Objective To explore adverse event(AE)signals of sunitinib and to provide a reference for rational drug monitoring based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database.Methods Report odds ratio method(ROR),proportional report ratio method(PRR),polynomial gamma Poisson distribution reduction method(MGPS),and Bayesian confidence interval progressive neural network method(BCPNN)were used to detect the data risk signal strength of sunitinib from the first quarter of 2006 to the third quarter of 2023.Results A total of 35 720 AE reports of sunitinib were retrieved,with 310 positive signals.Most AEs occurred in the first 30 days after treatment(39.71％).Serious AE accounted for 76.37％;27 system organ classifications(SOCs)were involved in positive signals,and the top three were systemic diseases,various reactions at the administration site,gastrointestinal system diseases,and various examinations.High frequency of death,diarrhea,disease progression,and fatigue;65％of the top 20 AEs were new adverse reactions,such as tumor rupture and diffuse proliferation of uveal melanocytes.Conclusion The evaluation of sunitinib should be improved,and medication monitoring should be strengthened to ensure the safety of patients.

Objective To explore adverse event(AE)signals of sunitinib and to provide a reference for rational drug monitoring based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database.Methods Report odds ratio method(ROR),proportional report ratio method(PRR),polynomial gamma Poisson distribution reduction method(MGPS),and Bayesian confidence interval progressive neural network method(BCPNN)were used to detect the data risk signal strength of sunitinib from the first quarter of 2006 to the third quarter of 2023.Results A total of 35 720 AE reports of sunitinib were retrieved,with 310 positive signals.Most AEs occurred in the first 30 days after treatment(39.71％).Serious AE accounted for 76.37％;27 system organ classifications(SOCs)were involved in positive signals,and the top three were systemic diseases,various reactions at the administration site,gastrointestinal system diseases,and various examinations.High frequency of death,diarrhea,disease progression,and fatigue;65％of the top 20 AEs were new adverse reactions,such as tumor rupture and diffuse proliferation of uveal melanocytes.Conclusion The evaluation of sunitinib should be improved,and medication monitoring should be strengthened to ensure the safety of patients.

Objective To explore the value of model established with radiomics features based on contrast enhanced arterial phase CT and model with radiogenomics for predicting prognosis of ovarian serous cystadenocarcinoma(OSC).Methods Enhanced arterial phase CT images of 110 OSC patients were retrospectively collected from 2 centers and The Cancer Imaging Archive(TCIA)database.The radiomics features were extracted,among those related to prognosis were selected to establish a radiomics Cox regression model.Genes data of 399 OSC patients were obtained from The Cancer Genome Atlas(TCGA)database,and genes related to the radiomics features included in the above radiomics model were identified with high Pearson correlation coefficient,and then enrichment gene analyses were performed.For 57 OSC cases with complete enhanced CT and gene data,the hub genes which had the highest connectivity with radiomics prognosis predicting model were detected using Cox regression and protein-protein interaction(PPI).Furthermore,a radiogenomics prognosis predicting model was established with the hub genes.The efficiencies of these 2 models for predicting prognosis of OSC patients were analyzed.Results Finally,the radiomics model included 5 OSC prognosis-related radiomics features,with C-index of 0.782 and 0.735 in corresponding training and test set,respectively.Meanwhile,the radiogenomics model included 30 prognostic hub genes,with C-index of 0.673 and 0.659 in corresponding training and test set,respectively.The survival rates of patients with better predicted prognosis according to radiomics model and radiogenomics model were both higher compared with the others(both P＜0.05).Totally 1 135 mRNA genes were found being associated with radiomics model,including biological behaviors such as cell adhesion,and signaling pathways such as PI3K-Akt,extracellular matrix receptor interaction pathway and type 1 diabetes pathway.Conclusion The radiomics model was effective for predicting prognosis of OSC patients.Analysis of mRNA bioinformatics in OSC patients might provide biological interpretations for the radiomics model.

Purpose This study uses the diffusion tensor imaging to explore diffusion metrics changes of corpus callosum subregion,and to further analyze the relationship among these changes and the cognitive and emotional in adults with primary hypothyroidism.Materials and Methods From October 2019 to September 2021,32 hypothyroidism patients were recruited from Gansu Provincial Hospital,whereas 33 healthy controls were recruited through advertisements.The comprehensive thyroid-related hormone levels tests,as well as neurocognitive/neuropsychiatric assessment and diffusion tensor imaging data of all participants were carried out.The differences in corpus callosum subgroups of diffusion metrics between the two groups were recorded and compared,the partial relationships between these diffusion metrics and thyroid-related hormone levels and neurocognitive/neuropsychiatric function were analyzed and measured.Receiver operating characteristic curves were constructed to evaluate the diagnostic performance.Results Lower fraction anisotropy,higher mean diffusivity and radial diffusivity in genu and body of the corpus callosum and higher axial diffusivity in genu of the corpus callosum were found in hypothyroidism compared with healthy controls(P<0.01).These diffusion metrics were negatively correlated with cognition and emotion(r=-0.448-0.440,P=0.010-0.043),and the fraction anisotropy value in genu of the corpus callosum had the largest area under the curve(0.777).Conclusion Hypothyroidism patients show widespread microstructural changes within the genu and body of the corpus callosum,which,respectively,associated with cognition and emotion.This study provides a new perspective to further understanding the pathophysiology of the cerebral impairment in hypothyroidism.

Objective:To construct a combined radiomics model based on preoperative enhanced computed tomography (CT) examination for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and provide biological explanations for the radiomics model.Methods:The retrospective cohort study was conducted. The messenger RNA (mRNA) of 424 HCC patients, the clinicopathological data of 39 HCC patients entered into the Cancer Genome Atlas database from its establishment until January 2023, and the clinicopathological data of 53 HCC patients who were admitted to the Gansu Provincial People′s Hospital from January 2020 to January 2023 were collected. The 92 HCC patients were randomly divided into a training dataset of 64 cases and a test dataset of 28 cases with a ratio of 7∶3 based on a random number table method. The CT images of patients in the arterial phase and portal venous phase as well as the corresponding clinical data were analyzed. The 3Dslicer software (version 5.0.3) was used to register the CT images in the arterial phase and portal venous phase and delineate the three-dimensional regions of interest. The original images were preprocessed and the corresponding features were extracted by the open-source software FAE (version 0.5.5). After selecting features using the Least Absolute Shrinkage and Selection Operator, the radiomics model was constructed and the radiomics score (R-score) was calculated. The nomogram was constructed by integrating clinical parameters, imaging features and R-score based on Logistic regression. The gene modules related to radiomics model were obtained and subjected to enrichment analysis by conducting weighted gene co-expression network analysis and correlation analysis. Observation indicators: (1) comparison of clinical characteristics of patients with different MVI properties; (2) establishment of MVI risk model; (3) evaluation of MVI risk model; (4) clustering of gene modules; (5) functional enrichment of feature-correlated gene modules. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of count data was conducted using the chi-square test. The intra-/inter-class correlation coefficient (ICC) was used to assess the inter-observer consistency of radiomics feature extracted by different observers. ICC >0.75 indicated a good consistency in feature extraction. The Logistic regression model was used for univariate and multivariate analyses. The receiver operating characteristic curve was drawn, and the area under curve (AUC), the decision curve and the calibration curve were used to evaluate the diagnostic efficacy and clinical practicality of the model. Results:(1) Comparison of clinical characteristics of patients with different MVI properties. Of 92 HCC patients, there were 47 cases with MVI-positive and 45 cases with MVI-negative, and there were significant differences in hepatitis, tumor diameter, peritumoral enhancement, intratumoral arteries, pseudocapsule and smoothness of tumor margin between them ( χ2=5.308, 9.977, 47.370, 32.368, 21.105, 31.711, P<0.05). (2) Establishment of MVI risk model. A total of 1 781 features were extrac-ted from arterial and portal venous phases of the intratumoral and peritumoral regions. After feature dimension reduction, 8 radiomics features were selected from arterial and portal venous phases to construct the combined model. Results of multivariate analysis showed that peritumoral enhancement, intratumoral arteries, pseudocapsule, smoothness of tumor margins, and R-score were independent risk factors for MVI in patients with HCC [ hazard ratio=0.049, 0.017, 0.017, 0.021, 2.539, 95% confidence interval ( CI) as 0.005-0.446, 0.001-0.435, 0.001-0.518, 0.001-0.473, 1.220-5.283, P<0.05]. A nomogram model was constructed incorporating peritumoral enhancement, intratumoral arteries, pseudocapsule, smoothness of tumor margins, and R-score. (3) Evaluation of the MVI risk model. The AUC of radiomics model was 0.923 (95% CI as 0.887-0.944) and 0.918 (95% CI as 0.894-0.945) in the training dataset and test dataset, respectively. The AUC of nomogram model, incorpora-ting both the R-score and radiomics features, was 0.973 (95% CI as 0.954-0.988) and 0.962 (95% CI as 0.942-0.987) in the training dataset and test dataset, respectively. Results of decision curve showed that the nomogram had better clinical utility compared to the R-score. Results of calibration curve showed good consistency between the actual observed outcomes and the nomogram or the R-score. (4) Clustering of gene module. Results of weighted gene co-expression network analysis showed that 8 gene modules were obtained. (5) Functional enrichment of feature-related gene modules. Results of correlation analysis showed 4 gene modules were significantly associated with radiomics features. The radiomics features predicting of MVI may be related to pathways such as the cell cycle, neutrophil extracellular trap formation, and PPAR signaling pathway. Conclusions:The combined radiomics model based on preoperative enhanced CT imaging can predict the MVI status of HCC. By obtaining mRNA gene expression profiles associated with radiomics features, a biological interpretation of the radiomics model is provided.

Objective:To investigate the association of polymorphisms at the matrix metalloproteinase(MMP)-3-1612 position of the promotor region with the inflammatory response and oxidative stress in elderly patients with cerebral ischemic stroke.Methods:In this retrospective study, 129 elderly patients with cerebral infarction diagnosed and treated in our hospital between March 2019 and March 2021 were enrolled as the study group, and 110 healthy subjects were selected as the control group.Polymorphisms of the MMP-3-1612 position in the promotor region, the inflammatory response and oxidative stress were examined using appropriate parameters and the associations between them were analyzed. Results:Compared with the control group, the proportions of patients with hypertension, diabetes, and smoking history in the study group were significantly higher( χ2=16.05, 17.19, 14.19, all P<0.05), and the levels of fasting blood glucose, low-density lipoprotein, and homocysteine were also significantly higher( t=6.22, 3.64, 2.69, all P<0.05).Meanwhile, compared with patients carrying the MMP-3-5A/6A or the MMP-3-6A/6A genotype, the levels of serum inflammatory markers such as high mobility group box-1 protein(HMGB1), fractalkine(FKN), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and interleukin-17(IL-17)in patients carrying the MMP-3 gene 5A/5A genotype were significantly higher(all P<0.05).In addition, the expression of serum oxidative stress-related molecules Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid-2 related factor2(Nrf2), antioxidant response element(ARE), quinone oxidoreductase 1(NQO1), and heme oxygenase-1(HO-1)was also significantly increased(all P<0.05), but there was no difference in these markers between patients carrying the MMP-3-5A/6A genotype and patients carrying the MMP-3-6A/6A genotype( P>0.05).Patients carrying the 5A/5A genotype and the 6A/6A genotype exhibited only one 97 bp band and one 120 bp band, respectively, while the patients carrying the 5A/6A genotype exhibited two 97 bp bands and two 120 bp bands.There was no statistical difference in the number of patients carrying the 5A/6A genotype in the cerebral infarction group compared with the control group( P>0.05), and the number of patients carrying the 5A/5A genotype in the cerebral infarction group was higher than that in the control group(69% or 53.49% vs.35% or 31.82%, χ2=11.34, P<0.05).Polymorphisms of the MMP-3 gene had a positive correlation with the risk of stroke( r=0.25, P<0.05). MMP-3-1612 gene polymorphism( OR=7.21, 95% CI: 1.13-1.83, P=0.01), elevated blood glucose( OR=1.27, 95% CI: 1.18-2.06, P<0.001), high homocysteine( OR=1.05, 95% CI: 1.08-1.58, P<0.01), hypertension( OR=5.414, 95% CI: 1.140-4.46, P<0.01), elevated low-density lipoprotein( OR=4.03, 95% CI: 1.03-2.35, P=0.02), coronary heart disease( OR=1.17, 95% CI: 1.47-3.19, P<0.01)and diabetes( OR=8.52, 95% CI: 1.32-4.71, P<0.01)were risk factors for cerebral infarction. Conclusions:In elderly patients with cerebral infarction, polymorphisms of the MMP-3-1612 position in the promotor region is closely related to the risk of cerebral ischemic stroke, the inflammatory response and oxidative stress.MMP-3 gene polymorphisms are risk factors for stroke.

Objective:To investigate the abnormal patterns of spontaneous neural activity of patients with type 2 diabetes comorbid depression (T2DD) by using resting-state functional magnetic resonance imaging (rs-fMRI) fractional amplitude of low-frequency (fALFF) analysis, and determine the neuroimaging features of brain damage in T2DD patients.Methods:A perspective study was performed. Fifty-nine type 2 diabetes mellitus (T2DM) patients and 52 T2DD patients, admitted to and accepted treatment in Department of Endocrinology of our hospital from November 2017 to November 2020, were chosen; another 57 healthy controls matched with gender, age and education level, admitted to our hospital at the same time period were enrolled. Their clinical data, neuropsychological test and rs-fMRI data were collected; whole brain fALFF values were calculated, and fALFF values of different brain regions were compared in subjects of the 3 groups. Pearson correlation analysis was used to verify the correlations of fALFF values with clinical variables and neuropsychological scale scores.Results:The fALFF values in bilateral precuneus showed significant difference among the three groups ( P<0.05). The fALFF values in bilateral precuneus of the T2DD and T2DM groups were significantly lower than those in heathy control group ( P<0.05), and those in the T2DD group were lower than those in the T2DM group without significant difference ( P>0.05). Pearson correlation analysis showed that there were no correlations of fALFF values with clinical data and psychometric scale scores in T2DD group and T2DM group ( P>0.05). Conclusion:The abnormal patterns of spontaneous brain activity in the bilateral precuneus may be the neuroimaging markers of brain damage in T2DD patients.

Type 2 diabetes often comorbid with depression (T2DD),leading to poor compliance,poor self-management and increasing social burden.However,the underlying pathophysiological mechanism has not been fully elucidated.Numerous studies mainly focused on the hypothalamic-pituitary-adrenalaxis,immune inflammatory system,insulin resistance and neuroimaging changes of T2DD.Thus the present review will summarize the major recent advances in current understanding of T2DD.

Type 2 diabetes often comorbid with depression (T2DD),leading to poor compliance,poor self-management and increasing social burden.However,the underlying pathophysiological mechanism has not been fully elucidated.Numerous studies mainly focused on the hypothalamic-pituitary-adrenalaxis,immune inflammatory system,insulin resistance and neuroimaging changes of T2DD.Thus the present review will summarize the major recent advances in current understanding of T2DD.

Objective: To investigate the alterations of the cerebral resting-state spontaneous neural activity in colorectal cancer patients with depressive symptoms. Methods: Thirty-three colorectal cancer patients (patient group) with depression and 43 healthy subjects (control group) underwent the resting state functional magnetic resonance imaging (rs-fMRI). The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. Two independent samples t test were used to compare the ALFF and fALFF values between two groups by DPABI software, and then correlation analysis was performed between ALFF and fALFF with statistical significance and Patient Health Questionnaire (PHQ-9) scores and Generalized Anxiety Disorder (GAD-7) scores. Results: Compared with the control group, the patient group showed significantly lower ALFF and fALFF values in the bilateral precuneus, calcarine gyrus, lingual gyrus, left cuneus, superior, middle, inferior occipital gyrus and right fusiform gyrus (t=-5.730, P<0.05; t=-4.872, P<0.05). There were no significant correlations between the ALFF and fALFF values in these regions and PHQ-9 or GAD-7 scores (P>0.05). Conclusion Spontaneous decrease of neural activity in occipital and parietal lobes exists in colorectal cancer patients with depression at resting-sate, which may be a potential neurobiological marker.