BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective To observe the clinical application value of total free-breathing cardiac MR(CMR)examination preliminarily.Methods Two patients who underwent CMR scanning under free-breathing state,including cine,motion correction T1 and T2 mapping,blood flow imaging,and late gadolinium enhancement scanning were retrospectively enrolled,and the qualities of the above images were evaluated and compared with that of conventional CMR images under breath-holding state.Results No significant difference of imaging quality was found between total free-breathing and conventional breath-holding CMR.The differences of left ventricular ejection fraction,cardiac output,left ventricular end-diastolic volume index and left ventricular mass measured based on CMR images under different breath conditions were limited.Conclusion Total free-breathing CMR was feasible in clinical practice,which could provide"one-stop"evaluation of cardiac structure,function and myocardial histological characteristics,hence having promising clinical prospects.

Objective　 To understand the survival status and influencing factors of HIV/AIDS patients who developed low-level viremia (LLV) after receiving antiretroviral therapy in Guizhou Province from 2016 to 2022. Methods　Historical records of HIV/AIDS patients in Guizhou Province were downloaded from the China AIDS Comprehensive Prevention and Treatment Information System. The retrospective cohort method was used to calculate the survival rate usingthe life table method, and the Kaplan-Meier method was used to draw the survival curve. The Cox proportional risk regression model was used to analyze the factors affecting survival time. Results　A total of 12 240 patients with LLV were included, among which 854 had died. The observation time range of cases was 0.5-6.92 years, with the M (P25, P75) years of 3.75 (2.42, 5.00) years. The cumulative survival rates at 1, 2, 3, and 6 years after receiving antiviral treatment were 99.11%, 97.00%, 94.36%, and 85.27%, respectively. The multivariate Cox proportional risk model analysis showed the risk factors for mortality among LLV patients included being male, unmarried (aHR:1.640，95%CI:1.243-2.163), divorced or widowed and unknown (aHR:1.193, 95%CI:1.031-1.381), being of the Buyi ethnicity (aHR:1.625, 95%CI:1.310-2.015), illiteracy, heterosexual transmission, baseline WHO clinical stage Ⅳ (aHR:1.596, 95%CI:1.322-1.927), baseline CD4+T lymphocytes <200 cells/μL, initial treatment regimen being a second-line treatment regimen (aHR:1.835, 95%CI:1.208-2.786), age ≥40 years (aHR:1.498, 95%CI:1.035-2.168) and ≥50 years (aHR:3.514, 95%CI:2.468-5.003) at the beginning of ART, time from diagnosis to treatment ≥1 year (aHR:1.310, 95%CI:1.009-1.702) years, absence of compound sulfamethoxazole usage history, high-level LLV(HLLV) 400-999 copies/mL (aHR:1.446, 95%CI:1.228-1.702), and experiencing LLV only once or intermittently (intermittent low-level viremia, iLLV). Conclusions　There are many factors affecting the survival time of patients with low-level viremia. High attention should be paid and comprehensive consideration should be given to formulating treatment and follow-up management measures to improve patients' quality of life.

Objective:To construct a nomogram model for predicting the risk of leukopenia among tuberculosis patients receiving anti-tuberculosis therapy.Methods:A total of 2 681 tuberculosis patients admitted to the affiliated Dongyang Hospital of Wenzhou Medical University from Jan 2013 to Jun 2024，were enrolled in this study. All cases received first line anti-tuberculosis treatment and were randomly divided into training（ n=1 876）and validation groups（ n=805）at a ratio of 7∶3. The endpoint was the occurrence of leukopenia during anti-tuberculosis therapy. In the training group，the predictors were screened by Lasso regression and multivariable Logistic regression analysis，and used to establish a nomogram prediction model. The discrimination power，fitness and clinical applicability were evaluated using the receiver operating characteristic（ROC）curve，calibration curve and decision curve analysis，respectively. Several machine learning models based on different methods（random forest，support vector machine，extreme gradient boosting and naive Bayes）were also constructed in the validation group. Results:There were 15.0%（273/1 876）and 15.9%（128/805）of cases developing leukopenia during anti-tuberculosis therapy in the training group and validation groups，respectively. Following Lasso regression analysis，the multivariable Logistic regression analysis showed that age ≥65 years（ OR=2.997，95% CI 2.185-4.128），alcohol consumption（ OR=4.803，95% CI 3.502-6.593）and diabetes（ OR= 5.459，95% CI 3.914-7.621）were risk factors related to the occurrence of leukopenia；while the higher levels of baseline hemoglobin（ OR=0.979，95% CI 0.971-0.987）and platelet count（ OR=0.996，95% CI 0.995-0.998）were protective factors. Based on these five factors，a nomogram prediction model was developed. The areas under ROC curve（AUCs）were 0.836（95% CI 0.810-0.863）and 0.818（95% CI 0.776-0.860）in the training group and the validation group，respectively. Moreover，this model had good fitness and clinical applicability. The discrimination power of nomogram model was comparable to those of machine learning models. Conclusion:The established nomogram model in this study has good discrimination power，calibration ability and clinical applicability for predicting the risk of leucopenia in tuberculosis patients undergoing anti-tuberculosis therapy.

Objective:To construct a nomogram model for predicting the risk of leukopenia among tuberculosis patients receiving anti-tuberculosis therapy.Methods:A total of 2 681 tuberculosis patients admitted to the affiliated Dongyang Hospital of Wenzhou Medical University from Jan 2013 to Jun 2024，were enrolled in this study. All cases received first line anti-tuberculosis treatment and were randomly divided into training（ n=1 876）and validation groups（ n=805）at a ratio of 7∶3. The endpoint was the occurrence of leukopenia during anti-tuberculosis therapy. In the training group，the predictors were screened by Lasso regression and multivariable Logistic regression analysis，and used to establish a nomogram prediction model. The discrimination power，fitness and clinical applicability were evaluated using the receiver operating characteristic（ROC）curve，calibration curve and decision curve analysis，respectively. Several machine learning models based on different methods（random forest，support vector machine，extreme gradient boosting and naive Bayes）were also constructed in the validation group. Results:There were 15.0%（273/1 876）and 15.9%（128/805）of cases developing leukopenia during anti-tuberculosis therapy in the training group and validation groups，respectively. Following Lasso regression analysis，the multivariable Logistic regression analysis showed that age ≥65 years（ OR=2.997，95% CI 2.185-4.128），alcohol consumption（ OR=4.803，95% CI 3.502-6.593）and diabetes（ OR= 5.459，95% CI 3.914-7.621）were risk factors related to the occurrence of leukopenia；while the higher levels of baseline hemoglobin（ OR=0.979，95% CI 0.971-0.987）and platelet count（ OR=0.996，95% CI 0.995-0.998）were protective factors. Based on these five factors，a nomogram prediction model was developed. The areas under ROC curve（AUCs）were 0.836（95% CI 0.810-0.863）and 0.818（95% CI 0.776-0.860）in the training group and the validation group，respectively. Moreover，this model had good fitness and clinical applicability. The discrimination power of nomogram model was comparable to those of machine learning models. Conclusion:The established nomogram model in this study has good discrimination power，calibration ability and clinical applicability for predicting the risk of leucopenia in tuberculosis patients undergoing anti-tuberculosis therapy.

Objective:To investigate the value of T 1ρ mapping in the assessment of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods:Forty HCM patients and 16 healthy volunteers who underwent CMR examination between December 2021 and May 2022 were prospectively enrolled. T 1ρ mapping, pre-and post-contrast T 1 mapping, and gadolinium contrast-enhanced delayed enhancement (LGE) imaging were performed in HCM patients, while T 1ρ mapping and T 1 mapping were performed in volunteers. HCM patients were further divided into LGE-positive (LGE+) and LGE-negative (LGE-) groups based on the presence or absence of LGE. The T 1ρ and pre-contrast T 1 values of the left ventricular myocardium of HCM patients and volunteers were measured, and the extracellular volume fraction (ECV) of the left ventricular myocardium of HCM patients was measured using pre-and post-contrast T 1 mapping. One-way ANOVA was used to compare the T 1ρ and pre-contrast T 1 values among the LGE+, LGE-, and volunteer groups, and pairwise comparisons were further corrected using the Bonferroni method. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of pre-contrast T 1 and T 1ρ values in distinguishing LGE+ and LGE- patients from volunteers. The chi-square test or Fisher′s exact probability test was used for categorical variable comparisons. Pearson correlation coefficient was used to evaluate the correlation between T 1ρ and pre-contrast T 1, and ECV. Results:There were no significant differences in age, gender, and body surface area among the LGE+, LGE-, and healthy control groups ( P>0.05). Compared to the HC group, both the T 1ρ value ( t=5.74, P<0.001) and the pre-contrast T 1 value ( t=3.99, P<0.001) increased in LGE positive group, as well as in the LGE negative group (T 1ρ: t=4.19, P<0.001; T 1: t=2.06, P<0.044). ROC analysis showed that the area under the curve (AUC) of T 1ρ and pre-contrast T 1 in distinguishing LGE+patients from healthy controls were 0.93 (sensitivity 84.0%, specificity 93.8%) and 0.87 (sensitivity 84.0%, specificity 87.5%), respectively. The AUC of T 1ρ and pre-contrast T 1 in distinguishing LGE-patients from healthy controls were 0.84 (sensitivity 86.7%, specificity 68.8%) and 0.68 (sensitivity 60%, specificity 68.8%), respectively. The correlation analysis showed that the T 1ρ value of the left ventricular myocardium was positively correlated with the pre-contrast T 1 value ( r=0.31, P=0.02) and ECV value ( r=0.38, P=0.02). Conclusion:Without the use of contrast agents, T 1ρ mapping shows good performance for myocardial replacement fibrosis and diffuse fibrosis in HCM patients.