Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

In order to investigate the mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)on liver bile acid(BAs)and lipid metabolism of dairy cows with fatty liver,A liver lip-id accumulation model was established by isolating primary calf hepatocytes and treating them with high concentration of non-esterified fatty acids(NEFA)in vitro.Then,HMGCR overex-pressed adenovirus(Ad-HMGCR)and overexpressed adenovirus control(Ad-GFP)were added.Hepatocyte triglyceride(TAG)was detected by the kit,lipid droplet changes were detected by lip-id droplet fluorescence,and BAs synthesis,fatty acid synthesis and oxidation factor changes were detected by real-time fluorescence quantitative PCR.The results showed that TAG content and lip-id droplet fluorescence were significantly reduced in Ad-HMGCR+NEFA group compared with Ad-GFP+NEFA group.Real-time fluorescence quantitative PCR results showed that CYP7A1,CYP8B1,CYP7B1 and CYP27A1 of hepatocyte BAs synthesis factors in Ad-HMGCR+NEFA group,BAs transporters ABCC2 and ABCB11 and fatty acid synthesis factors ACC1,FAS and SREBP1C were significantly lower than those in Ad-GFP+NEFA group.The levels of BAs syn-thesis factor FXR and lipid oxidation factor CPT1A in Ad-HMGCR+NEFA group were higher than those in Ad-GFP+NEFA group.The results showed that overexpression of HMGCR could significantly reduce BAs and lipid accumulation in the liver of dairy cows with fatty liver.

Objective:To explore the correlation between ultrasonic SWE, blood flow quantitative parameters and the expression levels of MYB-associated protein B (MYBL2) and metastasis-associated 1 (MTA1) in breast cancer tissue.Methods:92 patients with breast cancer diagnosed and treated in our hospital from Jan. 2022 to Dec. 2023 were selected as the study objects, all of whom underwent ultrasonic SWE and blood flow imaging examination. Furthermore, the expression levels of MYBL2 and MTA1 in cancer tissues were detected, and the correlation between ultrasonic SWE and blood flow quantitative parameters and the expression levels of MYBL2 and MTA1 was analyzed.Results:The difference between maximum elastic modulus (Emax) and mean elastic modulus (E mean) in breast cancer patients with different lesion diameters and clinical stages was statistically significant (lesion diameters: t=4.561, 7.347; Clinical stage: t=4.218, 7.554, P<0.001) ; There were statistically significant differences in maximum blood flow velocity (V max), resistance index (RI), pulse index (PI) among breast cancer patients with different clinical stages, differentiation degrees and lymph node metastasis (clinical stage: t=7.055, 3.774, 3.877; Differentiation degree: F=26.830, 21.052, 20.412; Lymph node metastasis: t=7.425, 3.685, 4.956, P<0.001). There were statistically significant differences in E max, E mean, V max, RI and PI among breast cancer patients with different expression levels of MYBL2 and MTA1 (MYBL2: t=4.042, 10.672, 7.471, 6.137, 5.777; MTA1: t=5.968, 10.470, 8.098, 10.238, 7.565, P<0.001). By Spearman correlation analysis, E max and E mean were positively correlated with lesion diameter, clinical stage, MYBL2 expression level and MTA1 expression level ( P<0.001) ; V max, RI and PI were positively correlated with clinical stage, lymph node metastasis, MYBL2 expression level and MTA1 expression level, and negatively correlated with differentiation degree ( P<0.001) . Conclusion:The expression levels of MYBL2 and MTA1 in breast cancer tissue are correlated with the ultrasonic shear wave elastography and blood flow quantitative parameters, which can be used as an important reference index for clinical diagnosis and treatment of breast cancer.

Objective:To explore the correlation between ultrasonic SWE, blood flow quantitative parameters and the expression levels of MYB-associated protein B (MYBL2) and metastasis-associated 1 (MTA1) in breast cancer tissue.Methods:92 patients with breast cancer diagnosed and treated in our hospital from Jan. 2022 to Dec. 2023 were selected as the study objects, all of whom underwent ultrasonic SWE and blood flow imaging examination. Furthermore, the expression levels of MYBL2 and MTA1 in cancer tissues were detected, and the correlation between ultrasonic SWE and blood flow quantitative parameters and the expression levels of MYBL2 and MTA1 was analyzed.Results:The difference between maximum elastic modulus (Emax) and mean elastic modulus (E mean) in breast cancer patients with different lesion diameters and clinical stages was statistically significant (lesion diameters: t=4.561, 7.347; Clinical stage: t=4.218, 7.554, P<0.001) ; There were statistically significant differences in maximum blood flow velocity (V max), resistance index (RI), pulse index (PI) among breast cancer patients with different clinical stages, differentiation degrees and lymph node metastasis (clinical stage: t=7.055, 3.774, 3.877; Differentiation degree: F=26.830, 21.052, 20.412; Lymph node metastasis: t=7.425, 3.685, 4.956, P<0.001). There were statistically significant differences in E max, E mean, V max, RI and PI among breast cancer patients with different expression levels of MYBL2 and MTA1 (MYBL2: t=4.042, 10.672, 7.471, 6.137, 5.777; MTA1: t=5.968, 10.470, 8.098, 10.238, 7.565, P<0.001). By Spearman correlation analysis, E max and E mean were positively correlated with lesion diameter, clinical stage, MYBL2 expression level and MTA1 expression level ( P<0.001) ; V max, RI and PI were positively correlated with clinical stage, lymph node metastasis, MYBL2 expression level and MTA1 expression level, and negatively correlated with differentiation degree ( P<0.001) . Conclusion:The expression levels of MYBL2 and MTA1 in breast cancer tissue are correlated with the ultrasonic shear wave elastography and blood flow quantitative parameters, which can be used as an important reference index for clinical diagnosis and treatment of breast cancer.

Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P＜0.05),and the number of falls was significantly increased(P＜0.001).The expression level of TH protein in brain tissue was significantly decreased(P＜0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P＜0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P＜0.05,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P＜0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P＜0.05,P＜0.001),the falling latency was significantly prolonged(P＜0.05,P＜0.01),the times of falls was significantly reduced(P＜0.001),the expression level of TH protein in brain tissue was significantly increased(P＜0.01,P＜0.001),and the level of serum TNF-α was significantly decreased(P＜0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P＜0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P＜0.01,P＜0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P＜0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.