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@#After years of development, the advantages of computer-assisted orthognathic surgery have been widely recognized. However, the clinical application of this technology is challenging. Each step may generate errors from data acquisition, computer-assisted diagnosis, and computer-assisted surgical design, causing errors to be transferred from the virtual surgical plan to the operation. The accumulation and amplification of errors will affect the final surgical effect. Currently, digital devices, such as intraoral scanners, are being explored for error control, utilizing automation methods and algorithms, and implementing personalized bone positioning methods. Moreover, there are still many problems that have not been fully resolved, such as precise simulation of postoperative soft tissue, functional assessment of mandibular movement, and absorbable internal fixation materials. Fully understanding computer-assisted orthognathic surgery's limitations could provide direction for optimizing existing methods while helping clinicians avoid risks and maximize its advantages to achieve the best outcome. Many emerging and cutting-edge technologies, such as personalized titanium plates, artificial intelligence, and surgical robots, will further promote the development of this discipline. We can expect future optimization of digital orthognathic surgical technology by innovations in automation, intelligence, and personalization.
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Objective@#To study the clinical effect of a polyetheretherketone (PEEK) bonding bridge on the loss of 3 internal incisors in patients with periodontitis.@*Methods@#This study was reviewed and approved by the ethics committee, and informed consent was obtained from the patients. Thirty-eight patients with periodontitis and 3 missing central or lateral teeth were selected to undergo restoration with a PEEK bonding bridge and then returned to the hospital 3, 6, 12, and 24 months after the restoration was completed. The survival rate of the restorations was assessed by the modified USPHS/Ryge criteria. The plaque index, gingival index, periodontal probing depth and attachment loss of the abutments were recorded, and the changes in periodontal tissues after restoration were observed and compared.@*Results@#Over 24 months of clinical follow-up observation of 38 patients, only 1 patient underwent secondary bonding after partial debonding (evaluated as grade B), while bonding was successful in the other 37 cases (evaluated as grade A). The plaque index, gingival index and periodontal probing depth were significantly lower after restoration than before (P<0.05). There was no significant change in attachment loss between before and after restoration (P>0.05).@*Conclusion@#For periodontitis patients missing 3 internal incisors, short-term PEEK bonding bridge repair has good clinical efficacy.
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Objective@#To explore an accurate method to obtain an intraoral model of patients with specific limited mouth opening (microstomia) due to systemic scleroderma.@*Methods@#This study followed medical ethics, and informed consent has been obtained from patients. A case of Ken's Type I mandibular dentition defect scleroderma with limited mouth opening was addressed with digital technology as the leading method combined with the traditional impression method of segmental impression. Individual trays were made based on the patient's left and right mandibular dentition, and segmented molds were obtained. Simultaneously, intraoral scanning was performed to obtain the morphological data of both the soft and hard tissues of the upper and lower mandibles. After each part of the model was obtained, the mandibular model was scanned and digitally aligned to form the final denture model, and the final removable partial denture was designed and made by computer aided design/computer aided manufacturing (CAD/CAM) technology. At the same time, combined with the literature, the diagnosis and treatment of removable partial denture in patients with limited mouth opening were retrospectively analyzed.@*Results@#The denture was well retained and achieved a good repair effect. The patients expressed satisfaction with the mastication efficiency and other functions of the denture. The findings of the literature review show that the integration of digital technology with the traditional impression method, along with computer fitting, can accurately obtain the patient's oral model and facilitate successful follow-up repairs. However, when the anterior mandibular dentition of the patient is absent, the margin of error is increased in this procedure, which deserves further exploration.@*Conclusion@#Utilizing digital technology as the leading method, combined with the traditional impression method of segmental impression, for the repair of dental defects in patients with limited mouth opening, has proven to be effective. Thus, patients report a positive medical experience with high satisfaction, indicating that this approach is worthy of clinical promotion.
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ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in "aspect ratio" were 95.6%, 96.2%, and 95.4%, in "margin irregularity" were 90.7%, 90.5%, and 90.9%, in "margin smoothness" were 85.8%, 88.5%, and 83.0%, in "calcification" were 83.6%, 81.7%, and 82.0%, in "homogeneity" were 88.9%, 90.6%, and 82.2%, in "major echo" were 85.3%, 88.0%, and 85.4%, and in "contains very hypoechoic echo" were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.
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Abstract To evaluate the microtensile bond strength (µTBS) of two resin cements to 3D printed and milled CAD/CAM resins used for provisional fixed partial dentures. Blocks (5 x 5 x 5 mm) of three 3D-printed resins (Cosmos3DTemp / Yller; Resilab3D Temp / Wilcos and SmartPrint BioTemp, / MMTech) were printed (Photon, Anycubic Technology Co.). A milled material (VitaCAD-Temp, VITA) was used as control. Half the specimens were sandblasted and the rest were untreated. Two blocks were bonded with the corresponding resin cement: PanaviaV5 (Kuraray Noritake) and RelyX Ultimate (3M Oral Care). After 24 hours, the bonded blocks were sectioned into 1 x 1 mm side sticks. Half the beams were tested for µTBS and the other half was thermocycled (5000 cycles, 30s dwell-time, 5s transfer time) before µTBS testing. A four way Generalized Linear Model (material*sandblasting*cement*aging) analysis was applied. VITA exhibited the lowest µTBS, regardless of the cement, sandblasting and thermocycling. Sandblasting significantly improved the µTBS of VIT, especially after aging, but did not improve the µTBS of 3D printed resins. Sandblasting was not beneficial for 3D printed resins, although is crucial for adhesive cementation of milled temporary resins. Airborne particle abrasion affects the integrity of 3D-printed resins, without producing a benefit on the microtensile bond strength of these materials. However, sandblasting is crucial to achieve a high bond strength on milled temporary resins.
Resumen Evaluar la resistencia adhesiva en microtracción (µTBS) de dos cementos resinosos a resinas CAD/CAM impresas y fresadas indicadas para restauraciones provisionales. Bloques (5 x 5 x 5mm) de tres resinas impresas (Cosmos3DTemp / Yller; Resilab3D Temp / Wilcos and SmartPrint BioTemp, / MMTech) y una resina fresada (VitaCAD-Temp, VITA) fueron fabricados. La mitad de los especímenes fueron arenados y el resto no recibió tratamiento mecánico. Dos bloques con condiciones de tratamiento iguales fueron cementados con cemento resinoso (PanaviaV5 / Kuraray Noritake y RelyX Ultimate / 3M Oral Care). Después de 24 horas los bloques fueron seccionados en palitos de 1 mm² de área. En la mitad de los especímenes se midió la TBS inmediatamente y el resto fue termociclado (5000 ciclos, 30s remojo, 5s transferencia) antes de la prueba de TBS. Se aplica un análisis estadístico por Modelo Linear General con 4 factores (material*arenado*cemento*termociclado). La resina VITA presentó la menor µTBS, independientemente del cemento usado, el arenado y el termociclado. Sin embargo, el arenado aumentó la µTBS de VIT, especialmente después del termociclado. Por otro lado, el arenado no resultó en un aumento significativo de la µTBS de las resinas impresas. El arenado no fue beneficiosos para las resinas impresas, aunque es un paso crucial para la cementación adhesive de las resinas fresadas. El arenado afecta la integridad de las capas de las resinas impresas, sin generar un beneficio en la TBS.
Sujets)
Conception assistée par ordinateur/instrumentation , Céments résine/usage thérapeutique , Cément dentaire , Impression tridimensionnelle/instrumentationRésumé
La tecnología CAD/CAM es una forma innovadora relacionada con la implementación de técnicas digitales para mejorar las restauraciones prostéticas en un paciente, entre ellas, las destinadas a la estética dental. El presente estudio tiene el objetivo de describir la utilidad de la tecnología CAD/CAM en la fabricación de prótesis dentales. Para ello se realizó una revisión de la literatura médica disponible en las bases de datos PubMed/Medline, Scopus y SciELO, mediante fórmulas de búsqueda avanzada; se seleccionaron artículos en idioma español e inglés. En la actualidad, con esta tecnología se ha logrado combinar estética, resistencia y precisión en la restauración directa, además de garantizarse una mayor duración y años de funcionalidad para cada una de las prótesis, coronas e implantes. La calidad de vida y satisfacción referidas por los pacientes portadores de piezas producidas con esta tecnología, es superior a las manifestadas por aquellos tratados con piezas de fabricación tradicional. El uso de técnicas de inteligencia artificial y biomateriales representará un cambio cualitativo y cuantitativo en el uso de los sistemas CAD/CAM.
CAD/CAM technology is an innovative way related to the implementation of digital techniques to improve prosthetic restorations in a patient, including those intended for dental aesthetics. The objective of this study is to describe the usefulness of CAD/CAM technology in the dental prostheses manufacture. A review of the medical literature available in the PubMed/Medline, Scopus and SciELO databases was carried out, using advanced search formulas; Articles in Spanish and English were selected. Currently, with this technology it has been possible to combine aesthetics, resistance and precision in direct restoration, in addition to guaranteeing greater duration and years of functionality for each of the prostheses, crowns and implants. The quality of life and satisfaction reported by patients wearing parts produced with this technology is higher than those reported by those treated with traditionally manufactured parts. The use of artificial intelligence and biomaterials techniques will represent a qualitative and quantitative change in the use of CAD/CAM systems.
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ABSTRACT BACKGROUND: Computer-aided diagnosis in low-dose (≤ 3 mSv) computed tomography (CT) is a potential screening tool for lung nodules, with quality interpretation and less inter-observer variability among readers. Therefore, we aimed to determine the screening potential of CT using a radiation dose that does not exceed 2 mSv. OBJECTIVE: We aimed to compare the diagnostic parameters of low-dose (< 2 mSv) CT interpretation results using a computer-aided diagnosis system for lung cancer screening with those of a conventional reading system used by radiologists. DESIGN AND SETTING: We conducted a comparative study of chest CT images for lung cancer screening at three private institutions. METHODS: A database of low-dose (< 2 mSv) chest CT images of patients at risk of lung cancer was viewed with the conventional reading system (301 patients and 226 nodules) or computer-aided diagnosis system without any subsequent radiologist review (944 patients and 1,048 nodules). RESULTS: The numbers of detected and solid nodules per patient (both P < 0.0001) were higher using the computer-aided diagnosis system than those using the conventional reading system. The nodule size was reported as the maximum size in any plane in the computer-aided diagnosis system. Higher numbers of patients (102 [11%] versus 20 [7%], P = 0.0345) and nodules (154 [15%] versus 17 [8%], P = 0.0035) were diagnosed with cancer using the computer-aided diagnosis system. CONCLUSIONS: The computer-aided diagnosis system facilitates the diagnosis of cancerous nodules, especially solid nodules, in low-dose (< 2 mSv) CT among patients at risk for lung cancer.
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Abstract This study aimed to investigate the failure behavior of 3 mol.% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) prosthetic crowns air-abraded with aluminum oxide (AO) particles of different sizes. Ninety ceramic premolar crowns were produced with 3Y-TZP frameworks veneered with porcelain. Crowns were randomly divided into three groups, according to the size of the air abrasion AO particles (n = 30): (GC) untreated (control); (G53) 53 µm; (G125) 125 µm. Air abrasion was performed with 0.25 mpa pressure, 10-mm distance, for 10 s. Crowns were adhesively cemented to dentin analog abutments. Specimens were loaded in compression to failure, in 37oC distilled water, using a universal testing machine (n = 30). Fractographic analysis was performed using a stereomicroscope and SEM. The roughness of the crown's inner surface was evaluated using an optical profilometer (n = 10). Fracture load data were statistically analyzed with Weibull analysis and roughness data with Kruskal-Wallis (α = 0.05). GC had the lowest characteristic fracture load (L0), while G53 and G125 had higher and statistically similar L0 values. The Weibull modulus (m) was similar among groups. The failure modes observed were catastrophic failure and porcelain chipping. There were no differences between the roughness parameters for the experimental groups (p > 0.05). The size of the AO particles did not affect the fracture load and failure mode of 3Y-TZP crowns. Air abrasion with 53 µm and 125 µm particles resulted in a higher fracture load of ceramic crowns than the untreated group while maintaining their reliability and surface characteristics.
Resumo O objetivo deste estudo foi investigar o efeito do jateamento com óxido de alumínio (AO) com diferentes tamanhos de partículas no comportamento de fratura de coroas protéticas de zircônia tetragonal estabilizada com 3 mol% de ítria (3Y-TZP). Noventa coroas cerâmicas de pré-molares foram produzidas com infraestruturas de 3Y-TZP recobertas com porcelana. As coroas foram divididas aleatoriamente em três grupos, de acordo com o tamanho das partículas de AO do jateamento (n = 30): (GC) não tratada (controle); (G53) 53 µm; (G125) 125 µm. O jateamento foi realizado com pressão de 0,25 MPa, distância de 10 mm, por 10 s. As coroas foram cimentadas adesivamente em pilares análogos à dentina. As coroas foram testadas em compressão até a falha, em água destilada a 37ºC, usando uma máquina universal de ensaios (n = 30). A análise fractográfica foi realizada usando estereomicroscópio e MEV. A rugosidade da superfície interna das coroas foi avaliada usando um perfilômetro óptico (n = 10). Os dados de carga de fratura foram analisados estatisticamente com análise de Weibull e os dados de rugosidade com Kruskal-Wallis (( = 0,05). GC apresentou a menor carga característica de fratura (L0), enquanto G53 e G125 apresentaram valores de L0 maiores e estatisticamente semelhantes. O módulo de Weibull (m) foi semelhante entre os grupos. Os modos de falha observados foram falha catastrófica e lascamento da porcelana. Não houve diferenças entre os parâmetros de rugosidade para os grupos experimentais (p > 0,05). O tamanho das partículas de AO não afetou a carga de fratura e o modo de falha das coroas 3Y-TZP. O jateamento com partículas de 53 µm e 125 µm resultou em maior carga de fratura das coroas cerâmicas do que o grupo não tratado, mantendo sua confiabilidade e características de superfície.
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Objective To investigate the effects of banding width on hemodynamic characteristics of pulmonary artery (PA) by constructing pulmonary artery banding (PAB) models with different widths. Methods Based on clinical practice, with the same banding position and degree, computer-aided design (CAD) was utilized to reconstruct three-dimensional PAB models with different banding widths (2, 3, 4, 5 mm). Hemodynamic characteristics of the models with different banding widths, including pressure, streamlines, energy loss, energy efficiency and blood flow distribution ratio, were compared and analyzed through computational fluid dynamics (CFD). Results The pressure of PA decreased significantly, while the change of banding width had no significant effects on the pressure drop level at banding position. With the increase of banding width, the energy loss decreased, and the energy efficiency showed an upward trend. The blood flow of the left PA raised, and the ratio of blood flow distribution between the left PA and right PA increased, with the maximum reaching up to 2.28 : 1. Conclusions The increase of banding width can reduce the energy loss of PA and improve the energy efficiency of blood flow, but it will lead to the imbalance of blood flow distributions between the left and right lungs. Both the balance of blood flow distribution and the energy loss should be considered in choice for banding width of PAB. The virtual design of PAB surgery based on CAD and CFD will assist individualized banding width selection in future.
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@#Artificial intelligence (AI) has developed rapidly in the twentieth century, and has substantialy changed the modern way of life.At the same time, AI has greatly contributed to the development of the pharmaceutical industry, playing a key role in precision medicine, intelligent diagnosis, computer-aided drug design, and clinical trial decision-making, and has also greatly developed itself through its integration with the pharmaceutical industry.This paper outlines the key issues in research, describes the key applications of AI in the health and pharmaceutical industries, and finally analyzes the opportunities and challenges of AI in the health pharmaceutical industry to provide reference for the development of AI in the health and pharmaceutical fields.
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Objective:To investigate the effect of 3D-printed customized flanged cup in hip revision with severe acetabular bone defects.Methods:Since February 2017, 10 cases of 3D-printed customized flanged cups were used in hip revision with severe acetabular bone defects, including 2 cases of Paprosky type IIIA and 8 cases of Paprosky type IIIB. There were 5 males and 5 females, mean age 73.6±8.1 yrs (range, 62-87 yrs), 5 left and 5 right cases. The preoperative thin-layer CT scan was preformed to reverse reconstruct digital pelvis. Five cases of one-piece flanged cups and 5 cases of decomposed flanged cups, including 3 cases of composite one-piece cups were designed by computer. The surgery was performed strictly according to the plan.Postoperative follow-up was performed to evaluate the Harris score. Operation time,intraoperative bleeding and other complications such as vascular and nerve injury, postoperative infection, and dislocation were counted. Pelvic X-ray was used to assess the height and horizontal position of the center of rotation and the stability of the prosthesis.Results:The surgical procedure was successful, with an average operative time of 147.9±48.3 min (range, 96-212 min) and an average intraoperative bleeding of 730.4±262.6 ml (range, 500-1 300 ml). The mean time of final follow-up was 40.8±18.7 months (range, 16-70 months) after surgery. At the last follow-up, the average Harris score was 83.80±6.73, with 4 cases excellent, 5 cases good, and 1 case fair. The excellent and good rate was 90%. The last Harris score was significantly higher than that before operation 28.60±8.40 ( t=16.84, P<0.001). The height of affected hip joint rotation center decreased from 46.24±7.74 mm before operation to 15.54±2.54 mm after operation with significant difference ( t=14.61, P<0.001). It was slightly higher than the opposite side (13.81±1.48 mm), which had no significant difference ( t=1.83, P=0.100). The horizontal distance of affected hip joint rotation center increased from 33.79±5.27 mm before operation to 40.53±4.50 mm after operation with significant difference ( t=3.62, P=0.006). It had no significant difference ( t=1.28, P=0.232) compared with the opposite side (38.54±3.46 mm). All incisions were healed in one stage without infection, vascular or nerve injury. During the following-up, all prostheses were in satisfied position without loosening, dislocation or screw breaks. Conclusion:Digitally assisted 3D-printed flanged cups can be used in hip revision with severe acetabular bone defect. It can not only improve hip joint function, but also restore the acetabular rotation center and the prosthesis stability, which can achieve good early and mid-term effect.
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Objective:To evaluate the efficacy of 3D printed patients-specific guide plates in assisting Ilizarov bone transport in the treatment of tibial bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 24 patients with tibial bone defects who had been admitted to Institute of Trauma Orthopedics, The 80th Army Group Hospital of PLA from January 2018 to March 2022. There were 9 males and 15 females with an age of (49.8±6.5) years, and 4 upper tibial defects, 5 middle tibial defects, and 15 lower tibial defects. According to the methods of repairing bone defects, the patients were divided into 2 groups: a 3D printing group of 10 cases where a 3D printed patient-specific guide plate was used to assist Ilizarov bone transport in the treatment of tibial bone defects, and a traditional group of 14 cases where Ilizarov bone transport was performed in a traditional manner. The 2 groups were compared in terms of operation time, frequency of intraoperative fluoroscopy, axial angulation of the tibia at postoperation and the last follow-up, external fixation time (EFT) and external fixation index (EFI). At the last follow-up, healing of bone defects was evaluated according to the criteria of The Association for the Study and Application of the Method of Ilizarov (ASAMI), functional outcomes were evaluated according to the Paley criteria, and needle infection was recorded according to the Paley classification for complications.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (11.3±2.0) months on average after operation. The 3D printing group had significantly shorter operation time [(19.9±2.6) min] and significantly lower frequency of intraoperative fluoroscopy [(3.0±0.8) times] than the traditional group [(38.1±2.2) min and (8.9±1.3) times] (P<0.05), and had significantly better axial angulation of the tibia at postoperation and the last follow-up than the traditional group ( P<0.05). There was no significant difference in EFT or EFI between the 2 groups ( P>0.05), and the last follow-up revealed no significant difference either in bone healing, functional outcomes, or needle infection between the 2 groups ( P>0.05). Conclusion:In the treatment of tibial bone defects, compared with conventional Ilizarov bone transport, the Ilizarov bone transport assisted by a 3D printed patient-specific guide plate demonstrates advantages of shorter operation time, lower intraoperative fluoroscopy, and higher reduction accuracy.
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Objective:To design an anatomical plate of ulna coronoid process using 3D printing and computer model design software based on a collection of CT scanning data of the ulna coronoid process.Methods:The CT scans of the elbow joint with no obvious anatomic variation, no fracture, or no history of elbow operation were collected which had been taken at Trauma Center, The First Affiliated Hospital of Kunming Medical University from September 2017 to January 2022. There were 52 males and 50 females. RadiAnt DICOM Viewer and Mimics Medical 21.0 were used to visualize the CT data of the elbow joint of 102 volunteers. The software was used to measure the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, and the safety angle for screw placement. After the values were measured, Siemens Ungraphics NX12.0 software was used to design the anatomical plate and the screw guide device of the ulna coronoid process. After the plate model was designed, a 1:1 actual plate model of the ulna coronoid process was produced by 3D printing. The actual plate model was placed onto an adult model of the ulna coronoid process and an adult cadaveric specimen of the ulna coronoid process to verify its matching degree. An in vitro operation was simulated using the plate model to verify its operability. Results:There were no significant differences between the left and right sides in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna, the width at 1/2 height of the ulna coronoid process, the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity, or the safety angle for screw placement in either males or females ( P>0.05). There were no significant differences between males and females in the angle between the tip of the ulna coronoid process and the tuberosity of the ulna or in the safety angle for screw placement ( P>0.05). There were statistically significant differences between males and females in the width of 1/2 height of the ulna coronoid process and the distance between the tip of the ulna coronoid process and the horizontal plane of the ulna tuberosity ( P<0.05). However, the experiments on computer simulative adaptation and plate model simulative adaptation found that the anatomical plates of the ulna coronoid process designed on various parameters of males and females were exchangeable, leading to similarly good marching degrees and safe angles for screw placement. Conclusions:The anatomical plate of the ulna coronoid process designed in this study demonstrates a good fit and a safe angle for screw placement, basically achieving the goal expected to provide a basis for fabrication of a titanium alloy plate. In design of an anatomical plate of ulna coronoid process, it is not necessary to differentiate males from females or to differentiate the left side from the right one, because only a general plate can be used for both males and females and for both the left and the right sides.
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In recent years, artificial intelligence-related technologies have been deeply combined with many medical fields, and the intersection of medicine and engineering has become a hot topic. There are problems with heavy data and difficulty making decisions in orthopedic disease diagnosis and treatment. Machine learning is an important method of artificial intelligence. Since it can automatically analyze and predict medical big data, it is widely used in the field of orthopedics. It also assists physicians in completing disease diagnosis and treatment efficiently. In this review paper, the application and progress of machine learning in preoperative, intraoperative, and postoperative diagnosis and treatment in orthopedics are reviewed, providing new ways for exploring more rational diagnosis and treatment strategies.
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Artificial intelligence-aided drug discovery (AIDD) is a new version of computer-aided drug discovery (CADD). AIDD is featured in significantly promoting the performance of conventional CADD. AI markedly enhances the learning ability of CADD. In the 1960s, CADD was established from conventional QSAR approaches, which mainly used regression approaches to derive substructure-activity relationship for compounds with a common scaffold, and guide drug molecular design, figure out the binding features of drugs, and identify potential drug targets. Since the 1990s, structural biology has provided three-dimensional structures of drug targets, enabling drug discovery based on target structure (SBDD), fragment-based drug discovery (FBDD), and structure-based virtual screening (SBVS) with CADD approaches. In the past 30 years, many first in class (FIC) and best in class (BIC) drugs were discovered with CADD. Now, AIDD will further revolutionize CADD by reducing human interventions and mining big chemical and biological data. It is expected that AIDD will significantly enhance the abilities of CADD, virtual screening and drug target identification. This article tries to provide perspectives of CADD and AIDD in medicinal chemistry with case studies.
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In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl2 was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L-1 CoCl2 for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.
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The binding of small molecule drugs to targets is mostly through non-covalent bonds, and hydrogen bond, electrostatic, hydrophobic and van der Waals interactions function to maintain the binding force. The more these binding factors lead to strong bindings and high activities. However, it is often accompanied by the increase of molecular size, resulting in pharmacokinetic problems such as membrane penetration and absorption, as well as metabolism, which ultimately affects the drug success. Fragment-based drug discovery (FBDD) is to screen high-quality fragment library to find hits. Combine with structural biology, FBDD generates lead compounds by means of fragment growth, linking and fusion, and finally drug candidates by the optimization operation. During the value chain FBDD is closely related to structure-based drug discovery (SBDD). In this paper, the principle of FBDD is briefly described by several launched drugs.
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In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.
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@#With the development of computer-aided surgery and rapid prototyping via 3D printing technology, digital surgery has rapidly advanced in clinical practice, especially in the field of oral and maxillofacial surgery. 3D printing technology has been applied to the functional restoration and reconstruction of the jawbone. Before surgery, a 3D digital model is constructed through software to plan the scope of the osteotomy, shape the bone graft and plan the placement of the implant. Additionally, 3D models of personalized surgical instrument guides are printed prior to surgery. With these 3D-printed models and guides, accurate excision of the jaw tumor, accurate placement of the grafted bone and precise placement of implants can be achieved during surgery. Postoperative evaluation of accuracy and function shows that 3D printing technology can aid in achieving the biomechanical goals of simultaneous implant placement in jaw reconstruction, and in combination with dental implant restoration, the technology can improve patients' postoperative occlusal and masticatory functions. Nevertheless, 3D printing technology still has limitations, such as time-consuming preparation before surgery. In the future, further development of 3D printing technology, optimization of surgical plans, and alternative biological materials are needed. Based on domestic and foreign literature and our research results, we have reviewed the process and clinical application prospects of jaw reconstruction via 3D printing technology to provide a reference for oral and maxillofacial surgeons.
Résumé
With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.