Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

Objective:To establish and validate a gallstones classification method based on deep learning.Methods:A total of 618 gallstones samples were collected from East Hospital Affiliated to Tongji University, and 1 023 high-definition cross-sectional gallstones profile images were captured to construct a cross-sectional gallstones profile image dataset. Based on the traditional eight-category gallstones classification method, a lightweight network model, MobileNet V3, was trained using deep learning and transfer learning methods. The classification performance of MobileNet was evaluated using a confusion matrix with metrics such as accuracy rate, precision rate, F1 score, and recall rate. The MobileNet V3 was improved and further validated using accuracy and loss values.Results:The accuracy rate (94.17%), precision rate (94.03%), F1 score (92.96%) and recall rate (92.99%) of the improved MobileNet V3 model were better than other networks. The improved MobileNet V3 model achieved the highest accuracy rate (94.17%) in gallstones profile classification and was validated by the test set. The confusion matrix showed a weighted average of accuracy rate (92.0%), precision rate (92.6%), and F1 score (92.2%) for each category of gallstones.Conclusions:Based on deep learning, a high-accuracy gallstones classification method is proposed, which provides a new idea for the intelligent identification of gallstones.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

The Internet has become an important carrier of medical information.Good electronic health literacy can enhance the public’s ability to obtain correct medical and health information with the help of electronic resources,which is helpful for the public to use health information to prevent diseases,avoid drug abuse,reduce the waste of medical resources and strengthen the self-management of chronic diseases.The improvement of electronic health literacy is of great value to the healthy development of citizens’ health literacy and healthy behavior.In view of the late start and slow development in the field of electronic health literacy in China,by combing the theoretical and practical research experience of electronic health literacy outside the region and combining with the COVID-19,this paper put forward new thinking on electronic health literacy in China,in order to provide useful reference for improving electronic health literacy of Chinese citizens,realizing self-care,self-management and disease prevention.

Objective To develop and validate a deep learning model for automatic identification of liver CT contrast-enhanced phases.Methods A total of 766 patients with liver CT contrast-enhanced images were retrospectively collected.A three-phase classification model and an arterial phase(AP)classification model were developed,so as to automatically identify liver CT contrast-enhanced phases as early arterial phase(EAP)or late arterial phase(LAP),portal venous phase(PVP),and equilibrium phase(EP).In addition,221 patients with liver CT contrast-enhanced images in 5 different hospitals were used for external validation.The annotation results of radiologists were used as a reference standard to evaluate the model performances.Results In the external validation datasets,the accuracy in identifying each enhanced phase reached to 90.50%-99.70%.Conclusion The automatic identification model of liver CT contrast-enhanced phases based on residual network may provide an efficient,objective,and unified image quality control tool.

BACKGROUND:Bone tissue remodeling is closely related to stress loading.Currently,there are few studies or guidelines on the relationship between bone and occlusal adjustment of implant prostheses and there is also a lack of scientific evidence. OBJECTIVE:To investigate the effects of different implant occlusal gaps on stress distribution,stress peak and displacement at the implant-bone interface under Ⅰ-Ⅳ bone conditions by a finite element method. METHODS:After scanning the equal-scale tooth model with an optical scanner,equal-scale models of the upper right first molar Straumann 4.8×8 mm BL RC implant and its related components was constructed using Solidworks 2022.Then,using Mimics,Geomagic,and Solidworks software,the maxillary and mandibular bone models of class Ⅰ-Ⅳ bones were established based on the bone classification proposed by ZARB and LEKHOLM in the literature,and the NORTON and TRISI bone density classification method.The models were assembled with the occlusal gaps of 0,20,40,60,80,and 100 μm for the restorations,and an additional set of homogeneous models without density ratio settings was constructed for comparison.After the above models were imported into Hypermesh for meshing,the material assignment,boundary constraints and parameter setting were performed for the finite element analysis.Finally,250 N was used as the loading force to simulate the maxillary and mandibular stress conditions.Stress distribution,peak stress and displacement of the implant-bone interface in each group of models were analyzed and compared. RESULTS AND CONCLUSION:Under the same loading conditions,the stresses in the implant restorations were evenly distributed with the occlusal contact points.When the occlusal gap reached 80 and 100 μm,stress interruptions occurred in the implant crowns under class Ⅰ bone and class Ⅱ,Ⅲ and Ⅳ bones,respectively.The displacement of the implant-bone interface was mainly concentrated in the cortical bone region around the implant and transmitted down the long axis of the implant to the cancellous bone region at the bottom.With the changes of class Ⅰ-Ⅳ jaw bones,the displacement and Von Mises stress in the cortical bone region increased in all groups,and were greater than those in the cancellous bone region.The Von Mises stress in the cancellous bone region was similar to that in the cortical bone region except that it showed a downward trend from class Ⅱ bone.However,when the occlusal gap increased,the stress and displacement peak values in the cortical bone and the cancellous bone showed a decreasing trend.The stress of the implant-bone interface was between 20 MPa and 60 MPa when the occlusal gap was 0-40 μm for class Ⅱ-Ⅳ bones and 60 μm for class Ⅳ bone,and the stress of the other groups was less than 20 MPa.The Von Mises stress was mainly concentrated in the neck of the implant,and the peak value of von Mises stress in class Ⅱ-Ⅳ bones with the occlusal gap of 20 μm was higher than that(144.10 MPa)in class Ⅰ bone with the occlusal gap of 0 μm.In the homogeneous model with different elastic moduli,the distribution of stress and displacement was more uniform than that in the heterogeneous model and the occlusal space should increase with the decrease of jaw bone density in clinical practice.To conclude,from the perspective of biomechanics,the alveolar bone should be taken into account in the occlusal adjustment of implant denture.An occlusal gap of 20-40 μm between a single dental implant and a natural tooth in the opposite jaw is a relatively suitable solution for occlusal adjustment under different bone conditions.However,due to the particularity of finite element analysis method,it needs to be further studied in combination with clinical practice.