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PURPOSE: To evaluate the Efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) versus Hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA). METHODS: Eligible randomized controlled trials (RCTs) were identified through a search of Pubmed, Embase, the Cochrane Library, Web of science, SinoMed and CNKI databases from inception to March 2024. For meta-analysis, data on clinical outcomes were measured using a visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); data on safety was evaluated by the incidence of adverse events. Two researchers independently read the included literatures, extracted data and evaluated the quality, and used Cochrane risk bias assessment tool for bias risk assessment, and RevMan5.3 software for Meta-analysis. RESULT: Ten RCTs involving 818 patients with KOA ranging from I-â ¢ Kellgren - Lawrence grading scale were included in this meta-analysis. Meta results showed that compared with the HA control group, at 12months, the WOMAC total score ï¼»MD=-10.22, 95% CI (-14.86â¼-5.59), P<0.0001, Z=4.32ï¼½;VAS scoreï¼»MD=-1.31, 95% CI (-1.90â¼-0.73), P<0.0001, Z=4.40ï¼½; WORMS score ï¼»MD=-26.01,95% CI ï¼-31.88â¼-20.14ï¼,P<0.001,Z=8.69ï¼½of MSCs group all decreased significantly (P<0.05), and reached the minimum clinically important differences (MCID). Furthermore, there was no significant difference in the incidence of adverse events (RR=1.54, 95% CI= 0.85 â¼ 2.79, P=0.16, I2=0) between the two groups (P >0.05). CONCLUSION: Compared to HA, intra-articular injection of MSCs therapy appears to effectively alleviate joint pain, improve clinical function of KOA patients. These benefits are observed to last for at least 12 months without an increase in adverse events. Due to limited, varied, and lacking MCID results in existing literatureï¼further research is needed. LEVEL OF EVIDENCE: Level I, Meta-analysis of Level I studies.
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Background and purpose: Surgical indications for Bernese periacetabular osteotomy (PAO) are well-established. However, the extent of postoperative functional recovery varies widely, as observed in clinical follow-ups. Thus, preoperative evaluation is crucial. This study aims to identify factors that influence functional recovery post-PAO and to develop a predictive nomogram. Patients and methods: Retrospective data were collected between December 2016 and March 2022 at The First Affiliated Hospital of Shandong First Medical University. The dataset included demographic and imaging data of patients who underwent PAO. The least absolute shrinkage and selection operator (LASSO) regression was utilized to identify influencing factors, which were further analyzed using multivariate logistic regression to construct a predictive nomogram for post-PAO functional recovery. Result: The analysis identified critical factors affecting functional recovery post-PAO, namely, the preoperative distance from the innermost surface of the femoral head to the ilioischial line, the surgical approach, preoperative acetabular depth, and the continuity of the preoperative Calve line. A nomogram was developed using these significant predictors. The model's validity was demonstrated by the receiver operating characteristic curve, with an area under the curve of 0.864. Additionally, the calibration curve confirmed the nomogram's accuracy, showing a strong correlation between observed and predicted probabilities, indicating high predictive accuracy. Conclusion: This predictive nomogram effectively identifies patients most suitable for PAO, providing valuable guidance for selecting surgical candidates and determining the appropriate surgical approach.
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OBJECTIVE: A robotic system was recently introduced to improve prosthetic alignment during total knee arthroplasty (TKA). The purpose of this multicenter, prospective, randomized controlled trial (RCT) was to determine whether robotic-arm-assisted TKA improves clinical and radiological outcomes when compared to conventional TKA. METHODS: One hundred and thirty patients who underwent primary TKA were enrolled in this prospective, randomized controlled trial, which was conducted at three hospitals. Five patients were lost to follow-up 6 weeks after surgery. Therefore, 125 participants (63 in the intervention group and 62 in the control group) remained in the final analysis. The primary outcome was the rate at which the mechanical axis of the femur deviated by less than 3° from the mechanical axis of the tibia. This was evaluated by full-length weight-bearing X-rays of the lower limb 6 weeks postoperatively. Secondary outcomes included operation times, 6-week postoperative functional outcomes evaluated by the American Knee Society score (KSS) and the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), short form-36 (SF-36) health survey results, and the occurrence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: At 6 weeks postoperatively, we found that the rate of radiographic inliers was significantly higher in the intervention group (78.7% vs 51.6%; p = 0.00; 95% confidence interval, 10.9% to 43.2%). The operation was significantly longer in the intervention group than in the control group (119.5 vs 85.0 min; p = 0.00). There were no significant differences in the 6-week postoperative functional outcomes, SF-36, AEs, and SAEs between the two groups. There were no AEs or SAEs that were determined to be "positively related" to the robotic system. CONCLUSION: Robotic-arm-assisted TKA is safe and effective, as demonstrated in this trial.
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Few of single-atom materials have been served as platform to analyze small molecules for surface assisted laser desorption/ionization mass spectrometry (SALDI-MS). Herein, a novel single Co atom-anchored MXene (Co-N-Ti3C2) is prepared to achieve enhanced SALDI-MS and mass spectrometry imaging (MSI) performance for the first time. The Co-N-Ti3C2 films were prepared by a simple in situ self-assembly strategy to generate an efficient SALDI-MS platform. Compared to typical inorganic/organic matrices, Co-N-Ti3C2 films exhibit superior performance in small molecules detection with ultra-high sensitivity (LOD at amol level), excellent repeatability (CV <4%), clean background and wide analyte coverage, enabling accurate quantitative analysis of various low-concentration metabolites from 1 µL biofluid in seconds. Its usage efficiently enhanced SALDI-MS detection of various small-molecule biomarkers such as amino acids, succinic acid, itaconic acid, arachidonic acid, citrulline, prostaglandin E2, creatinine, uric acid, glutamine, D-mannose, cholesterol and inositol in positive ion mode. The blood glucose level in humans was successfully determined from a linearity concentration range (0.25-10 mM). Notably, the Co-N-Ti3C2 assisted SALDI-MSI enables study the spatial distribution of small molecules covering the range central to metabolomics at a high resolution on a tissue section. Furthermore, Co-N-Ti3C2 platform revealed a speciï¬c peak proï¬le that distinguishes osteoarthritis (OA) from rheumatoid arthritis (RA) tissue. Density functional theory theoretical investigation revealed that single Co atoms anchored on Ti3C2 could highly enhanced the ionization ability of metabolites, resulting in high-sensitivity and heterogeneous metabolome coverage.
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Técnicas Biosensibles , Cobalto , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Aim: The objective was to investigate the association of periodontitis and tooth loss with extent of diabetic coronary atherosclerosis. Materials and methods: 272 patients who were hospitalized at Shanghai East hospital and underwent a coronary artery calcium (CAC) CT scan were enrolled in this study. Individuals were grouped based on their CAC scores into a normal-to-mild coronary atherosclerosis (AS) group (0 ≤ score ≤ 100, n=184) and a moderate-to-severe group (score≥101, n=88). Periodontitis parameters and number of missing teeth were evaluated for every patient. The severity of periodontitis was categorized as mild, moderate, or severe. The taxonomic composition of the microbiota was determined using full-length 16S ribosomal RNA gene sequencing. Salivary inflammatory factors were tested by ELISA. Results: Clinical attachment loss (CAL) (P =0.05) and the number of teeth lost (P = 0.016) were significantly higher in the moderate-to-severe coronary AS group, with these differences being more obvious in younger patients and patients with short-duration diabetes. Multivariate logistic regression analysis revealed that CAL (OR = 1.231, 95% CI = 1.066-1.214, P = 0.047) and having 10-19 missing teeth (OR = 1.604, 95% CI = 1.393-6.555, P = 0.05) were strongly associated with the presence of moderate-to-severe coronary AS. Salivary IL-6 and TNF-α levels, as well as levels of Porphyromonas gingivalis and Neisseria mucosa, were significantly elevated in the moderate-to-severe coronary AS group. Conclusion: It was found that both tooth loss and CAL were related to the extent of diabetic coronary AS. Saliva inflammatory factors and oral bacteremia may be new biomarkers for moderate-to-severe coronary AS.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Periodontitis , Pérdida de Diente , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Pérdida de Diente/complicaciones , China , Periodontitis/complicacionesRESUMEN
Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic effect of Methazolamide in Ankylosing spondylitis (AS). In this study, we explored the pathogenic role of CA1 and the pharmacological mechanism of Methazolamide in AS through Gene Set Enrichment Analysis (GSEA) and network pharmacology. Seven out of twelve CA1 related gene sets were enriched in AS group. CA1 was core enriched in above seven gene sets involving zinc ion binding, arylesterase activity and one carbon metabolic process. Functional analysis of the candidate target genes obtained from the intersection of AS associated genes and Methazolamide target genes indicated that Methazolamide exerts therapeutic effects on AS mainly through inflammatory pathways which regulate the production of tumor necrosis factor, IL-6 and nitric oxide. PTGS2, ESR1, GSK3ß, JAK2, NOS2 and CA1 were selected as therapeutic targets of Methazolamide in AS. Molecular docking and molecular dynamics simulations were performed successfully. In addition, we innovatively obtained the intersection of Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and GSEA results, and found that 18 GO terms and 5 KEGG terms were indicated in the pharmacological mechanism of Methazolamide in AS, involving bone mineralization, angiogenesis, inflammation, and chemokine signaling pathways. Nevertheless, validation for these mechanisms is needed in vivo/vitro experiments.
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Metazolamida , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Farmacología en Red , Simulación del Acoplamiento Molecular , Inhibidores de Anhidrasa CarbónicaRESUMEN
Knee osteoarthritis (KOA) is a chronic joint disease characterized by the degeneration of articular cartilage. In this study, we explored the potential therapeutic effects of platelet-rich plasma (PRP) and identified molecular targets for treating KOA. A rat model of KOA was established via the Hulth method and primary knee joint chondrocytes were isolated to evaluate the effects of PRP and shRNA targeting p65 (sh-p65). ELISA was used to detect inflammatory factors, including IL-6, IL-1ß, and TNF-α. HE staining, Safranin O/Fast Green staining and Masson staining were performed to evaluate the morphology of articular cartilage, followed by detection of p65, COL2A1, ACAN, MMP13, and ADAMTS5 expression. The proliferation and apoptosis of primary knee chondrocytes were detected by the CCK-8 assay and TUNEL staining, respectively. Treatment with either PRP or sh-p65 decreased IL-6, IL-1ß, and TNF-α levels in the peripheral blood of KOA rats and chondrocyte culture supernatants, increased COL2A1 and ACAN levels, and decreased MMP13 and ADAMTS5 expression. Furthermore, administration of PRP or sh-p65 exerted protective effects on articular cartilage, enhanced the vitality of knee joint chondrocytes, and inhibited apoptosis. Collectively, PRP inhibited inflammation, promoted chondrocyte proliferation and cartilage matrix secretion, and induced cartilage regeneration by suppressing p65 expression; these effects allow PRP to alleviate KOA progression. P65-based targeted therapy administered in combination with PRP might be a promising strategy for treating KOA.
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Objective: To introduce a surgical technique (the "Y" line technique) that will control leg length discrepancy (LLD) after total hip arthroplasty and to observe its effectiveness and influencing factors. Methods: According to the inclusion and exclusion criteria, a total of 350 patients were selected in this study; 134 patients in whom used the "Y" line technique was used to control lower limb length were included in Group A and 166 patients treated with freehand methods to control lower limb length were included in Group B. A total of 50 patients in whom the standard anteroposterior x-ray of bilateral hips was taken preoperatively and in whom the "Y" line technique was used during the operation were included in Group C. Results: The postoperative LLD of Group A was 4.74â mm (3.93), that of Group B was 5.85â mm (4.60), and that of Group C was 2â mm (1.00)-the difference was statistically significant (p < 0.001). There were significant statistical differences when comparisons were made between any two groups (p < 0.01). The distribution of postoperative LLD in Group A was better than that in Group B, and this factor was better in Group C than in Group A-the difference was statistically significant (p < 0.001). Severe unequal length rates of the lower extremities (LLD > 10â mm) were 5.97% (8/134) in Group A, 14.3% (24/166) in Group B, and 0% (0/50) in Group C-the difference was statistically significant (p < 0.001). There were significant differences between Group A and Group B and between Group B and Group C (p < 0.05), but there was no significant difference between Group A and Group C (p = 0.078). Conclusion: The "Y" line technique, which does not increase the operating time and patient cost, can effectively reduce postoperative LLD. Insufficient internal rotation of the healthy lower extremity and the low projection position in the preoperative anteroposterior x-ray of the bilateral hips were important factors affecting the accuracy of the "Y" line technique.
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Introduction: The construction of the Yangtze River Delta ecological green development demonstration area aims to take the lead in exploring an eco-friendly development model, demonstrating and leading the higher quality integrated development of the Yangtze River Delta in China. Methods: Through literature research, expert inquiries, and policy documents as the guidance, this study builds an ecological green high-quality development evaluation system for the demonstration area, including building an index system composed of 4 first-class indicators, 16 second-class indicators and 42 third-class indicators derived from economy, society and environment system, determining the index weight through the network analytic hierarchy process, and establishing the comprehensive evaluation index (CEI) and differential diagnosis index (DDI) of high-quality development, which is based on the relevant theory of statistical comprehensive index. Results: The establishment of this system provides a complete theoretical support and scientific guidance for the comprehensive evaluation of high-quality ecological green development and more balanced development of the demonstration area; and it can point out the development direction for the subsequent development of the Yangtze River Delta. Discussion: However, due to the availability of data, there is still room for further improvement in this paper. In the future research, the model can be used to evaluate the high-quality development level of the demonstration area through the relevant data of the demonstration area.
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Ecosistema , Ríos , China , PredicciónRESUMEN
Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.
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Diabetes Mellitus Experimental , Animales , Ratones , Diabetes Mellitus Experimental/metabolismo , Mitocondrias/metabolismo , Ácido Láctico/metabolismo , MamíferosRESUMEN
Promoting green consumption is key in meeting ambitious sustainable fashion targets being set around the world. This research examined how framing of green message as positive or negative (i.e., benefit framing) influenced formation of sustainable consumption behaviors of fashion (SCBF) based on the cross-theoretical model and, especially, how self-efficacy, decision balancing, and perceiving threats-mediated green message framing effects. Data were collected from 217 Chinese residents in an online experiment. Our findings show that green message framing has different effects on individuals in different change stages of SCBF and loss framing-based green messages induce more positive responses toward SCBF with greater perceived threats in the pre-intention and intention stages, while gain framing-based green messages might stimulate positive behaviors toward SCBF with greater perceived benefits in the preparation and action and maintenance stages. Results suggest that highlighting green message expression in relating to SCBF may be useful for promoting broader sustainable behaviors. Therefore, this article significantly fills the gaps between green message framing and SCBF. The findings of this article have significant implications for fashion companies who wish to explore the fashion green market potential.
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Conductas Relacionadas con la Salud , Intención , Humanos , Modelos TeóricosRESUMEN
AIMS: The aim of this study was to evaluate the association between circulating oxLDL/LDL-C ratio and the severity of coronary atherosclerosis, along with other emerging biomarkers of cardiovascular disease (CVD) in patients with type 2 diabetes. METHODS: We recruited 152 patients with type 2 diabetes for our study. ELISA measured the plasma levels of oxLDL and other biomarkers. The severity of coronary lesions was evaluated using Gensini scores, which were calculated based on results of coronary computed tomographic angiography (CCTA). All patients were allocated into four groups according to CCTA findings and Gensini score: normal group (score = 0), mild coronary atherosclerosis group (0 < scores ≤ 3), moderate coronary atherosclerosis group (3.01 ≤ scores ≤ 32.67) and severe coronary atherosclerosis group (32.68 ≤ scores ≤ 180). Association between the oxLDL/LDL-C ratio and the severity of coronary atherosclerosis were evaluated using logistic regression models. RESULTS: Multivariate logistic regression analysis showed that the oxLDL/LDL-C ratio was positively associated with severity of coronary atherosclerosis (OR 2.03, 95% CI 1.31-3.14, p < 0.01). Interleukin 33 (IL33) correlated positively with oxLDL/LDL-C ratio (r = 0.274, p < 0.01). However, vascular cell adhesion molecular-1 (VCAM-1) had similar trends with oxLDL/LDL-C ratio in these 4 groups. CONCLUSIONS: OxLDL/LDL-C ratio is considered as a potential biomarker in patients with diabetes for early recognition and intervention of severe coronary atherosclerosis, and will be more effective if tested IL33 and VCAM-1 at the same time.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Biomarcadores , LDL-Colesterol , Enfermedad de la Arteria Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Interleucina-33 , Lipoproteínas LDL , Molécula 1 de Adhesión Celular VascularRESUMEN
AIMS/INTRODUCTION: Diabetic peripheral neuropathy is a common diabetes-related microvascular complication. The relationship between peripheral nerve function and glucose variability is unclear. We investigated the association of glucose variability with subclinical diabetic polyneuropathy in a large-scale sample of patients with type 2 diabetes. MATERIALS AND METHODS: We enrolled 509 individuals with type 2 diabetes who were screened for diabetic peripheral neuropathy and monitored using a continuous glucose monitoring system. Multiple glycemic variability parameters, including the mean amplitude of glycemic excursions, glucose standard deviation (SDgluc ) and glucose coefficient of variation were calculated from 3-day glucose profiles obtained from continuous glucose monitoring. All participants underwent nerve conduction studies, and the composite Z-scores for nerve conduction parameters were calculated. RESULTS: Multivariate logistic regression analyses showed that SDgluc and the conventional risk factor hemoglobin A1c (HbA1c) were independently associated with abnormal nerve function, and the corresponding odds ratios (95% confidence interval) were 1.198 (1.027-1.397, SDgluc ) and 1.182 (1.061-1.316, HbA1c), respectively. The composite Z-score of nerve conduction velocity and response amplitude obviously decreased with greater SDgluc , and the composite Z-score of distal latency significantly increased with increasing tertiles of SDgluc (all P trend <0.05). After adjusting for age, sex, body mass index, diabetes duration and HbA1c, SDgluc was independently associated with nerve conduction velocity (ß = -0.124, P = 0.021). CONCLUSIONS: The SDgluc is a significant independent contributor to subclinical diabetic polyneuropathy, in addition to conventional risk factors including diabetes duration and HbA1c.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Glucosa , Hemoglobina Glucada/análisis , HumanosRESUMEN
OBJECTIVE: To explore the influencing factors of age at onset of pain and severe pain in patients with Hartofilakidis type I developmental dysplasia of the hip (DDH). METHODS: A retrospective study of 83 patients with DDH treated at our hospital from January 2017 to June 2021 was conducted. The age at onset of pain, patients' demographic data, and radiographic parameters were collected. Multiple linear regression was used to determine the influencing factors of age at onset of pain. Cox regression analysis was used to determine the influencing factors of severe pain attacks. RESULTS: According to the results of multiple linear regression analysis, when the distance between the medial femoral head and the ilioischial line increased by one millimetre, the age at onset of pain decreased by 1.7 years (ß = - 1.738, 95% CI - 1.914-[- 1.561], p < 0.001). When the sharp angle increases by one degree, the age at onset of pain decreases by 0.3 years (ß = - 0.334, 95% CI - 0.496-[- 0.171], p < 0.001). According to the results of the Cox regression analysis, for each additional degree of the lateral centre-edge angle (LCEA), the probability of severe pain was reduced by 5% (Exp [ß]: = 0.947, 95% CI 0.898-0.999, p = 0.044). For each additional millimetre in the distance between the medial femoral head and the ilioischial line, the likelihood of severe pain increased by 2.4 times (Exp [ß]: 2.417, 95% CI 1.653-3.533, p < 0.001). CONCLUSION: Larger distances between the medial femoral head and the ilioischial line and sharp angle can lead to an earlier age at onset of pain in patients with DDH. Small LCEA and excessive distance between the medial femoral head and the ilioischial line are risk factors for severe pain.
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Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Acetábulo , Luxación Congénita de la Cadera/complicaciones , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/epidemiología , Articulación de la Cadera , Humanos , Osteotomía , Dolor/epidemiología , Dolor/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To explore factors affecting the efficacy of Bernese periacetabular osteotomy for the treatment of hip dysplasia. METHODS: A retrospective study was conducted on 44 patients with hip dysplasia who underwent Bernese periacetabular osteotomy with a modified Smith-Peterson approach between January 2017 and November 2019. Among them, 40 were women and four were men. The average age was 31.2 ± 9.4. Preoperative and postoperative imaging parameters were measured. The acetabular top tilt angle, lateral central edge angle, acetabular abduction angle, femoral head extrusion index, sphericity index of femoral head, Shenton line, Tonnis grade of osteoarthritis, joint congruency, p/a ratio, acetabular anteversion angle, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale scores, and modified Harris hip score (MHHS) were observed. MHHS were divided into three clinically relevant categories: poor (<70 points), good (70-85 points), and excellent (86-91 points). Patient demographic data, as well as preoperative and postoperative radiographic parameters, were subjected to univariate logistic regression analysis. Multiple regression analysis was used to determine factors influencing postoperative MHHS. RESULTS: The follow-up time was 1.0-3.9 years after surgery, with an average of 1.6 years. By the last follow-up, MHHS increased from 70 points before surgery to 91 points after surgery (P < 0.001), WOMAC pain score decreased from 4 points before surgery to 0 points after surgery (P < 0.001). WOMAC functional score decreased (Preoperative: 18.0 [4.0]; Postoperative: 4.0 [0], P = 0.004). Six patients had sensory disturbance of the lateral femoral cutaneous nerve, four of which recovered completely during follow-up. No other complications related to surgical approach, osteotomy, acetabular displacement, acetabular fixation, and postoperative stage were found. There was no significant vascular, nerve, or visceral injuries in any of the patients. On multiple regression analysis, the probability of the postoperative modified Harris hip score of a hip joint with a preoperative lateral center edge angle ≥4.5° being classified as excellent was six times that of angles <4.5° (Exp[ß]: 6.249, 95% CI: 1.03-37.85, P = 0.046). Regression analysis of other factors found no significant correlation with postoperative functional scores. CONCLUSION: Overall functional scores post-PAO significantly improved, and pain symptoms were significantly reduced. Patients with a preoperative lateral center edge angle ≥4.5° had better joint function after surgery.
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Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Osteotomía/métodos , Recuperación de la Función , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Radiografía , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The mitochondrial DNA m.3243A > G mutation is well-known to cause a variety of clinical phenotypes, including diabetes, deafness, and osteoporosis. Here, we report isolation and expansion of urine-derived stem cells (USCs) from patients carrying the m.3243A > G mutation, which demonstrate bimodal heteroplasmy. USCs with high levels of m.3243A > G mutation displayed abnormal mitochondrial morphology and function, as well as elevated ATF5-dependent mitochondrial unfolded protein response (UPRmt), together with reduced Wnt/ß-catenin signaling and osteogenic potentials. Knockdown of ATF5 in mutant USCs suppressed UPRmt, improved mitochondrial function, restored expression of GSK3B and WNT7B, and rescued osteogenic potentials. These results suggest that ATF5-dependent UPRmt could be a core disease mechanism underlying mitochondrial dysfunction and osteoporosis related to the m.3243A > G mutation, and therefore could be a novel putative therapeutic target for this genetic disorder.
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Factores de Transcripción Activadores/genética , ADN Mitocondrial/genética , Mitocondrias/genética , Enfermedades Mitocondriales/genética , Mutación , Osteoporosis/genética , Células Madre/metabolismo , Factores de Transcripción Activadores/metabolismo , Adulto , Estudios de Casos y Controles , Separación Celular , Células Cultivadas , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Heteroplasmia , Humanos , Masculino , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/orina , Osteogénesis , Osteoporosis/diagnóstico , Osteoporosis/orina , Fenotipo , Células Madre/ultraestructura , Respuesta de Proteína Desplegada , Orina/citología , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Vía de Señalización Wnt , Adulto JovenRESUMEN
To probe into the impact of Bupivacaine on colorectal cancer (CRC) proliferation, apoptosis, and autophagy through regulating the NF-κB signaling pathway. Our work treated CRC cells with Bupivacaine, detected cell vitality through MTT assay, apoptosis through flow cytometry, cell migration through wound healing assay, NF-κB activity through immunofluorescence, inflammatory factor level, including TNF-α, IL-1ß as well as IL-6 through ESLIA, apoptosis factor mRNA expression, including Bcl-2, Bax and caspase-3q through qRT-PCR, and protein expression linking with NF-κB signaling pathway as well as autophagy-related proteins via western blot. In in vivo experiments, we explored the impact of Bupivacaine on tumor volume, tumor and NF-κB expression. The results showed that 1 mM Bupivacaine was available to signally inhibit CRC cell vitality, promoted apoptosis rate and apoptosis gene expression, like Bax, and caspase-3, inhibited Bcl-2 expression, inhibited cancer cell migration, promoted autophagy-related protein LC3B II/LC3B I ratio and beclin-1 expression, and inhibited p62 expression. Additionally, it could elevate inflammatory factor level and induce IKK and IκB phosphorylation as well as NF-κB proteins. In in vivo experiments, Bupivacaine inhibited tumor volume and tumor, as well as NF-κB expression. In short, bupivacaine is available to inhibit CRC proliferation through regulating NF-κB signaling pathway, promote apoptosis and autophagy, and can be used as a potential drug to treat CRC in the future.
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Apoptosis/efectos de los fármacos , Bupivacaína/farmacología , Neoplasias Colorrectales/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Desnudos , FN-kappa B/genéticaRESUMEN
Carbonic anhydrases (CAs) catalyze the synthesis of HCO3- from H2O and CO2. The dysfunction of CAs leads to aqueous humor secretion and high intraocular pressure to cause glaucoma pathogenesis. Methazolamide (MTZ), a CA inhibitor, can effectively treat glaucoma by reducing aqueous humor secretion. We previously reported that carbonic anhydrase I (CA1), a CA family member, was highly expressed in atherosclerotic tissues of the aorta and stimulated atherosclerosis (AS) by promoting calcification. MTZ showed therapeutic and preventive effects on AS in a mouse model. The above findings suggest a relationship between AS and glaucoma. This study explored the possible association between AS prevalence and glaucoma prevalence and the therapeutic effect of MTZ on AS by analyzing medical records. Among 10,751 patients with a primary diagnosis of glaucoma, 699 (6.5%) were also diagnosed with AS. However, the incidences of AS in patients with keratitis and scleritis, which are also ophthalmic diseases, were 2.5% (206/8383 patients) and 3.5% (46/1308 patients), respectively. In the population without ophthalmic records, the AS prevalence was only 1.9% (99,416/5,168,481 patients) (all p values between each group were below 0.001). Among 152,425 patients with a primary diagnosis of AS, 1245 (0.82%) were also diagnosed with glaucoma. Among 199,782 patients with a primary diagnosis of hypertension (excluding AS), 1149 (0.57%) were diagnosed with glaucoma, and among 5,313,433 patients without AS or hypertension, 9513 (0.18%) were diagnosed with glaucoma (all p values between each group were below 0.001). Additionally, among 14 patients who suffered from both AS and glaucoma and were treated with MTZ to cure their glaucoma, 9 of them showed reduced low-density lipoprotein (LDL) levels, the main index of AS, within 3 months after medication use (2.81 ± 0.61 mmol/L vs. 2.38 ± 0.58 mmol/L, p = 0.039). The above findings demonstrated a strong relation between AS and glaucoma and suggested that AS patients with glaucoma were more likely to suffer from angle-closure glaucoma.
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Aterosclerosis/complicaciones , Glaucoma/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Perovskite solar cells (PSCs) have triggered a research trend in solar energy devices in view of their high power conversion efficiency and ease of fabrication. However, more delicate strategies are still required to suppress carrier recombination at charge transfer interfaces, which is the necessary path to high-efficiency solar cells. Here, a p-p+ homojunction was constructed on basis of NiO film to enhance hole transfer in an inverted planar perovskite solar cell. The homojunction was generated by fabricating a NiO/Cu:NiO bilayer film. The density functional theory calculation demonstrated the charge density difference in the two layers, which could generate a space charge region and a band bending at the junction, and the result was further proved by energy level structure analysis of NiO and Cu:NiO films. The designed homojunction could accelerate the hole transfer and inhibit carrier recombination at the interface between hole transfer layer and perovskite layer. Finally, the inverted planar perovskite solar cell with p-p+ homojunction showed an efficiency of 18.30 % and a high fill factor of 0.81, which were much higher than the counterpart of the PSCs individually using NiO or Cu:NiO as hole transfer layer. This work developed a new structure of hole transport layer to enhance the performance of PSCs, and also provided new ideas for design of charge transfer films.
RESUMEN
Aim: This study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA). Methods: Synovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Results: Immunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P<0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P<0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P<0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P<0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P<0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently. Conclusion: VDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.