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BACKGROUND@#Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but their role in OSF has received little attention. The aim of this study was to investigate the effects of ADSC-Exo on OSF and elucidate the mechanism. @*METHODS@#In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1), Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2 mRNA to regulate the transforming growth factor beta (TGF-β) pathway. We also performed qPCR and western blotting to verify the results. @*RESULTS@#ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway. @*CONCLUSIONS@#ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.
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OBJECTIVES@#With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules.@*METHODS@#We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared.@*RESULTS@#There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001).@*CONCLUSIONS@#T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.
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Adulto , Humanos , Estudios Retrospectivos , Imagen por Resonancia Magnética , Plasma , Tomografía Computarizada por Rayos X , PulmónRESUMEN
Femoral fracture is a common type of fracture in clinical practice, and poor fracture reduction may lead to malunion and dysfunction. At present, traditional reduction with manipulation and intramedullary nailing are the mainstream treatments, but there exist problems such as X-ray exposure or poor reduction. Fracture reduction robots are of positive significance in improving the safety of surgical treatment of femur fracture, avoiding repetitive operations and poor alignment, and shortening the patients′ postoperative recovery time. Navigation algorithm is the key to achieve the function of femoral repositioning. Understanding the advantages and disadvantages that various types of navigation algorithms demonstrated in femoral reduction applications is important for giving full play to the value of fracture reduction robots in femoral reduction. Therefore, the authors reviewed the research progress in existing robot navigation algorithms applied in femoral fracture repositioning from the following four aspects, including image alignment algorithm, algorithm for establishing the target pose of femoral repositioning, algorithm for compensating the mechanical error, and algorithm for path planning, hoping to provide a reference for the application and research of navigation algorithms of fracture reduction robots.
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Bone defects, often accompanied by osteomyelitis, soft tissue contusions, etc, are facing lengthy treatment process and slow healing, seriously jeopardizing the structural integrity of the human bone tissue. Currently, the main treatment for bone defects involves autologous or allogeneic bone transplant. However, autologous bone transplant poses problems, including long surgical duration, increased pain and complications such as infections. Additionally, immune rejection reactions also limit the effectiveness of allogeneic bone transplant of the same species. Bone scaffolds have become a potential alternative for bone transplant, but problems such as sharp edges of the scaffolds and poor compatibility with human tissues exist. Triply periodic minimal surface (TPMS), with an average curvature of zero has lower levels of stress concentration and the ability to be precisely expressed with mathematical formulas, compared with other structures. Its application in bone scaffolds attracts much attention, but there is currently a lack of comprehensive understanding of the impacts of different types of TPMS on the performance of bone scaffolds. With this purpose, the authors reviewed the research progress in the impacts of different types of TPMS on the performance of bone scaffolds, providing a reference for the construction of bone scaffolds.
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Orthopedic robots, as intelligent medical devices, have achieved good outcomes in clinical application in some orthopedic surgeries. Artificial intelligence (AI) has played an important role in the development of orthopedic robots due to its powerful capabilities of information processing and decision-making. The developing trends of orthopedic robotics are automation and intelligentization. Since AI has demonstrated great advantages in preoperative planning, an increasing number of researchers have been devoted to AI application in intraoperative navigation by an orthopedic robot. This paper outlines the exploratory efforts in applying AI technology to the intraoperative navigation assisted by an orthopedic robot, describes the advantages of AI in improving accuracy and reducing radiation, and forecasts research prospects in application of AI technology to orthopedic robots based on the current situation.
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OBJECTIVE@#To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide.@*METHODS@#Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR).@*RESULTS@#ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05).@*CONCLUSION@#MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.
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Femenino , Ratas , Animales , Factor de Necrosis Tumoral alfa , Osteogénesis , Ratas Sprague-Dawley , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Melatonina/farmacología , Interleucina-6/genética , Lipopolisacáridos/farmacología , Colorantes , InflamaciónRESUMEN
OBJECTIVE@#To review the research progress of design of bone scaffolds with different single cell structures.@*METHODS@#The related literature on the study of bone scaffolds with different single cell structures at home and abroad in recent years was extensively reviewed, and the research progress was summarized.@*RESULTS@#The single cell structure of bone scaffold can be divided into regular cell structure, irregular cell structure, cell structure designed based on topology optimization theory, and cell structure designed based on triply periodic minimal surface. Different single cell structures have different structural morphology and geometric characteristics, and the selection of single cell structure directly determines the mechanical properties and biological properties of bone scaffold. It is very important to choose a reasonable cell structure for bone scaffold to replace the original bone tissue.@*CONCLUSION@#Bone scaffolds have been widely studied, but there are many kinds of bone scaffolds at present, and the optimization of single cell structure should be considered comprehensively, which is helpful to develop bone scaffolds with excellent performance and provide effective support for bone tissue.
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Huesos , Andamios del TejidoRESUMEN
OBJECTIVE@#To summarize the influence of microstructure on performance of triply-periodic minimal surface (TPMS) bone scaffolds.@*METHODS@#The relevant literature on the microstructure of TPMS bone scaffolds both domestically and internationally in recent years was widely reviewed, and the research progress in the imfluence of microstructure on the performance of bone scaffolds was summarized.@*RESULTS@#The microstructure characteristics of TPMS bone scaffolds, such as pore shape, porosity, pore size, curvature, specific surface area, and tortuosity, exert a profound influence on bone scaffold performance. By finely adjusting the above parameters, it becomes feasible to substantially optimize the structural mechanical characteristics of the scaffold, thereby effectively preempting the occurrence of stress shielding phenomena. Concurrently, the manipulation of these parameters can also optimize the scaffold's biological performance, facilitating cell adhesion, proliferation, and growth, while facilitating the ingrowth and permeation of bone tissue. Ultimately, the ideal bone fusion results will obtain.@*CONCLUSION@#The microstructure significantly and substantially influences the performance of TPMS bone scaffolds. By deeply exploring the characteristics of these microstructure effects on the performance of bone scaffolds, the design of bone scaffolds can be further optimized to better match specific implantation regions.
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Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Huesos , PorosidadRESUMEN
Objective:To investigate the quality of life in patients with early-stage extra-nodal NK/T cell lymphoma of nasal type (ENKTL) arising from the upper aerodigestive tract, who had remained progression-free survival (PFS) for over 3 months after definitive intensity-modulated radiation therapy (IMRT), and to analyze the factors related to main adverse symptoms.Methods:276 patients who received IMRT from March, 2012 to June, 2021 were included. There were 201 males and 75 females with a median age of 41.5 years (range: 13-81 years) upon diagnosis. Consistent target delineation schemes and similar dose gradients were adopted for IMRT, with a median prescribed dose of 54.6 Gy/26F. Cross-sectional investigation was performed with a modified EORTC QLQ-H&N35 questionnaire, the incidence and severity of adverse symptoms, severity of disease and their influencing factors at each time-point during their survival were statistically analyzed.Results:The median age of patients at the investigation was 46.2 years, and the median PFS after IMRT was 47.2 months (range: 3.1-115.7 months). The most common adverse symptoms included nasal symptoms (incidence rate 63.8%), dry mouth (50%), tooth diseases (47.1%), smell and taste alteration, and sexual apathy, etc. Most symptoms were mild (the average standardized score was 5.50, the full score of 100 indicating the most severe), and could be relieved remarkably over survival time, but some symptoms, such as tooth diseases and sexual apathy, were more obvious and recurred for several years. Age and anti-PD-1 immune therapy influenced the symptom scores, and tooth diseases were closely correlated with dry mouth. Conclusion:The quality of life in patients with early-stage ENKTL after definitive IMRT is high, and the most significant symptoms include nasal symptoms, tooth diseases, and sexual apathy, etc. , which need to be mitigated with more studies.
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Objective To retrospectively analyze the prognostic factors for locoregionally recurrent early?stage extranodal nasal?type natural killer/T?cell lymphoma ( NKTCL) . Methods A total of 56 patients with early?stage extranodal nasal?type NKTCL, who had locoregional recurrence after initial treatment and then received salvage treatment from 1995 to 2014, were enrolled as subjects. The effects of salvage treatment on the overall survival ( OS) rate were analyzed after initial treatment and recurrence. Univariate and multivariate prognostic analyses were performed on the OS rate after recurrence. Results The median follow?up time was 35. 9 months after initial treatment and 14. 8 months after recurrence. The 3?year OS rate was 73% after initial treatment and 58% after recurrence. Compared with chemotherapy alone, radiotherapy?containing salvage treatment significantly improved the OS rates after initial treatment and recurrence ( P=0. 040, 0. 009 ) , and re?irradiation also significantly improved the OS rates after initial treatment and recurrence (P=0. 018, 0. 019). Most (84%) of the acute and late adverse reactions after re?irradiation were grade 1?2 ones. The univariate and multivariate analyses showed that the Karnofsky Performance Status score, radiotherapy in initial treatment, and radiotherapy in salvage treatment were influencing factors for the OS rate after recurrence. Conclusions Radiotherapy achieves improved survival and tolerable toxicities, making it indispensable in the treatment of locoregionally recurrent extranodal nasal?type NKTCL.
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Objective To analyze the clinical features,treatment methods,and prognostic factors for early primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.Methods A retrospective analysis was performed on the clinical data,treatment outcomes,and survival of 32 patients with early pulmonary MALT lymphoma from March 2001 to September 2013.The median age of those patients was 56 years.Twenty-three patients had stage ⅠE disease and nine had stage Ⅱ E disease.According to the marginal zone B-cell lymphoma prognostic index (MZLPI),twenty-three patients were scored as 0 and nine as 1.Nine patients received radiotherapy,eight patients underwent surgery alone,three patients underwent surgery plus chemotherapy,and twelve patients received chemotherapy alone.The Kaplan-Meier method was adapted for calculating the OS,PFS and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 5-year sample size was 22.The 5-year overall survival (OS) and progression-free survival (PFS) rates were 84.5% and 73.2%,respectively.Radiotherapy yielded an overall response rate of 100%,including a complete response rate of 66.7% and a partial response rate of 33.3%.The univariate analysis showed that non-radiotherapy treatment was a prognostic factor for poor PFS.The patients treated with radiotherapy had significantly higher 5-year PFS rates than those treated without radiotherapy (100% vs.63.0%,P=0.029),while there was no significant difference in 5-year OS rate between these two groups (100% vs.78.8%,P=0.129).Age older than 60 years,an ECOG score of 2,and an MZLPI score of 1 were prognostic factors for poor PFS (P=0.041,0.018,and 0.044) and OS (P=0.001,0.001,and 0.003).Conclusions The prognostic factors for early pulmonary MALT lymphoma include age,ECOG score,and MZLPI score.Low-dose involved-field radiotherapy (24-30 Gy) can improve local control and survival.
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Objective To investigate the feasibility of the scheme of target volume delineation with extended involved?field intensity?modulated radiotherapy (IMRT) for patients with early?stage nasal NK/ T?cell lymphoma (NC?NKTL). Methods Twenty?one patients with stage IE?IIE NC?NKTL were treated with short?course chemotherapy combined with radiotherapy from 2011 to 2013. The majority of patients received the GELOX regimen. All patients received extended involved?field IMRT with a dose of 54?? 6 Gy in 26 fractions for gross tumor volume, 50?? 7 Gy in 26 fractions for high?risk clinical target volume (CTV), and 45?? 5 Gy in 26 fractions for low?risk CTV. The dose distribution, short?term treatment outcomes, and adverse reactions were analyzed. Results The 2?year sample size was 12. The 2?year follow?up rate was 100%. The 2?year local control rate ( LRC) was 100%. The 2?year overall and progression?free survival rates were 90?? 5% and 90?? 5%, respectively. The median coverage rates of planning target volumes with 90% of the prescribed doses of 54?? 6 Gy, 50?? 7 Gy, and 45?? 5 Gy were 99?? 8%, 99?? 6%, and 99?? 7%, respectively. No grade 3 or 4 adverse reactions were observed in patients. Conclusions The scheme of target volume delineation and dose configuration in our study not only achieves excellent target volume coverage, but also reduces adverse reactions in patients, which achieves a 2?year LRC ideal for patients with early?stage NC?NKTL.
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Objective:o prepare Danshensu liposomes and investigate drug release characteristics in vitro. Methods: Danshensu liposomes were prepared by a reverse-phase evaporation method. The encapsulation efficiency was used as the index, an orthogonal test was adopted to investigate the effect of concentration of soybean lecithin, ratio of lipid-Danshensu and pH value of solution on the preparation procedure of Danshensu liposomes. The particle size of the liposomes was also investigated by a transmission electron micro-scope ( TEM) . The concentration of Danshensu was determined by HPLC, and the difference of release characteristics in Danshensu li-posomes and Danshensu solution was measured by a dialysis method. Results:The optimum preparation technology was as follows:the concentration of soybean lecithin was 40 mg·ml-1 ,the ratio of drug-lipid was 1: 10,and the pH value of solution was 6. 6. The mor-phology of the prepared liposomes showed spheric structure with uniform diameter, and the average particle size was ( 174 ± 36 ) nm and the encapsulation efficiency was 38. 9%. The linear range of Danshensu was 2. 0-20. 0 mg·L-1(r=0. 9984). The drug release of liposomes in vitro was slower than that of free Danshensu solution in 24 h. Conclusion:Danshensu liposomes with fine morphology have sustained release property.
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Objective To explore the predictive value of primary tumor site for loco?regional recurrence ( LRR) in early breast cancer patients with one to three positive axillary lymph nodes after radical surgery. Methods The clinical data of 656 patients pathologically diagnosed with pT1?2 N1 M0 breast cancer who received radical surgery without postoperative radiotherapy in our hospital from 1998 to 2010 were retrospectively analyzed. In those patients, 156 had primary tumor located in the inner quadrant, 45 in the central quadrant, and 455 in the outer quadrant. LRR and local recurrence?free survival ( LRFS) were end points. The Kaplan?Meier method was used to estimate LRR and LRFS rates. The log?rank test was used for survival difference analysis and univariate prognostic analysis. Multivariate analysis was performed using the Cox regression model. Results The 5?and 10?year sample sizes were 416 and 191, respectively. The 5?and 10?year LRR rates were 8?6% and 12?9%, respectively, while the 5?and 10?year LRFS rates were 86?2%and 76?4%, respectively. The univariate analysis indicated that age, pT stage, Ki67 level, molecular classification, and primary tumor in the inner quadrant were significant influencing factors for LRR ( P=0?000,0?006,0?017,0?004,0?000). The multivariate analysis showed that age no greater than 35 years, primary tumor in the inner quadrant, and non?luminal subtype in molecular classification were independent prognostic factors for LRR and LRFS ( P=0?0012,0?012,0?005) . With an increasing number of risk factors ( ≥ 2 ) , patients with primary tumor in the inner quadrant had a dramatically increased LRR rate and a reduced LRFS rate, while patients with primary tumor in the outer or central quadrant kept the same LRR and LRFS rates. Conclusions The primary tumor site holds promise for prediction of LRR and LRFS in patients with pT1?2N1M0 breast cancer after radical surgery. Patients with primary tumor located in the inner quadrant have a high LRR rate and a low LRFS rate, which provides an excellent predictor for the risk of recurrence in patients with high?risk breast cancer.