AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

Objective:To explore the interaction effects on brain activity between the smoking addiction and weight status by resting-state functional magnetic resonance imaging.Methods:Retrospective analysis of clinical data and resting-state functional magnetic resonance imaging data were analyzed from 99 recruited subjects from January 2019 to December 2021. All participants were divided into four groups: overweight smokers ( n=24), normal-weight smokers ( n=28), overweight non-smokers ( n=19), and normal weight non-smokers ( n=28). Calculate regional homogeneity (ReHo) to reflect the internal brain activity of the subjects. Two-way ANOVA was used to detect the interaction effects between smoking addiction and overweight on ReHo by SPM12 software, correcting for age, years of education and head motion. Results:The interaction effect between smoking addiction and overweight on ReHo was significant in right superior frontal gyrus(x, y, z=15, 9, 60)(GRF corrected, Pvoxel<0.005, Pcluster<0.05). The ReHo value in the right superior frontal gyrus of overweight smokers was significantly higher than that of normal weight smokers ( t=3.768, P<0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight non-smokers were significantly lower than those of normal weight non-smokers ( t=-3.242, P=0.002, Bonferroni corrected). The ReHo values in the right superior frontal gyurs of normal-weight smokers were significantly lower than those of normal weight non-smokers( t=-3.540, P=0.001, Bonferroni corrected). The ReHo values in the right superior frontal gyrus of overweight smokers were significantly higher than those of overweight non-smokers ( t=3.392, P=0.002, Bonferroni corrected). Correlation analyses showed that the strengthen ReHo value in right superior frontal gyrus was positively associated with pack-year in smoking addicts( r=0.387, P=0.007, Bonferroni corrected). Conclusion:Smoking addiction and overweight have an antagonistic effect on brain activity in the right superior frontal gyrus, which may provide potential therapeutic targets for individuals with comorbidity of smoking addiction and overweight.

Objective:To investigate the correlation between brain gray matter volume (GMV) and interactive effects of smoking addiction and overweight.Methods:We retrospectively analyzed the clinical data and resting-state functional magnetic resonance imaging data of 99 subjects recruited from January 2019 to December 2021 through online platforms such as WeChat, including the following four groups: overweight smoking addiction group ( n=24), normal-weight smoking addiction group ( n=28), overweight non-smoking group ( n=19), and normal-weight non-smoking group ( n=28). All subjects underwent 3.0T MRI. We used voxel-based morphometry (VBM) to compare gray matter volume (GMV) among the four groups. A two-way analysis of variance was conducted with age, years of education, and head motion as covariates to explore the interaction effects between smoking addiction and weight status on GMV, the main effect of smoking addiction and main effect of overweight, which were then correlated with clinical data. Results:Significant interactive effects of smoking addiction and overweight were observed in the left dorsolateral prefrontal cortex (DLPFC) (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Correlation analysis showed a quadratic effect between body mass index and left DLPFC GMV (β=-3.846, t=-2.134, P=0.036). Additionally, the main effect of smoking addiction was primarily manifested in the bilateral orbitofrontal cortex (OFC)(GRF corrected, P voxel<0.001, P cluster<0.05). Left OFC GMV was negatively associated with the FTND (Fagerstrom Test of Nicotine Dependence) scores ( r=-0.391, P=0.006). And right OFC GMV was negatively correlated with the smoking index ( r=-0.335, P=0.019). No statistically significant main effect of overweight was found at the aforementioned threshold. Conclusion:Smoking addiction and overweight have antagonistic effects on left DLPFC GMV.

Objective:This study aims to investigate the dynamic patterns of intrinsic neural activity and their relationships with Internet Addiction Test (IAT) scores in individuals with internet gaming disorder (IGD).Methods:Resting state functional magnetic resonance imaging (fMRI) scanning was performed on 33 individuals with IGD (IGD group) who were admitted to the psychiatric department of First Affiliated Hospital of Zhengzhou University and 40 healthy volunteers (control group) recruited through the online platform. The dynamic regional homogeneity (dReHo) values were calculated. The two-sample t test was used to analyze the differences of dReHo values between two groups (Gaussian random field corrected, voxel level P<0.001, cluster level P<0.05). Spearman correlation analyses were used to analyze the correlations between IAT scores and dReHo values of brain regions with statistically significant differences between IGD group and control group. Results:Compared with the control group, the IGD group showed increased dReHo values in the right thalamus, right caudate nucleus, left putamen, bilateral medial superior frontal gyrus, bilateral supplementary motor area, and bilateral superior frontal gyrus ( t=3.84-4.94, Gaussian random field corrected, voxel level P<0.001, cluster level P<0.05). The dReHo value in the right medial superior frontal gyrus was positively correlated with IAT scores ( r=0.395, P=0.023) in IGD group. Conclusion:Individuals with IGD exhibited a wide range of abnormal dynamic patterns of intrinsic neural activity in pivotal regions associated with reward processing and cognitive control functions (the fronto-striato-thalamic circuit), providing new insights into the underlying neural mechanisms of IGD.

Objective:To investigate the correlation between brain gray matter volume (GMV) and interactive effects of smoking addiction and overweight.Methods:We retrospectively analyzed the clinical data and resting-state functional magnetic resonance imaging data of 99 subjects recruited from January 2019 to December 2021 through online platforms such as WeChat, including the following four groups: overweight smoking addiction group ( n=24), normal-weight smoking addiction group ( n=28), overweight non-smoking group ( n=19), and normal-weight non-smoking group ( n=28). All subjects underwent 3.0T MRI. We used voxel-based morphometry (VBM) to compare gray matter volume (GMV) among the four groups. A two-way analysis of variance was conducted with age, years of education, and head motion as covariates to explore the interaction effects between smoking addiction and weight status on GMV, the main effect of smoking addiction and main effect of overweight, which were then correlated with clinical data. Results:Significant interactive effects of smoking addiction and overweight were observed in the left dorsolateral prefrontal cortex (DLPFC) (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Correlation analysis showed a quadratic effect between body mass index and left DLPFC GMV (β=-3.846, t=-2.134, P=0.036). Additionally, the main effect of smoking addiction was primarily manifested in the bilateral orbitofrontal cortex (OFC)(GRF corrected, P voxel<0.001, P cluster<0.05). Left OFC GMV was negatively associated with the FTND (Fagerstrom Test of Nicotine Dependence) scores ( r=-0.391, P=0.006). And right OFC GMV was negatively correlated with the smoking index ( r=-0.335, P=0.019). No statistically significant main effect of overweight was found at the aforementioned threshold. Conclusion:Smoking addiction and overweight have antagonistic effects on left DLPFC GMV.

Objective:This study aims to investigate the dynamic patterns of intrinsic neural activity and their relationships with Internet Addiction Test (IAT) scores in individuals with internet gaming disorder (IGD).Methods:Resting state functional magnetic resonance imaging (fMRI) scanning was performed on 33 individuals with IGD (IGD group) who were admitted to the psychiatric department of First Affiliated Hospital of Zhengzhou University and 40 healthy volunteers (control group) recruited through the online platform. The dynamic regional homogeneity (dReHo) values were calculated. The two-sample t test was used to analyze the differences of dReHo values between two groups (Gaussian random field corrected, voxel level P<0.001, cluster level P<0.05). Spearman correlation analyses were used to analyze the correlations between IAT scores and dReHo values of brain regions with statistically significant differences between IGD group and control group. Results:Compared with the control group, the IGD group showed increased dReHo values in the right thalamus, right caudate nucleus, left putamen, bilateral medial superior frontal gyrus, bilateral supplementary motor area, and bilateral superior frontal gyrus ( t=3.84-4.94, Gaussian random field corrected, voxel level P<0.001, cluster level P<0.05). The dReHo value in the right medial superior frontal gyrus was positively correlated with IAT scores ( r=0.395, P=0.023) in IGD group. Conclusion:Individuals with IGD exhibited a wide range of abnormal dynamic patterns of intrinsic neural activity in pivotal regions associated with reward processing and cognitive control functions (the fronto-striato-thalamic circuit), providing new insights into the underlying neural mechanisms of IGD.

Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.

Animals ; Coronary Vessels ; Diabetes Mellitus ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Rats

Objective:To produce 161Tb from enriched 160Gd 2O 3 isotope-enriched target material and realize domestic production of the novel medical isotope 161Tb. Methods:The 160Gd 2O 3 isotope-enriched target material was irradiated with neutrons by the China Mianyang Research Reactor (CMRR). The no-carrier-added 161Tb product was obtained after the processes of target broken, sample dissolution, separation and purification with lanthanide (LN) resin and solution replacement with diglycolamide (DGA) column. Various key indicators such as γ spectral purity, metal impurity content, specific activity, radiochemical purity, and radioactive concentration were used to conduct the quality inspection and the control of 161Tb products. Results:161TbCl 3 of 33.4 GBq was obtained in a single time with the radioactive concentration of 16.8 GBq/ml, nuclear purity more than 99.9%, and radiochemical purity of 99.2%. Metal impurity content was met the established standards, with the specific activity of 6.02×10 17 Bq/mol. The radiochemical purities of 161Tb labeling with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) after 0 and 72 h were 100% and 95.8% respectively. Conclusion:The preparation of no-carrier-added 161Tb by using LN resin has the advantages of high separation performance and high sample loading, which has great significance in the field of medical isotope preparation and lays a good nuclide guarantee for the research and development of domestic 161Tb-labeled drugs.