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Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.
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Apoptose , Dexametasona , Canais Iônicos , Osteócitos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Estresse Mecânico , Osteócitos/metabolismo , Osteócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Camundongos , Canais Iônicos/metabolismo , Canais Iônicos/genética , Transdução de Sinais/efeitos dos fármacos , Dexametasona/farmacologia , Linhagem CelularRESUMO
PURPOSE: To determine the model performance of artificial intelligence (AI) in detecting rotator cuff pathology using different imaging modalities and to compare capability with physicians in clinical scenarios. METHODS: The review followed the PRISMA guidelines and was registered on PROSPERO. The criteria were as follows: 1) studies on the application of AI in detecting rotator cuff pathology using medical images, and 2) studies on smart devices for assisting in diagnosis were excluded. The following data were extracted and recorded: statistical characteristics, input features, AI algorithms used, sample sizes of training and testing sets, and model performance. The data extracted from the included studies were narratively reviewed. RESULTS: A total of 14 articles, comprising 23,119 patients, met the inclusion and exclusion criteria. The pooled mean age of the patients was 56.7 years, and the female rate was 56.1%. The area under the curve (AUC) of the algorithmic model to detect rotator cuff pathology from ultrasound images, MRI images, and radiographic series ranged from 0.789 to 0.950, 0.844 to 0.943, and 0.820 to 0.830, respectively. Notably, 1 of the studies reported that AI models based on ultrasound images demonstrated a diagnostic performance similar to that of radiologists. Another comparative study demonstrated that AI models using MRI images exhibited greater accuracy and specificity compared to orthopedic surgeons in the diagnosis of rotator cuff pathology, albeit not in sensitivity. CONCLUSIONS: The detection of rotator cuff pathology has been significantly aided by the exceptional performance of AI models. In particular, these models are equally adept as musculoskeletal radiologists in using ultrasound to diagnose rotator cuff pathology. Furthermore, AI models exhibit statistically superior levels of accuracy and specificity when using MRI to diagnose rotator cuff pathology, albeit with no marked difference in sensitivity, in comparison to orthopaedic surgeons. LEVEL OF EVIDENCE: Level III, systematic review of Level III studies.
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Lesões do Manguito Rotador , Manguito Rotador , Humanos , Feminino , Pessoa de Meia-Idade , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/patologia , Inteligência Artificial , Imageamento por Ressonância Magnética , AlgoritmosRESUMO
PURPOSE: To develop the machine learning model to predict clinical outcomes following MPFLR and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: 1) concurrent bony procedures, 2) history of other knee surgeries, and 3) follow-up period of less than 12 months. Forty-two predictive models were constructed for seven clinical outcomes (failure to achieve MCID of clinical scores, return to pre-injury sports, pivoting sports, and recurrent instability) using six machine learning algorithms (Random Forest, Logistic Regression, Support Vector Machine, Decision Tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. Additionally, Shapley Additive Explanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the MCID for Lysholm, IKDC, Kujala, and Tegner scores, the AUCs and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to pre-injury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to pre-injury sports, while absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSION: The predictive models developed using machine learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.
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PURPOSE: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT. METHODS: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs. RESULTS: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]. CONCLUSION: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT. LEVEL OF EVIDENCE: IV.
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Doenças Ósseas , Doenças das Cartilagens , Osteoartrite , Humanos , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Índice de Massa Corporal , Medula Óssea , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Osteoartrite/patologia , Doenças das Cartilagens/patologia , Doenças Ósseas/patologiaRESUMO
BACKGROUND: We sought to determine the diagnostic efficacy of Breast-specific gamma imaging (BSGI) in Chinese women with BI-RADS 4 category lesions and to compare this efficacy to that of ultrasound/mammography. METHODS: We retrospectively analyzed data from 177 women that had undergone BSGI of BI-RADS 4 category lesions originally detected via ultrasound and/or mammography. RESULTS: Of these 177 cases, 117 (66.1%) were malignant lesions and 60 (33.9%) were benign. The sensitivity, specificity, positive predictive values, and negative predictive values of BSGI were 94.9% (111/117), 78.3% (47/60), 89.5% (111/124), and 88.7% (47/53), respectively. The specificity and positive predictive values for mammography were 48.3% (29/60) and 77.5% (107/138), while for ultrasound they were 53.3% (32/60) and 79.6% (109/137), respectively. The sensitivity and specificity of BSGI for the detection of lesions ≤1 cm in size were 90.9% (10/11) and 88.0% (22/25), respectively, while for breast lesions >1 cm in size these values were 94.3% (100/106) and 71.4% (25/35), respectively. In addition, BSGI sensitivity and specificity values for dense breast tissue were 94.0% (79/84) and 78.0% (39/50), respectively, whereas for non-dense breast tissue these vales were 97.0% (32/33) and 80.0% (8/10), respectively. The sensitivity of BSGI for invasive ductal carcinomas (IDC) and ductal carcinomas in situ (DCIS) was 98.9% (95/96) and 75.0% (9/12), respectively. The tumor to normal tissue ratio of BSGI for malignant lesions was significantly higher than for benign lesions (2.18 ± 1.17 vs 1.66 ± 0.40, t = 7.56, P<0.05). CONCLUSIONS: These results indicate that BSGI is highly sensitive for the detection of such lesions, achieving good positive/negative predictive values. This suggests that for IDC in particular, BSGI is superior to ultrasound and mammography for the diagnosis of BI-RADS 4 category lesions, although this was less apparent for the diagnosis of DCIS lesions. BSGI exhibited excellent performance in dense breast tissue and for the detection of lesions ≤1 cm in size.
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Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Imageamento por Ressonância Magnética/métodos , Cintilografia/métodos , Tecnécio Tc 99m Sestamibi/metabolismo , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/metabolismo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Mammography (MMG) shows decreased diagnostic accuracy in dense breast tissue, and thus, ultrasonography (US) and breast-specific gamma imaging (BSGI) have gradually been adopted for women with mammographically dense breasts. However, these two adjunct modalities have not been directly compared in previous studies. Hence, we investigated the adjunctive efficacy of US and BSGI in mammographically dense breasts. METHODS: This retrospective, comparative study recruited women with mammographically dense breasts. All enrolled women underwent US and BSGI as adjunctive imaging, and the comparative sensitivity, specificity, and diagnostic accuracy of combined MMG plus BSGI versus MMG plus US were evaluated. McNemar's test was used for paired binary data in this comparative analysis. RESULTS: From April 2013 to April 2016, 364 women with mammographically dense breasts and a final surgical or biopsy pathological diagnosis were recruited, comprising 218 cases of malignant disease (59.9%) and 146 cases of benign disease (40.1%). There was no difference between BSGI and US in enhancing the sensitivity of MMG diagnosis (Se-Difference 3.2%, p = 0.23), but the diagnostic specificity of MMG plus BSGI was superior to that of MMG plus US (Sp-Difference 10.3%, p = 0.003). The area under the ROC curve showed that MMG plus BSGI had better diagnostic accuracy than MMG plus US (0.90 vs. 0.83, p = 0.0019). CONCLUSIONS: For women with mammographically dense breasts, MMG plus BSGI or US can improve the diagnostic accuracy. In addition, BSGI has high specificity and could reduce invasive biopsies and thus may represent a viable diagnostic imaging alternative for mammographically dense breasts. KEY POINTS: ⢠Both BSGI and US can be applied as adjunct imaging diagnostics in women with mammographically dense breasts. ⢠The diagnostic accuracy of MMG plus BSGI was higher than that of MMG plus US. ⢠BSGI has the potential to be used as an adjunct diagnostic modality in women with mammographically dense breasts.
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Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Cintilografia/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Biópsia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Breast cancer is a leading cause of cancer in females, and is the second leading cancer-related cause of death in this group. Early diagnosis is essential to breast cancer to be effectively treated, and ultrasound, mammography, and magnetic resonance imaging (MRI) represent three key technologies that are utilized for the diagnosis of breast lesions. Breast-specific gamma imaging (BSGI) is an approach to molecular breast imaging that allows for high-resolution radio-imaging that is not adversely impacted by breast tissue density. This study was therefore designed to assess the relative diagnostic efficacy of BSGI, MRI, mammography, and ultrasound in different molecular subtypes of breast cancer among Chinese women. METHODS: Diagnostic findings from 390 patients that had undergone diagnosis and treatment in our breast surgery department were retrospectively reviewed. Patients had been diagnosed via BSGI, mammography, ultrasound, and MRI. The diagnostic efficacy of these different imaging modalities and their associated biological characteristics were compared in the present study. RESULTS: A total of 229 of these 390 patients (58.7%) were diagnosed with malignant breast cancer, with the remaining 161 (41.3%) cases having been found to be benign. BSGI, MRI, mammography, and ultrasound yielded respective sensitivity values of 91.7, 92.5, 77.3, and 82.1%, while the respective specificity values for these imaging modalities were 80.7, 69.7, 74.5, and 70.8%. For lesions > 1 cm, BSGI offered a sensitivity of 92.5%. For mammographic breast density A, B, C, and D, BSGI offered a sensitivity of 93.3, 94.0, 91.5, and 89.3%, respectively. BSGI also yielded a significantly higher lesion-to-normal lesion ratio (LNR) for malignant lesions relative to benign lesions (2.76 ± 1.32 vs 1.46 ± 0.49). CONCLUSIONS: These findings confirm that BSGI is highly sensitive and is superior to mammography in the detection and diagnosis of ductal carcinomas in situ (DCIS). Such diagnostic efficacy can be further improved by using BSGI as an auxiliary modality to mammography and ultrasound, potentially improving the reliability of breast lesion diagnosis, thereby ensuring that patients receive rapid and effective treatment without the risk of misdiagnosis or unnecessary surgical treatment.
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Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Imagem Molecular/métodos , Ultrassonografia Mamária/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade da Mama , Criança , Pré-Escolar , China , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
RATIONALE: The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell-based myocardial therapy are needed. OBJECTIVE: The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation. METHODS AND RESULTS: MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications. CONCLUSIONS: Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted.
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Precondicionamento Isquêmico Miocárdico/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Infarto do Miocárdio/terapia , Revascularização Miocárdica , Comunicação Parácrina/fisiologia , Animais , Hipóxia Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Macaca fascicularis , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Primatas , Transplante Homólogo/métodosRESUMO
BACKGROUND: Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. METHODS: During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. RESULTS: A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). CONCLUSIONS: BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer.
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Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Adulto , Idoso , Mama/patologia , Mama/fisiologia , Mama/cirurgia , Densidade da Mama , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , China , Feminino , Raios gama , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Sensibilidade e Especificidade , Tecnécio Tc 99m Sestamibi/administração & dosagem , UltrassonografiaRESUMO
The purpose of this meta-analysis was to conduct a comparative analysis of clinical scores and complication rates among patients experiencing recurrent patellar dislocation who underwent medial patellofemoral ligament (MPFL) reconstruction using both single and double tunnel techniques. A comprehensive search was conducted across electronic databases including PubMed, the Cochrane Library, Web of Science, and Google Scholar to retrieve articles relevant to MPFL reconstruction utilising the tunnel technique. Subsequently, meta-analyses were undertaken to assess complication rates and changes in clinical scores before and after surgery. Following this, sensitivity analysis and meta-regression analysis were performed to scrutinise potential confounding variables. A total of thirty-two studies were included in the analysis, comprising twenty-seven non-comparative studies and five comparative studies. The findings revealed a similarity in postoperative complication rates between the single and double tunnel fixation techniques: [9.0% (95%CI, 4.0%-15.6%) versus 8.9% (95%CI, 4.7%-14.1%, p = 0.844)]. Likewise, no statistically significant differences were observed in Lysholm scores [34.1 (95%CI, 26.7-41.5) versus 33.8 (95%CI, 27.7-40.0, p = 0.956)], Kujala scores [29.4 (95%CI, 22.3-36.4) versus 27.3 (95%CI, 22.3-32.3, p = 0.637)], and Tegner score change [1.1 (95%CI, 0.8-1.4) versus 0.7 (95%CI, -0.2-1.6, p = 0.429)] before and after MPFL reconstruction, respectively, using these two techniques. In conclusion, the authors found that the clinical functional improvement and complication rates in MPFL reconstruction using the single tunnel fixation technique are comparable to those achieved with the double tunnel fixation approach. However, to further advance the understanding in this field, additional randomised controlled studies must be conducted to provide further insights. Key Words: MPFL reconstruction, Bone tunnel, Patellar dislocation, Meta-analysis.
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Luxação Patelar , Articulação Patelofemoral , Procedimentos de Cirurgia Plástica , Humanos , Luxação Patelar/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Articulação Patelofemoral/cirurgia , Resultado do Tratamento , Ligamentos Articulares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Ligamento Patelar/cirurgiaRESUMO
Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.
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N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.
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Metiltransferases , Osteoblastos , Animais , Camundongos , Proliferação de Células , Metiltransferases/metabolismo , Osteoblastos/metabolismo , RNA , RNA Mensageiro/metabolismoRESUMO
This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.
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Compostos de Organotecnécio/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Feminino , Camundongos , Imagem de Perfusão do Miocárdio , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Distribuição TecidualRESUMO
Background: Bone bruises and concomitant ligament injuries after anterior cruciate ligament (ACL) injuries have attracted attention, but their correlation and potential clinical significance remain unclear. Purpose: To assess the relationship between bone bruises and concomitant ligamentous injuries in ACL injuries. Study design: Systematic review. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to October 20, 2021. All articles that evaluated the relationship between bone bruises and related ligaments injuries were included. Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment as well as Review Manager 5.3 was used for data analysis. Results: A total of 19 studies evaluating 3292 patients were included. After meta-analysis, anterolateral ligament (ALL) injuries were associated with bone bruising on the lateral tibial plateau (LTP) (RR = 2.33; 95% CI 1.44-3.77; p = 0.0006), lateral femoral condyle (LFC) (RR = 1.97; 95% CI 1.37-2.85; p = 0.0003) and medial tibial plateau (MTP) (RR = 1.62; 95% CI 1.24-2.11; p = 0.0004); Moreover, medial collateral ligament (MCL) injuries were associated with bone bruising on the femur (RR = 1.49; 95% CI 1.17-1.90; p = 0.001), and no statistical significance was found between bone bruising on the MTP and Kaplan fiber (KF) injuries (RR = 1.58; 95% CI 1.00-2.49; p = 0.05). Nonetheless, the current evidence did not conclude that bone bruises were associated with lateral collateral ligament (LCL) injuries. Conclusion: For individuals with an ACL injury, bone bruises of the LTP, LFC, and MTP can assist in the diagnosis of ALL injuries. Furthermore, femoral bruising has potential diagnostic value for MCL injuries. Knowing these associations allows surgeons to be alert to ACL-related ligament injuries on MRI and during operations in future clinical practice.
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Background: Patellar dislocation is attracting considerable research interest. Purpose: To assess studies on patellar dislocation using a scientometric method to better understand the current status of research and explore future study directions. Study Design: Scoping review. Methods: The Web of Science Core Collection database was selected to retrieve publications on patellar dislocation. Articles and reviews written in English with patellar dislocation as the main topic were included. Conference abstracts, notes, letters, expert opinions, and animal studies were excluded. A total of 4632 articles were identified in our initial search. In addition, Excel 2019, CiteSpace 6.1.R1, and VOSviewer 1.6.9 were used to analyze the h-index, the most highly cited publication, publication essentials, and research themes. Results: A total of 1485 articles were included in our analysis, with 36,608 citations and an h-index of 93. Overall, 1494 institutions and 195 journals were identified from these studies. The United States (n = 531) was the most productive country. The institution and journal with the largest number of articles were the Hospital for Special Surgery (n = 59) and Knee Surgery, Sports Traumatology, Arthroscopy (n = 212), respectively. The article "Scoring of Patellofemoral Disorders" by Kujala et al in 1993 was the most highly cited reference. The most commonly found terms used were patellar dislocation, patellar instability, medial patellofemoral ligament, knee, recurrent patellar dislocation, and soft tissue restraints. Four topics were identified after clustering analysis of key terms: risk factors, medial patellofemoral ligament reconstruction, patellar dislocation in skeletally immature patients, and lateral retinacular release. Conclusion: This scientometric review of articles on patellar dislocation summarized the current status of research (countries, institutions, and authors) and identified potential research directions.
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BACKGROUND: The present retrospective study was designed to evaluate the relative diagnostic utility of breast-specific gamma imaging (BSGI) and breast magnetic resonance imaging (MRI) as means of evaluating female breast cancer patients in China. METHODS: A total of 229 malignant breast cancer patients underwent ultrasound, mammography, BSGI, and MRI between January 2015 and December 2018 for initial tumor staging. Of these patients, 73 were subsequently treated via definitive breast surgery following neoadjuvant chemotherapy (NAC), of whom 17 exhibited a complete pathologic response (pCR) to NAC. RESULTS: BSGI and MRI were associated with 76.8% (43/56) and 83.9% (47/56) sensitivity (BSGI vs. MRI, p = 0.341) values, respectively, as a means of detecting residual tumors following NAC, while both these approaches exhibited comparable specificity in this diagnostic context. The specificity of BSGI for detecting residual tumors following NAC was 70.6% (12/17), and that of MRI was 58.8% (10/17) (BSGI vs. MRI, p = 0.473). CONCLUSION: These results demonstrate that BSGI is a useful auxiliary approach to evaluating pCR to NAC treatment.
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The aim of this study was to evaluate the clinical value of 18-fluorodeoxyglucose (FDG) imaging with gamma-camera positron emission tomography (GCPET) equipped with a one-inch crystal for diagnosing lung lesions and determining the stage of non-small cell lung cancer (NSCLC) in regions with a high prevalence of inflammatory disease and tuberculosis. FDG-GCPET was used to examine 103 patients with suspected malignant lesions in the lung. The results of FDG-GCPET and conventional workup (CWU) including computed tomography (CT), ultrasonography and radionuclide bone scintigraphy were compared. The final diagnosis was based on the results of a histological analysis or follow-up of at least six months. The results showed 82 patients with malignant and 21 patients with benign lesions. If a lesion to background ratio > or = 2.0 was used as the threshold, then the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of FDG-GCPET for NSCLC were 93.9, 57.1, 86.4, 89.5 and 70.6%, respectively. In 36 patients who underwent open-chest surgery, the diagnostic positive values of FDG-GCPET and CT for lymph-node involvement were 85% (17/20) and 65% (13/20), respectively. The diagnostic sensitivity, specificity, accuracy, PPV and NPV of FDG imaging were 85, 81.3, 83.3, 85 and 81.3%, respectively compared to the CT values of 65, 75, 69.4, 76.5 and 63.2%, respectively (NS). For the evaluation of distant metastases, 31 true-positive patients were identified during the follow-up. FDG imaging correctly identified 28 patients compared to 25 by CWU. In conclusion, FDG imaging with GCPET equipped with a one-inch crystal revealed a high lesion detection capability but a low level of clinical effectiveness for differentiating between malignant and benign lesions in the lung in regions with a high prevalence of inflammatory disease and tuberculosis. For N and M staging of NSCLC, this method may provide additional data that are not available from the CWU.
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Fluordesoxiglucose F18 , Câmaras gama , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: The aim of this study was to evaluate the potential role of F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in assessing the chemotherapy response of osteosarcoma when compared with histologically assessed tumor necrosis. METHODS: Fifteen patients were examined with whole-body FDG-PET prior to and following neoadjuvant therapy. The maximum standard uptake value (SUV max) of tumor and tumor to background ratio (TBR) prior to and following chemotherapy was used for semiquantitative PET imaging analysis. The SUV max of prechemotherapy and post-chemotherapy was recorded as SUV1 and SUV2. TBR1 and TBR2 represented prechemotherapy and post-chemotherapy TBR. TBR was calculated by drawing an identical region of interest over the tumor and the contralateral normal limb or pelvis. Tumor necrosis was classified according to Salzer-Kuntschik's criteria. RESULTS: Eight patients with more than 90% tumor necrosis were classified as showing good responses and seven patients with less than 90% tumor necrosis as showing poor responses. SUV2/SUV1, TBR2/TBR1, and TBR2 were significantly correlated with the tumor necrosis degree (P < 0.01, P < 0.001, P < 0.001). TBR2/TBR1 were below 0.46 in all the patients with favorable responses, and higher than 0.49 in all the patients with unfavorable responses. However, it was difficult to distinguish good responses from poor responses by SUV2/SUV1. CONCLUSIONS: FDG-PET is a promising tool to assess the chemotherapy response of osteosarcoma noninvasively. The TBR was better than SUV max in evaluating the chemotherapy response in this study.
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Antineoplásicos/administração & dosagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia , Fluordesoxiglucose F18 , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/terapia , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Quimioterapia Adjuvante/métodos , Criança , Feminino , Humanos , Masculino , Necrose/diagnóstico por imagem , Necrose/prevenção & controle , Necrose/terapia , Prognóstico , Compostos Radiofarmacêuticos , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to investigate the clinical factors related to hematologic toxicity caused by treatment with samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP). MATERIALS AND METHODS: A total of 206 secondary bone neoplasm patients treated with 153Sm-EDTMP were analyzed retrospectively. Logistic regression (SPSS 10.0 for Windows; Chicago, IL) and correlation analysis were used to evaluate the factors concerned. RESULTS: Age, number of bone metastatic lesions, chemotherapy before treatment with 153Sm-EDTMP, concurrence of radiotherapy, and times of repeated treatments with 153Sm-EDTMP were determined by single factor analysis to be related to hematologic toxicity. Chemotherapy before treatment with 153Sm-EDTMP, concurrence of radiotherapy, drug use to maintain normal white blood cell counts, and times of repeated treatments with 153Sm-EDTMP were determined by multiple factor analysis to be related to hematologic toxicity. CONCLUSIONS: Chemotherapy before treatment with 153Sm-EDTMP, concurrence of radiotherapy, drug use to maintain normal white blood cell counts, and times of repeated treatments with 153Sm-EDTMP are the main clinical factors related to hematologic toxicity caused by 153Sm-EDTMP therapy. In patients with such factors, more attention might be paid to the change of blood cell counts after 153Sm-EDTMP therapy.