BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

This article retrospectively analyzed the involvement of clinical pharmacists in the treatment process and implementation of pharmacological supervision in a patient with septic arthritis secondary to tophi ulceration.The patient was admitted to the hospital and the emergency debridement and tophi removal were performed.Piperacillin-tazobactam,imipenem cilastatin,levofloxacin,linezolid,and vancomycin were given successively,and multiple debridement and drainage were performed,but the patient remained febrile and had recurrent infection indicators.According to the relevant guidelines and evidence-based evidence,combined with the patient's infection indicators,pathogen results and creatinine clearance rate,the clinical pharmacists recommended stopping vancomycin and changing to cefazolin,and the clinicians adopted it.After that,the patient's inflammatory indicators gradually decreased,and the body temperature stabilized.After 28 days of piperacillin-tazobactam administration,the patient developed a reduction in white blood cell count(2.34×109·L-1)and potassium(2.98 mmol·L-1).The pharmacist recommended prompt discontinuation of the drug,and the patient's white blood cell count and potassium gradually recovered.Eventually,after anti-infective treatment and surgical intervention,the patient was discharged with closure of the infected foci,conversion of multiple blood cultures to negative,and stabilisation of body temperature and renal function.This case reflects the role of clinical pharmacists in the management of drug treatment of critically ill patients,and may provide practical experience and reference for clinical treatment of such cases.

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.

This article retrospectively analyzed the involvement of clinical pharmacists in the treatment process and implementation of pharmacological supervision in a patient with septic arthritis secondary to tophi ulceration.The patient was admitted to the hospital and the emergency debridement and tophi removal were performed.Piperacillin-tazobactam,imipenem cilastatin,levofloxacin,linezolid,and vancomycin were given successively,and multiple debridement and drainage were performed,but the patient remained febrile and had recurrent infection indicators.According to the relevant guidelines and evidence-based evidence,combined with the patient's infection indicators,pathogen results and creatinine clearance rate,the clinical pharmacists recommended stopping vancomycin and changing to cefazolin,and the clinicians adopted it.After that,the patient's inflammatory indicators gradually decreased,and the body temperature stabilized.After 28 days of piperacillin-tazobactam administration,the patient developed a reduction in white blood cell count(2.34×109·L-1)and potassium(2.98 mmol·L-1).The pharmacist recommended prompt discontinuation of the drug,and the patient's white blood cell count and potassium gradually recovered.Eventually,after anti-infective treatment and surgical intervention,the patient was discharged with closure of the infected foci,conversion of multiple blood cultures to negative,and stabilisation of body temperature and renal function.This case reflects the role of clinical pharmacists in the management of drug treatment of critically ill patients,and may provide practical experience and reference for clinical treatment of such cases.

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

OBJECTIVE To explore the potential mechanism of Yiqi Wenyang Recipe in the intervention of allergic rhinitis(AR)mice.METHODS C57/BL6 mice were randomly divided into blank,model,Yiqi Wenyang Recipe and Yiqi Wenyang Recipe+EX-527[Sirtuin 1(SIRT1)inhibitor]groups.The AR model of mice was established by ovalbumin based challenge sensitization method,each group received corresponding intervention measures.Assessment of behavioral changes in mice;nasal mucosal lesions were observed by HE and toluidine blue staining;the serum levels of interleukin-4(IL-4),interferon-γ(IFN-γ),and immunoglobulin E(IgE)were measured by ELISA;the expression levels of phospho-Janus kinase 2(p-JAK2),phospho-signal transducer and activator of transcription 6(p-STAT6),phospho-dynamin-related protein 1(p-Drp1),SIRT1,peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)in nasal mucosa were determined by Western blot combined with immunofluorescence;reactive oxygen species(ROS)levels were detected by fluorescent probe method;the morphological changes of mitochondria in the microstructure of na-sal mucosa were observed by transmission electron microscopy.RESULTS Compared with the blank group,the frequency of scratch-ing and sneezing in the model group was significantly increased,and a large number of eosinophils and mast cells were found in the na-sal mucosa(P<0.05);compared with the model group,the nasal allergic symptoms and the level of nasal mucosal inflammatory reaction in the Yiqi Wenyang Recipe group were significantly improved(P<0.05);compared with the Yiqi Wenyang Recipe group,the scratch-ing and sneezing of mice in the Yiqi Wenyang Recipe+EX-527 group increased again,and the counts of eosinophils and mast cells in nasal mucosa increased significantly(P<0.05).Compared with the model group,the levels of serum IL-4 and IgE in the Yiqi Wenyang Recipe group decreased,while the level of serum IFN-γ increased(P<0.05);the serum IL-4 and IgE of mice in the Yiqi Wenyang Recipe+ex-527 group were significantly higher than those in the Yiqi Wenyang Recipe group(P<0.05).Western blot and immunofluo-rescence showed that Yiqi Wenyang Recipe could effectively inhibit the increase of p-JAK2,p-STAT6,p-Drp1(ser616)levels induced by ovalbumin sensitization,as well as the decrease of SIRT1 and PGC-1 α expression(P<0.01);however,the intervention of EX-527 significantly blunted the regulatory effect of Yiqi Wenyang Recipe on the above signaling molecules(P<0.05,P<0.01).The results of transmission electron microscopy and fluorescent probe showed that in the model group,a large number of spherical mitochondria were found in the mitochondria of nasal mucosa,and the level of ROS was significantly increased(P<0.01);;the intervention of Yiqi We-nyang recipe effectively restored the long tubular morphology of mitochondria and reduced ROS level(P<0.01);,while the intervention of EX-527 weakened the above improvement effect(P<0.01).CONCLUSION Yiqi Wenyang Recipe can regulate SIRT1 to activate PGC-1α,and then inhibit Drp1 mediated excessive mitochondrial fission to intervene AR;SIRT1 may be one of the important targets of Yiqi Wenyang Recipe in the intervention of AR.

Objective:To develop a clinical automated diagnostic system for temporomandibular disor-ders(TMD)based on the diagnostic criteria for TMD(DC/TMD)to assist dentists in making rapid and accurate clinical diagnosis of TMD.Methods:Clinical and imaging data of 354 patients,who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024,were retrospectively collected.The study developed a clinical automated diagnostic system for TMD using the DC/TMD,built on the.NET Framework platform with branching statements as its in-ternal structure.Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored.Diagnostic efficacy of the TMD clinical automated diagnostic system for de-generative joint diseases,disc displacement with reduction,disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evalua-ted and compared with a specialist in the field of TMD.Accuracy,precision,specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist.Results:Diagnoses for various TMD subtypes,including pain-related TMD(arthralgia,myalgia,headache attribu-ted to TMD)and intra-articular TMD(disc displacement with reduction,disc displacement with reduc-tion with intermittent locking,disc displacement without reduction with limited opening,disc displace-ment without reduction without limited opening,degenerative joint disease and subluxation),using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD spe-cialist based on DC/TMD.Both the system and the expert showed low sensitivity for diagnosing degenera-tive joint disease(0.24 and 0.37,respectively),but high specificity(0.96).Both methods achieved high accuracy(＞0.9)for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening.The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system,lower than the expert(0.87),while both had high specificity(0.92).The Kappa values for most TMD subtypes were close to 1,ex-cept the disc displacement without reduction without limited mouth opening,which had a Kappa value of 0.68.Conclusion:This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD.The system is designed to facilitate the rapid and accurate diagnosis and classi-fication of TMD,and is expected to be an important tool in clinical scenarios.

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest(RF),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),and categorical boosting(CatBoost).Methods We obtained the ex-pression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prog-nosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost mod-els were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation.Results A total of 151 differentially expressed protein-coding genes related to survival prog-nosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance.Conclusions Three protein-coding genes(UGP2,C3orf80,and SPC25)were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.