD), the additional outcome measures were visual analogue scale (VAS), Berg balance scale (BBS), serum Calcium (Ca), serum Phosphorus (P), serum Alkaline phosphatase (ALP), and serum bone gla protein (BGP). Meta-analysis and trial sequence analysis (TSA) were performed using RevMan 5.4, Stata 16.0, and TSA 0.9. Results: In total, 13 RCTs involving 919 patients were included in the analysis. For postmenopausal osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine. BDJ exercise alone can influence serum Ca and ALP. BDJ exercise combined with conventional treatment can improve balance (BBS) and influence serum BGP. For senile osteoporosis, BDJ exercise alone and BDJ exercise combined with conventional treatment can improve balance (BBS). BDJ exercise combined with conventional treatment can improve the BMD of hip and pain relieve (VAS). For primary osteoporosis, BDJ exercise combined with conventional treatment can improve the BMD of lumbar spine and femoral neck. Conclusion: Baduanjin exercise may be beneficial to improve BMD, relieve pain, improve balance ability, influence serum BGP and serum ALP in patients with OP, but differences occur due to various types of OP. Due to the low quality of research on the efficacy and mechanism of BDJ exercise in the treatment of OP, high-quality evidence-based research is still needed to provide reliable supporting evidence. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022329022].
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Through collecting the relevant provisions and medical cases of wei syndrome treated with acupuncture and moxibustion from ancient medical works, the diagnosis and acupoint selection in treatment of generalized myasthenia gravis (gMC) with acupuncture and moxibustion were analyzed systematically from 3 aspects, i.e. meridian differentiation, disease differentiation and syndrome differentiation. In treatment based on meridian differentiation, the acupoints are selected in the light of the running course of meridian and characteristics of meridian disorders. In treatment based on disease differentiation, the acupoints are selected in accordance with etiology, pathogenesis and transmission stages of wei syndrome. Concerning to syndrome differentiation in treatment, the acupoints are selected on the basis of therapeutic principles determined by different syndromes/patterns of wei syndrome. In modern clinical practice, the treatment for gMC should be rooted at ancient literature, thus a standardized regimen can be developed for diagnosis and treatment with acupuncture and moxibustion.