RESUMO
INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Masculino , Feminino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Pessoa de Meia-Idade , Idoso , Prognóstico , Estudos Retrospectivos , Dosagem Radioterapêutica , Adulto , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Intervalo Livre de Doença , Radioterapia AdjuvanteRESUMO
BACKGROUND: In esthetic dentistry, a thorough esthetic analysis holds significant role in both diagnosing diseases and designing treatment plans. This study established a 3D esthetic analysis workflow based on 3D facial and dental models, and aimed to provide an imperative foundation for the artificial intelligent 3D analysis in future esthetic dentistry. METHODS: The established 3D esthetic analysis workflow includes the following steps: 1) key point detection, 2) coordinate system redetermination and 3) esthetic parameter calculation. The accuracy and reproducibility of this established workflow were evaluated by a self-controlled experiment (n = 15) in which 2D esthetic analysis and direct measurement were taken as control. Measurement differences between 3D and 2D analysis were evaluated with paired t-tests. RESULTS: 3D esthetic analysis demonstrated high consistency and reliability (0.973 < ICC < 1.000). Compared with 2D measurements, the results from 3D esthetic measurements were closer to direct measurements regarding tooth-related esthetic parameters (P<0.05). CONCLUSIONS: The 3D esthetic analysis workflow established for 3D virtual patients demonstrated a high level of consistency and reliability, better than 2D measurements in the precision of tooth-related parameter analysis. These findings indicate a highly promising outlook for achieving an objective, precise, and efficient esthetic analysis in the future, which is expected to result in a more streamlined and user-friendly digital design process. This study was registered with the Ethics Committee of Peking University School of Stomatology in September 2021 with the registration number PKUSSIRB-202168136.
Assuntos
Estética Dentária , Dente , Humanos , Reprodutibilidade dos Testes , Fluxo de Trabalho , Face , Desenho Assistido por ComputadorRESUMO
PURPOSE: To explore the clinical application of one-piece polyetheretherketone (PEEK) removable partial dentures (RPDs) fabricated using a novel digital workflow and to evaluate their weights and fits in vivo and patient satisfaction. MATERIALS AND METHODS: Fifteen cases with posterior partially edentulous situations were selected, and each patient received two types of RPDs, including a novel digital workflow (test group) and a conventional workflow (control group). For the test group, one-piece RPDs were designed through three-dimensional (3D) methods by scanning stone casts and fabricated by milling PEEK discs. Each RPD was weighed. The gaps between the oral tissue and RPDs in each group were duplicated using a polyvinylsiloxane (PVS) replica and measured by 3D analysis. A visual analog scale (VAS) was used to evaluate the patient's satisfaction. Paired t-tests were used to compare the differences in the weight, the gaps of each RPD, and VAS values between the two groups. One-way analysis of variance tests was used to compare the differences in the gap among different components in each group. RESULTS: The RPD in the test group weighed less than that in the control group (p < 0.01). No statistically significant differences in the gaps of denture bases and rests (p > 0.05) were found between the two groups, but the gaps of major connectors in the test group were significantly smaller than in the control group (p < 0.05). The VAS scores for comfortableness and masticatory efficiency were not significantly different between the two groups (p > 0.05) but the scores for the aesthetic appearance of the clasps in the test group were significantly higher than that in the control group (p < 0.05). CONCLUSIONS: One-piece PEEK RPDs manufactured using a novel digital workflow weighed less than conventional RPDs and exhibited a clinically acceptable internal fit. Although the aesthetic appearance of the PEEK clasps was superior to the control, there is still room for improvement.
RESUMO
OBJECTIVES: Accuracy is a crucial factor when assessing the quality of digital impressions. This systematic review aims to assess the accuracy of intraoral scan (IOS) in obtaining digital impressions of edentulous jaws. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022382983). A thorough retrieval of 7 electronic databases was undertaken, encompassing MEDLINE (PubMed), Web of Science, EMBASE, Scopus, Cochrane Library, Virtual Health Library, and Open gray, through September 11, 2023. A snowball search was performed by tracing the reference lists of the included studies. The Population, Intervention, Comparison, and Outcome (PICO) question of this systematic review was: "What is the accuracy of intraoral scan in obtaining digital impressions of edentulous arches?" The Modified Methodological Index for Nonrandomized Studies (MINORS) was employed to assess the risk of bias. RESULTS: Among the studies retrieved from databases and manual search, a total of 25 studies were selected for inclusion in this systematic review, including 9 in vivo and 16 in vitro studies. Twenty-one of the included studies utilized the 3D deviation analysis method, while 4 studies employed the linear or angular deviation analysis method. The accuracy results of in vitro studies indicated a trueness range of 20-600⯵m and a precision range of 2-700⯵m. Results of in vivo studies indicated a trueness range of 40-1380⯵m, while the precision results were not reported. CONCLUSION: According to the results of this study, direct digital impressions by IOS cannot replace the conventional impressions of completely edentulous arches in vivo. Edentulous digital impressions by IOS demonstrated poor accuracy in peripheral areas with mobile tissues, such as the soft palate, vestibular sulcus, and sublingual area.
RESUMO
Bio-inspired hydrogel robots have become promising due to their advantage of the interaction safety and comfort between robots and humans, while current hydrogel robots mainly focus on underwater movement due to the hydration-dehydration process of thermo-responsive hydrogels, which greatly limits their practical applications. To expand the motion of the thermo-responsive hydrogel robot to the ground, we constructed a hydrogel robot inspired by a caterpillar, which has an anisotropic double-layered structure by the interfacial diffusion polymerization method. Adding PVA and SA to PNIPAm will cause different conformation transitions. Therefore, sticking the two layers of hydrogel together will form a double-layer anisotropic structure. The ultra-high hydrophilicity of PVA and SA significantly reduces the contact angle of the hydrogel from 53.1° to about 10° and reduces its hydration time. The responsive time for bending 30° of the hydrogel robot has been greatly reduced from 1 h to half an hour through the enhancement of photo-thermal conversion and thermal conductivity via the addition of Fe3O4 nanoparticles. As a result, the fabricated hydrogel robot can achieve a high moving speed of 54.5 mm·h-1 on the ground. Additionally, the fabricated hydrogel has excellent mechanical strength and can endure significant flexibility tests. This work may pave the road for the development of soft robots and expand their applications in industry.
RESUMO
BACKGROUND: In the realm of cancer studies,the differences among the biological behavior of oligometastatic prostate cancer (OPCa), localized prostate cancer (LPCa), and widely prostate cancer (WPCa) are still unclear. OBJECTIVES: The purpose of our study was to assess the clinical and intravoxel incoherent motion (IVIM) parameters of tumor burden in OPCa. In addition, the correlation between clinical and IVIM parameters and the prostate-specific antigen nadir (PSAN) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) in OPCa was explored. It was found that the IVIM parameters could effectively differentiate LPCa and WPCa, as well as LPCa and OPC. Moreover, Gleason score (GS) was positively correlated with PSAN, while prostate volume was positively correlated with TTN. METHODS: About 54 patients were included in this retrospective study (mean age=74±7.4 years). ADC, D, D*, and f were acquired according to the biexponential Diffusion Weighted Imaging (DWI) model. The Kruskal-Wallis test was used to test the differences in clinical and IVIM parameters among the three groups. The Receiver Operating Characteristic (ROC) curve was used to evaluate the discrimination abilities. The Area Under the Curve (AUC) was compared using the DeLong test. Furthermore, Spearman correlation analysis was performed to assess the correlation between clinical and IVIM parameters of PSAN and TTN during initial ADT with OPCa. RESULTS: There were significant differences among the three groups observed for age, PSA, GS, ADC, D and D* values (P<0.05). Multi-parameter pairwise comparison results showed that significant differences between LPCa and WPCa were observed for the age, PSA, GS, ADC, D and D* values (P<0.05). However, D* was different between the LPCa and OPCa groups (P=0.032). GS showed a significant positive correlation with PSAN (Rho=0.594, P=0.042), and prostate volume showed a significant positive correlation with TTN (Rho=0.777, P=0.003). CONCLUSIONS: The IVIM parameters can effectively differentiate LPCa and WPCa, as well as LPCa and OPCa. Moreover, there was a certain trend in their distribution, which could reflect the tumor burden of PCa.
RESUMO
Purpose: Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC. Methods and Materials: A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests. Results: A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; P < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; P < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; P < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; P < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; P = .002). Conclusions: In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.
RESUMO
INTRODUCTION: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge. METHODS: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (nâ¯=â¯197) and validation (nâ¯=â¯84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators. RESULTS: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC)â¯=â¯0.726, 3-year AUCâ¯=â¯0.727, and 5-year AUCâ¯=â¯0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUCâ¯=â¯0.682, 3-year AUCâ¯=â¯0.734, and 5-year AUCâ¯=â¯0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model. CONCLUSION: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.
Assuntos
Carcinoma de Células Renais , Genômica , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Prognóstico , Feminino , Masculino , Genômica/métodos , Pessoa de Meia-Idade , Nomogramas , IdosoRESUMO
Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.
Assuntos
Exossomos , Vesículas Extracelulares , MicroRNAs , MicroRNAs/genética , Vesículas Extracelulares/metabolismo , Exossomos/genética , Exossomos/metabolismo , Regeneração Óssea , OsteogêneseRESUMO
Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.
Assuntos
Materiais Biocompatíveis , Implantes Dentários , Peri-Implantite , Peri-Implantite/terapia , Peri-Implantite/prevenção & controle , Peri-Implantite/tratamento farmacológico , Humanos , Implantes Dentários/normas , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Propriedades de Superfície , Antibacterianos/uso terapêutico , Antibacterianos/farmacologiaRESUMO
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into cells of different lineages to form mesenchymal tissues, which are promising in regard to treatment for bone diseases. Their osteogenic differentiation is under the tight regulation of intrinsic and extrinsic factors. Transforming growth factor ß (TGF-ß) is an essential growth factor in bone metabolism, which regulates the differentiation of MSCs. However, published studies differ in their views on whether TGF-ß signaling regulates the osteogenic differentiation of MSCs positively or negatively. The controversial results have not been summarized systematically and the related explanations are required. Therefore, we reviewed the basics of TGF-ß signaling and summarized how each of three isoforms regulates osteogenic differentiation. Three isoforms of TGF-ß (TGF-ß1/ß2/ß3) play distinct roles in regulating osteogenic differentiation of MSCs. Additionally, other possible sources of conflicts are summarized here. Further understanding of TGF-ß signaling regulation in MSCs may lead to new applications to promote bone regeneration and improve therapies for bone diseases.
Assuntos
Osso e Ossos , Diferenciação Celular , Células-Tronco Mesenquimais , Osteogênese , Transdução de Sinais , Fator de Crescimento Transformador beta , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Fator de Crescimento Transformador beta/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/citologia , AnimaisRESUMO
To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > - 2.0) and low BMD group (QCT Z-score ≤ - 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P < 0.001). The VBQ score was significantly negative correlated with QCT Z score (r = - 0.454, P < 0.001). On multivariate analysis, VBQ score was independently associated with low BMD (OR: 4.134, 95% CI 2.136-8.000, P < 0.001). The area under the ROC curve indicated that the diagnostic accuracy of the VBQ score for predicting low BMD was 81%. A sensitivity of 65.9% with a specificity of 88.4% could be achieved for distinguishing low BMD by setting the VBQ score cutoff as 3.18. The novel VBQ score was a promising tool in distinguishing low BMD in patients with AIS and could be useful as opportunistic assessment for screening and complementary evaluation to QCT before surgery.
Assuntos
Densidade Óssea , Imageamento por Ressonância Magnética , Escoliose , Humanos , Escoliose/diagnóstico por imagem , Adolescente , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Curva ROC , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Criança , Tomografia Computadorizada por Raios X/métodos , Estudos RetrospectivosRESUMO
Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.
RESUMO
BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Radioterapia Adjuvante/métodos , RadiômicaRESUMO
Purpose: We aimed to integrate MR radiomics and dynamic hematological factors to build a model to predict pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in esophageal squamous cell carcinoma (ESCC). Methods: Patients with ESCC receiving NCRT and esophagectomy between September 2014 and September 2022 were retrospectively included. All patients underwent pre-treatment T2-weighted imaging as well as pre-treatment and post-treatment blood tests. Patients were randomly divided to training set and testing set at a ratio of 7:3. Machine learning models were constructed based on MR radiomics and hematological factors to predict pCR, respectively. A nomogram model was developed to integrate MR radiomics and hematological factors. Model performances were evaluated by areas under curves (AUCs), sensitivity, specificity, positive predictive value and negative. Results: A total of 82 patients were included, of whom 39 (47.6 %) achieved pCR. The hematological model built with four hematological factors had an AUC of 0.628 (95%CI 0.391-0.852) in the testing set. Two out of 1106 extracted features were selected to build the radiomics model with an AUC of 0.821 (95%CI 0.641-0.981). The nomogram model integrating hematological factors and MR radiomics had best predictive performance, with an AUC of 0.904 (95%CI 0.770-1.000) in the testing set. Conclusion: An integrated model using dynamic hematological factors and MR radiomics is constructed to accurately predicted pCR to NCRT in ESCC, which may be potentially useful to assist individualized preservation treatment of the esophagus.
RESUMO
Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.
Assuntos
Regeneração Óssea , Proteínas de Ligação ao Cálcio , Colágeno , Durapatita , Proteína de Matriz Gla , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Regeneração Óssea/genética , Regeneração Óssea/imunologia , Animais , Durapatita/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Camundongos , Colágeno/metabolismo , Colágeno/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteogênese/imunologia , Diferenciação Celular/genética , Materiais BiocompatíveisRESUMO
While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting ß-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis. Additionally, conditional Ube2c knockout mice exhibited enhanced osteoclastic activity and reduced osteogenic differentiation. Furthermore, human BMSCs with stable UBE2C knockdown exhibited diminished capacity for osteogenic differentiation. Mechanistically, we discovered that UBE2C binds to and stabilizes SMAD1/5 protein expression levels. Interestingly, UBE2C's role in regulating osteogenic differentiation and SMAD1/5 expression levels appears to be independent of its enzymatic activity. Notably, UBE2C regulates osteogenic differentiation through SMAD1/5 signaling. In conclusion, our findings underscore the pivotal role of UBE2C in bone formation, emphasizing its contribution to enhanced osteogenic differentiation through the stabilization of SMAD1/5. These results propose UBE2C as a promising target for BMSC-based bone regeneration.
Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais , Camundongos Knockout , Osteogênese , Proteína Smad1 , Proteína Smad5 , Enzimas de Conjugação de Ubiquitina , Animais , Osteogênese/fisiologia , Proteína Smad1/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Humanos , Diferenciação Celular/fisiologia , Proteína Smad5/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Transdução de Sinais , Proliferação de Células , Estabilidade Proteica , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoclastos/citologiaRESUMO
BACKGROUND: More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS: In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS: A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION: A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Radiômica , AlgoritmosRESUMO
Sn doping is usually adopted to prepare Ti3AlC2 in mass production because it can reduce the synthesis temperature while increasing the phase purity. However, excessive Sn doping usually deteriorates the oxidation resistance of Ti3AlC2. Therefore, an appropriate Sn doping concentration is a vital issue. In this work, the effect of Sn doping concentration on the oxidation behavior of Ti3AlC2 was systematically investigated by combining theoretical calculations and experimental methods. Density function theory calculations suggest that the oxygen adsorption mechanisms for the (001) surface of Ti3AlC2 with and without Sn doping are similar, and Ti-O bonds are always preferentially formed. The molecular dynamics simulation further indicates that Al atoms have a faster diffusion rate during the oxidation process. Therefore, a continuous Al2O3 layer can form rapidly at high temperature. Nevertheless, when the Sn doping concentration exceeds 10 mol%, the continuity of the Al2O3 layer is destroyed, thereby impairing the oxidation resistance of Ti3AlC2. Furthermore, oxidation experiments verify the above results. The oxidation mechanisms of Ti3AlC2 with different Sn doping concentrations are also proposed.
RESUMO
In esthetic rehabilitation, methods used to enhance the margin quality have always been the focus and difficulty of improving the level of diagnosis and treatment, prevention and treatment of complications, and collaboration between clinicians and technicians. However, it is impeded by the ambiguous definition and classification of margin, unstandardized tooth preparation, manufacturing process of restoration, and lack of reliable means of checking the quantitative requirements of preparation or restoration. The digital technologies that are increasingly applied, such as intra-oral scanner, impression scanner, and computerized numerical control cutting machine, have strict requirements about margin quality. Failure of recognizing margins by these scanners will hinder the digital process of diagnosis and treatment. Even if these sharp and narrow margins are successfully scanned, they cannot be milled accurately. To overcome these problems, this article demonstrated the clear and complete definition of preparation margin and restoration margin, as well as their subclassifications, by analyzing the target restoration space from a geometric perspective. Practical approaches to measuring the margin width and inspecting the margin quality were proposed. The new and full understanding and proposal about preparation margin and restoration margin characterized by measurements will effectively support the thoroughly digitalized process of esthetic rehabilitation using porcelain in fixed prosthodontics, which is based on the guidance of values.