OBJECTIVE To develop and validate interpretable machine learning models for predicting the risk of medication-related osteonecrosis of the jaw （MRONJ） and surgical outcomes， thereby providing quantitative support for MRONJ risk assessment and treatment decision-making.METHODS Two study cohorts were established. Cohort A adopted a nested case-control study design to develop a predictive model for the risk of MRONJ onset. Cohort B comprised patients with MRONJ from Cohort A who underwent surgical treatment and met the follow-up eligibility criteria， and employed a prospective follow-up cohort study design to develop a predictive model for the efficacy of MRONJ surgery. After missing-data processing， variable standardization， and encoding， predictive features were selected using the least absolute shrinkage and selection operator （LASSO） regression， and collinearity was assessed using the variance inflation factor （VIF）. Random Forest （RF）， eXtreme Gradient Boosting （XGB）， Multi-layer Perceptron （MLP）， Support Vector Machine （SVM）， and Gaussian Naive Bayes （NB） models were subsequently developed using the selected features. Hyperparameter optimization and internal performance evaluation were performed using two-level nested cross-validation repeated 20 times. In Cohort B， the synthetic minority over-sampling technique （SMOTE） was applied within the inner training folds to address class imbalance. Model performance was comprehensively evaluated using the receiver operating characteristic （ROC） curve， the precision-recall （PR） curve， calibration curve， and decision curve analysis （DCA）. Shapley additive explanations （SHAP） were used to quantify the relative contributions of individual clinical features to model predictions.RESULTS Seven clinical features， including alkaline phosphatase and tooth extraction， were retained for Cohort A； whereas eight clinical features， including age and duration of medication use， were retained for Cohort B. In Cohort A， the area under the ROC curve， the area under the PR curve， Brier score， sensitivity， and specificity of the RF model were 0.94， 0.92， 0.09， 0.92， and 0.85， respectively； the corresponding values in Cohort B were 0.93， 0.93， 0.12， 0.83， and 0.93， respectively. The results of calibration curves and DCA indicated that the RF models achieved favorable calibration and clinical net benefit， with VIF values for all variables below 5. SHAP visualization results showed that alkaline phosphatase， tooth extraction， and cumulative drug dose made substantial contributions to MRONJ risk prediction in Cohort A， whereas age， duration of medication use， and MRONJ stage contributed substantially to surgical outcome prediction in Cohort B.CONCLUSIONS The RF-based models for predicting MRONJ risk and surgical outcomes demonstrated good discrimination， accuracy of probabilistic predictions， and potential clinical utility during internal validation. These models may provide decision support for comprehensive MRONJ risk management and individualized clinical decision-making. However， external validation in independent， multicenter， and geographically diverse cohorts is still required.

Objective To investigate the changes and diagnostic value of serum hypoxia inducible factor 1 subunit alpha(HIF-1α)and Toll-like receptor 4(TLR4)levels in patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary Aspergillosis infection.Methods A total of 240 COPD patients who visited Xi'an Qinhuang Hospital(hereinafter referred to as the hospital)from December 2020 to Decem-ber 2023 were selected as the study subjects in the study,and another 218 volunteers who underwent physical examinations at the hospital were selected as the control group.The COPD patients were separated into an in-fected group(124 cases)and an uninfected group(116 cases)based on whether they had pulmonary Aspergil-losis infection.Enzyme-linked immunosorbent assay was applied to detect the levels of HIF-1α and TLR4 in patients.Fully automated biochemical analyzer was applied to detect lactate dehydrogenase(LDH)and albu-min(ALB)levels.Multivariate Logistic regression was applied to analyze the influencing factors of infection in COPD patients.Pearson correlation was applied to analyze the correlation between HIF-1α and TLR4 levels in the infected group.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic val-ue of HIF-1α and TLR4 levels for the occurrence of infection in COPD patients.Results Compared with the control group,the COPD group showed an increase in HIF-1α and TLR4 levels(P＜0.05).Compared with the uninfected group,the proportion of dyspnea,antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,mechanical ventilation procedures,the longer glucocorticosteroid(GC)use time,and levels of LDH,HIF-1α,TLR4 in the infected group were higher(P＜0.05),while the level of ALB was lower(P＜0.05).The types of antibiotics＞3 types,the duration of antibiotic use ≥ 14 days,the duration of GC use,and elevat-ed levels of LDH,HIF-1α,and TLR4 were independent risk factors for infection in COPD patients(P＜0.05),while elevated level of ALB was an independent protective factor for infection in COPD patients(P＜0.05).The levels of HIF-1α and TLR4 in the infected group were positively correlated(r=0.453,P＜0.001).The area under the curve(AUC)of HIF-1α and TLR4 in diagnosing infection in COPD patients alone was 0.816 and 0.813,and the AUC of their combined diagnosis was 0.930,which was better than their indi-vidual diagnoses(Zcombination-HIF-1α=4.923,Z combination-TLR4=5.192,P＜0.001,P＜0.001).Conclusion The levels of HIF-1α and TLR4 increase in COPD patients,and further increase after infection with pulmonary Aspergil-lus.They are independent risk factors for infection in patients,and the two are positively correlated.The combined di-agnosis of pulmonary aspergillosis has certain value and provides a theoretical basis for clinical diagnosis.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

Objective:To observe family meetings in hospice care centers of tertiary hospitals and to clarify the experience and methods of patient-centered communication.Methods:From Agust 2020 to January 2021, the field research was conducted in the hospice wards of Beijing Haidian Hospital for 6 months. Audio, video, and verbatim transcripts were collected from palliative care family meetings by purposive sampling method. Family meeting transcripts were analyzed by a content analysis approach.Results:A total of 25 family meeting recordings and transcripts and 21 case observation data were collected. There were 10 males and 15 females, aged 39-90 years old. Three themes and nine sub-themes were identified to summarize family meetings: patient-centered foundational support and key measures -- preparation for family meeting (environmental preparation, information preparation); patient centered communication implementation path--how the family meeting was conducted (structured communication, professional communication, patient-centered communication); patient-centered communication effectiveness--outcomes after the family meeting (directly facing the current situation, clarifying choices, reducing regrets, feeling humanistic). A family meeting instruction manual had been developed.Conclusions:The patient-centered family meeting for terminal patients is an important platform for tertiary hospitals to achieve systematic communication among medical workers, patients, and their families. Through the family meeting, medical workers, patients, and their families can share information, with patients and their families feeling supported by a multidisciplinary team and humanistic care. The family meeting guidebook is anticipated to enhance the organizational and communication skills of healthcare professionals in facilitating family meetings.

Objective To investigate the improving effect and mechanism of the traditional Chinese herbal medicine Glabridin(GLA)on cognitive impairment in Parkinson's disease(PD)mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),and its protective effect on the cerebral cortex and hippocampus through affecting the extracellular regulated protein kinases(ERK)signaling pathway involved in the regulation of neural plasticity.Methods A total of 120 C57BL//6N mice were randomly divided into control group,model group,GLA control group and MPTP+GLA low,medium and high-dose groups,with 20 mice in each group.The mouse PD model was established by intraperitoneal injection of MPTP 20 mg/kg,and the control group was injected with the same dose of normal saline.The GLA control group was given 50 mg/kg GLA by gavage;the MPTP+GLA low,medium and high dose groups were given 20,30 and 50 mg/kg GLA by gavage 1 hour after each MPTP administration,once a day for 7 consecutive days.The learning and memory abilities of the mice in each group and the pathological changes of hippocampal tissue were observed,as well as the changes in the contents of tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),malondialdehyde(MDA),superoxide dismutase(SOD),tyrosine hydroxylase(TH)and protein expression levels of phosphorylated-ERK 1/2(p-ERK1/2)in the cerebral cortex.Results Compared with the control group,the levels of MDA and TNF-α,IL-18 in the cerebral cortex of the model group were significantly increased[MDA(nmol/mg):4.68±0.51 vs.2.05±0.22,TNF-α(μg/L):116.87±15.65 vs.48.52±7.83,IL-18(μg/L):57.52±6.89 vs.24.26±1.89,all P<0.05],while the activity of SOD was significantly decreased(U/mg:77.84±7.84 vs.130.89±18.56,P<0.05).Compared with the model group,the contents of TNF-α,IL-18,and MDA in each MPTP+GLA group were significantly decreased,while the activity of SOD was significantly increased(all P<0.05),and the change in the high-dose MPTP+GLA group was more obvious.The learning and memory ability of the high-dose MPTP+GLA group was significantly improved,the number of neurons in the hippocampus tissue decreased,the neurodegeneration was improved,and the glial cell proliferation was reduced.The results of immunohistochemistry showed that compared with the model group,the loss of TH positive cells in the high-dose MPTP+GLA group was significantly reduced[absorbance(A value):cerebral cortex was 39.14±3.25 vs.23.14±3.1,hippocampus was 72.14±4.25 vs.52.16±3.32,both P<0.05],and the expression of p-ERK1/2 positive cells was significantly inhibited(A value:cerebral cortex was 63.91±3.55 vs.88.35±6.41,hippocampus was 73.36±3.52 vs.93.25±6.73,both P<0.05).Western blotting showed that compared with the model group,the protein expression level of cerebral cortex and hippocampus TH in the high-dose MPTP+GLA group was significantly increased(gray value:cerebral cortex was 0.71±0.09 vs.0.53±0.06,hippocampus was 0.68±0.06 vs.0.45±0.03,both P<0.05),and the protein expression level of p-ERK1/2 was significantly inhibited(gray value:cerebral cortex was 0.76±0.10 vs.0.96±0.08,hippocampus was 0.74±0.06 vs.0.96±0.12,both P<0.05).Conclusions The traditional Chinese medicine GLA can improve the learning and memory ability of MPTP-induced PD mice,as well as prevent and treat MPTP-induced neuronal damage and glial cell proliferation.The ERK signaling pathway is associated with neural damage in PD brain tissue.GLA protects the learning and memory ability of MPTP-induced PD mice by inhibiting the ERK signaling pathway.

Objective To evaluate iron deposition in gray matter nuclei in patients with cerebral small vessel disease(CSVD)based on quantitative susceptibility mapping(QSM)and to analyze its correlation with cognitive function.Methods Patients with CSVD attending the outpatient clinic in the Department of Neurology at Xuanwu Hospital of Capital Medical University from December 2016 to November 2022,and healthy controls recruited from previous studies in the Department of Radiology and Nuclear Medicine at Xuanwu Hospital of Capital Medical University from September 2022 to November 2022 were retrospectively consecutively collected.Baseline data of CSVD patients and healthy controls was collected and compared,including age,sex,past history(hypertension,diabetes,hyperlipidemia),smoking history,alcohol consumption history and Montreal cognitive assessment(MoCA)scale score.MRI of all CSVD patients and healthy controls were collected,including three-dimensional T1 weighted imaging,QSM,T2 weighted imaging,and fluid attenuated inversion recovery(FLAIR)sequence imaging.According to the MRI-related imaging features and CSVD total burden score,the patients were divided into mild CSVD(CSVD-m)group and severe CSVD(CSVD-s)group,and healthy controls were the control group.QSM was used to obtain the susceptibility values of gray matter nuclei for all CSVD patients and controls.One-way covariance analysis and Bonferroni correction were used to compare the gray matter nuclei susceptibility values among the three groups.Spearman correlation analysis was performed between susceptibility values of gray matter nuclei with statistically significant differences in susceptibility values and cognitive function.Results A total of 61 cases of CSVD patients were included,including 29 cases in the CSVD-s group and 32 cases in the CSVD-m group;32 healthy controls were included in the control group.(1)There was no statistically significant difference in age,sex,hypertension,diabetes,hyperlipidemia,smoking,and alcohol consumption between the CSVD-s group,CSVD-m group and control group(all P＞0.05).The MoCA scale scores of the CSVD-s group and CSVD-m group were lower than those of the control group(25.0[22.5,27.5]points,27.0[25.0,29.0]points than 28.0[27.0,29.0]points,H=15.006,P＜0.01).The difference in the imaging features distribution of cerebral microbleeds,white matter hyperintensity,and perivascular space among the CSVD-s group and the CSVD-m group was statistically significant(all P＜0.05).(2)The differences in susceptibility values of the left putamen(F=4.790),pallidus(F=12.896),hippocampus(F=3.904)and the right putamen(F=36.278),pallidus(F=39.449),caudate nucleus(F=6.797),and thalamus(F=6.525)were statistically significant among the three groups(all P＜0.05).After Bonferroni correction,the susceptibility values of the left putamen and pallidus and the right putamen,pallidus,caudate nucleus,and thalamus in the CSVD-s group were higher than those of the control group(all P＜0.05);the susceptibility values of the left pallidus and the right pallidus,putamen,and thalamus in the CSVD-m group were higher than those of the control group(all P＜0.01),and the left hippocampus was lower than that of the control group(P=0.045).(3)The susceptibility values of the bilateral putamen were significantly negatively correlated with MoCA scale score(left putamen:rs=-0.316,P=0.015;right putamen:rs=-0.316,P=0.014).Conclusion Abnormal iron metabolism occurs in gray matter nuclei of CSVD patients,and iron deposition in the putamen correlate with cognitive dysfunction.

Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.