Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To explore the therapeutic effect and prognostic influencing factors of endovascular therapy for periprocedural acute ischemic stroke with large vessel occlusion(AIS-LVO)after cardiac surgery,and to analyze the pathological characteristics of thrombi leading to LVO.Methods This study retrospectively and consecutively enrolled patients who experienced AIS-LVO during the perioperative period of cardiac surgery at the Cardiovascular Surgery Department of Guangdong Provincial People's Hospital from June 1,2017,to March 31,2024.The patients were divided into a surgical group and a non-surgical group based on whether they received endovascular treatment.The clinical and imaging data of the patients were collected,including gender,age,hypertension,diabetes,history of smoking,low-density lipoprotein cholesterol,cardiac surgical methods(coronary artery bypass grafting,total arch replacement[TRA],cardiac valve replacement,other types of surgery[valve repair,atrial septal repair,ventricular septal repair,heart transplantation]),time from cardiac surgery to AIS onset,location of vascular occlusion(vertebral-basilar artery,right internal carotid artery,left internal carotid artery),National Institutes of Health stroke scale(NIHSS)score at the onset of stroke,time from stroke onset to puncture,stroke etiology(embolism,arterial dissection,atherosclerotic stenosis),and imaging data including Alberta stroke program early CT score(ASPECTS)of the anterior circulation,ASPECTS of the posterior circulation(pc-ASPECTS)and CT angiography,CT perfusion,etc.The thrombus samples were stained with hematoxylin-eosin and martius scarlet blue staining.According to the proportion of red blood cells(RBC)in the thrombus,the thrombi were classified as erythrocyte-rich thrombi(RBC proportion≥70%),mixed thrombi(RBC proportion 31%-69%),and fibrin-rich thrombi(RBC proportion≤30%).At 90d after stroke onset,the modified Rankin scale(mRS)was used for both outpatient and telephone follow-up.The mRS score 0-2 indicated a good prognosis,3-6 indicated a poor prognosis,and 6 points indicated death.Factors with P＜0.1 in univariate Logistic regression and those factors may influence the prognosis according to clinical experience were included and further analyzed with multivariate Logistic regression to analyze the 90 d prognostic influencing factors after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.Results A total of 102 patients who experienced AIS-LVO during the perioperative period of cardiac surgery(68 males,34females,with mean age of[58±14]years)were enrolled in this study,50 were in the non-surgery group and 52 in the surgery group.(1)Significant differences were observed between the surgical and non-surgical group in hypertension(32.7%[17/52]vs.54.0%[27/50],P=0.030),NIHSS score at stroke onset(12.3[12.3,21.8]vs.35.0[18.0,35.0],P＜0.01),vascular occlusion site(P=0.048),cardiac surgery type(P＜0.01),ASPECTS/pc-ASPECTS(9[8,9]vs.4[3,6],P＜0.01),favorable90-day prognosis rate(75.0%[39/52]vs.10.0%[5/50],P＜0.01)and 90-day mortality rate(7.7%[4/52]vs.68.0%[34/50],P＜0.01).Other clinical and imaging data showed no significant differences(all P＞0.05).In the surgery group,86.5%(45/52),7.7%(4/52),and 5.8%(3/52)patients were attributed to embolism,arterial dissection,and atherosclerotic stenosis,respectively.(2)Univariate Logistic regression analysis identified NIHSS score at stroke onset,TRA,endovascular therapy,and ASPECTS/pc-ASPECTS score as prognostic factors affecting the 90-day prognosis after stroke.Set the patient's 90-day prognosis(assign favorable prognosis as 1 and poor prognosis as 0)as dependent variable,incorporate factors with P＜0.1 in the univariate Logistic analysis and location of vascular occlusion in a multivariate Logistic regression analysis.The results showed that high NIHSS score on stroke onset(OR,0.86,95%CI 0.78-0.95,P=0.002)and non endovascular therapy(OR,6.93,95%CI 1.05-45.55,P=0.044)were independent risk factors of poor prognosis 90-day after stroke onset for AIS-LVO patients during the perioperative period of cardiac surgery.(3)Among 45 cardioembolic patients,thrombus samples from 33 patients were analyzed.The analysis revealed no erythrocyte-rich thrombi,3 mixed thrombi,and 30 fibrin-rich thrombi,with 12having a fibrin proportion exceeding 90%.Conclusion Endovascular therapy improved the prognosis and reduces mortality rate in patients with periprocedural AIS-LVO after cardiac surgery,and thrombi in these patients are predominantly fibrin-rich.

Objective:To investigate the correlation between arcuate fasciculus(AF),superior longitudinal fasciculus(SLF),inferior longitudinal fasciculus(ILF),and post-stroke aphasia(PSA)by diffusion tensor imaging(DTI).Method:Fourteen patients with post-stroke aphasia were included,while 18 healthy individuals with gender and age matching were recruited as controls.Western aphasia battery(WAB)and DTI were performed in two groups of participants.Result:Compared with normal healthy controls,aphasic patients had dominant side AF,SLF-Ⅱ,SLF-Ⅲ,and ILF damage,with a significant decrease in fiber FA value,fiber quantity,and fiber length(P<0.05).However,dominant side SLF-I,non dominant side AF,SLF-I,SLF-Ⅱ,and SLF-Ⅲ had no significant damage(P>0.05).The non-dominant side ILF fiber quantity of non-dominant side in the aphasic group was significantly lower than that in the healthy control group(P<0.05).However,there were no significant decrease in the FA value and fiber length between two groups(P>0.05).There was no significant correlation between specific single bundle fi-ber damage and WAB's AQ,spontaneous speech,auditory comprehension,repetition and naming scores(P>0.05).Conclusion:The injury of AF,SLF-Ⅱ,SLF-Ⅲ,and ILF in the dominant side of the brain is an important central mechanism for the occurrence of PSA.

Objective:To investigate the feasibility of thigh muscles segmentation in patients with Duchenne muscular dystrophy (DMD) using the TransUNet deep learning model on MRI.Methods:This was a cross-sectional study. From April 2023 to September 2024, the axial T 1WI imagings of 60 DMD patients, confirmed by genetic analysis at Northwest Women′s and Children′s Hospital, were enrolled in this retrospective study. Patients were divided into a training set ( n=48) and a test set ( n=12) at a ratio of 8∶2 using random sampling. Fat infiltration scores were assigned to 11 thigh muscles, including the rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, adductor longus, adductor magnus, gracilis, semimembranosus, semitendinosus, and biceps femoris long head. A total of 1 078 images were included (884 for training, 194 for testing).The 12 DMD patients in the test set were divided into groups G1 to G4, with 2, 4, 2, and 4 cases respectively, according to the total score of muscle fat infiltration from low to high. A TransUNet model was trained on the T 1WI to perform automatic segmentation of the 11 thigh muscles in both thighs. The segmentation performance of the TransUNet automatic segmentation model was evaluated using the Dice similarity coefficient (DSC), intersection over union (IoU), and average symmetric surface distance (ASSD), with the results of manual delineation by physicians as the gold standard. And one-way analysis of variance or the Kruskal-Wallis H test was used to compare the segmentation effects of the automatic segmentation model on the thigh muscles of children among G1 to G4. Results:The mean processing time for the automatic segmentation of all 11 muscles in both thighs per patient was (8.3±1.5) s. The DSC, IoU and ASSD in training set and in test set were 0.971±0.011, 0.948±0.019, 0.69 (0.55, 0.96) and 0.944±0.021, 0.900±0.038, 0.58 (0.55, 0.91), respectively. In the training set, the semitendinosus muscle achieved the best segmentation results (DSC 0.99, IoU 0.97, ASSD 0.52). In the test set, the sartorius muscle showed the best segmentation performance (DSC 0.96, IoU 0.93, ASSD 0.50). There were no statistically significant differences in the overall DSC, IoU, or ASSD of the automatic segmentation model across groups G1 to G4 ( P>0.05). Conclusions:The TransUNet automatic segmentation model can rapidly and accurately segment the bilateral thigh muscles in patients with DMD, and the segmentation performance demonstrated consistent among patients with different degrees of muscle fat infiltration.

Objective To assess the impact of freeze-drying and dry heat virus inactivation processes on the activity ofα2-macroglobulin(A2M)derived from human plasma Cohn fraction Ⅳ.Methods A2M derived from human plasma Cohn fraction Ⅳ was prepared and subjected to programmed freeze-drying with dry heat virus inactivation.The lyophilized products were evaluated for their appearance,water content,and validation of the viral inactivation process.The bioactivity of the products before and after lyophilization as well as before and after dry heat inactivation was determined via trypsin inhibition,and the comparisons were studied.Results The appearance of the lyophilized product was fluffy,and the water content was(5.83±0.45)％.The specific activities of the samples before and after lyophilization were(10.199±0.137)and(10.033±0.201)μg/mg,respectively,with no statistically significantdifference between the two groups(P＞0.05).The viral inactivation of the samples was carried out by using dry heat inactivation conditions at 100 ℃ for 30 min.After inactivation,the reduction was ≥5.125 LgTCID50/0.1 mL in Pseudorabies virus(PRV)titers,≥4.500 LgTCID50/0.1 mL in Sindbis virus(SinV)titers,≥6.375 LgTCID50/0.1 mL in encephalomyocarditis virus(EMCV)titers,and≥4.500 LgTCID50/0.1 mL in porcine parvovirus(PPV)titers.The specific activities of the samples before and after dry heat were(9.921±0.292)and(10.091±0.278)μ g/mg,respectively,with no statistically significant difference between the two groups.Conclusion A2M derived from human plasma Cohn fraction Ⅳ,when subjected to freeze-drying followed by dry heat inactivation at 100 ℃ for 30 minutes,can effectively inactivate viruses without altering the biological activity of the product.

Objective: To examine the mediating effect of resilience on AIDS-related stress and patient-reported outcome among elderly cases with HIV/AIDS, so as to provide the basis for promoting mental health and improving health outcomes of this population. Methods: From June to July 2024, elderly cases with HIV/AIDS receiving treatment in the infectious diseases department of a tertiary-level hospital in Sichuan Province and undergoing follow-up management at 12 community health service centers in Wuhou District, Chengdu City, Sichuan Province, were selected as study participants using convenience sampling method. Data on demographic information, duration since confirmed diagnosis and the most recent CD4+T lymphocyte count were collected through questionnaire surveys. The Chinese versions of the HIV/AIDS Stress Scale, the Chinese versions of the 10-item Connor-Davidson Resilience Scale, and the Patient-Reported Outcome Scale for Elderly HIV/AIDS Patients were used to assess AIDS-related stress, resilience, and patient-reported outcome, respectively. Structural equation modeling was performed using Mplus 8.3 software to analyze the mediating effect of resilience on AIDS-related stress and patient-reported outcome. The Bootstrap method was employed to test the significance of the mediating effect. Results: A total of 424 elderly HIV/AIDS cases were included, with a mean age of (62.04±8.73) years. Among them, 315 (74.29%) were males and 109 (25.71%) were females. The median scores were 23.00 (interquartile range, 11.00) points for AIDS-related stress, 30.00 (interquartile range, 7.00) points for resilience, and 363.45 (interquartile range, 53.03) points for the total score of patient-reported outcome. Resultsof the mediation effect analysis revealed that AIDS-related stress had a direct negative effect on patient-reported outcome (β=-0.608, 95%CI: -0.742 to -0.465). It also exerted an indirect negative effect on patient-reported outcome through the mediating role of resilience (β=-0.258, 95%CI: -0.364 to -0.158), with the mediating effect accounting for 29.79% of the total effect. Conclusion AIDS-related stress among elderly cases with HIV/AIDS can directly or indirectly negatively affect patient-reported outcome through resilience.

Objective:To evaluate the prevalence of hepatitis C virus (HCV) infection among patients attending a comprehensive tertiary hospital in Beijing and to pinpoint the key demographics for anti-HCV screening.Methods:A comprehensive retrospective analysis was undertaken, examining data from 631 424 patients who underwent anti-HCV testing between 2017 and 2023. Testing for anti-HCV was conducted using the Abbott i2000 fully automated chemiluminescent immunoassay analyzer. HCV nucleic acid testing was performed with the Roche Cobas AmpliPrep/Cobas TaqMan 96 fluorescent quantitative PCR system, while HCV genotyping was achieved through sequencing.Results:The positive rate of HCV antibodies demonstrated a gradual decline over the years, decreasing from 1.62% in 2017 to 1.01% in 2023. The overall positive rate stood at 1.36% (8 574/631 424), with a nucleic acid testing rate of 59.24% (5 079/8 574) and a nucleic acid positive rate of 34.28% (1 741/5 079). The majority of anti-HCV positive patients came from the department of hepatology (12.17%), followed by hepatobiliary surgery (3.03%), emergency medicine (1.68%), cardiovascular medicine (1.24%) and ophthalmology clinic (1.23%). Notably, the anti-HCV positive rate was significantly elevated in the ≥40 years old group compared to the <40 years old group, with statistical significance ( χ2=1 892.577, P=0.000). The highest anti-HCV positive rates were observed within the 60-69- and 80-99-years old brackets (both at 1.85%), while the peak HCV RNA positive rate was recorded in the 50-59 years old group (27.08%). Females exhibited a significantly higher positive rate (18.53%) than males (15.75%) ( χ2=8.066, P<0.01). When anti-HCV levels surpassed 9 S/CO, the HCV RNA positive rate was notably high, exceeding 38.97%. Intriguingly, at antibody levels ranging from 15 to 16 S/CO, the HCV RNA positive rate climbed to a maximum of 56.17%. Conclusions:This study has successfully identified the key populations for anti-HCV screening: Patients aged over 40, particularly female patients within the 50-69 age bracket; Patients in hepatology, hepatobiliary surgery, emergency medicine, cardiovascular medicine and ophthalmology departments.

Objective:To explore the predictive value of baseline serum levels of hepatitis B virus (HBV) RNA for HBeAg seroconversion in chronic hepatitis B (CHB) subjects with advanced fibrosis/compensated cirrhosis undergoing tenofovir disoproxil fumarate (TDF) therapy.Methods:A case-control study was conducted on 141 patients with CHB combined with advanced fibrosis/compensated cirrhosis who were treated with TDF and tested at Peking University People′s Hospital from January 2015 to December 2020. Patients were divided into HBeAg seroconversion (16 cases) group and non-seroconversion (59 cases) group based on whether HBeAg seroconversion occurred at 240 weeks after treatment. The patients were divided into HBeAg positive and negative groups at baseline (75 and 66 cases, repectively) and at 12 weeks treatment (61 and 80 cases, repectively). The baseline serum levels of relevant indicators were analyzed. HBV RNA levels were measured at baseline and at 240 weeks after treatment. The correlation between HBV RNA and HBV DNA was analyzed using Pearson correlation analysis, and the predictive value was evaluated using the receiver operating characteristic (ROC) curve.Results:For the 75 HBeAg-positive patients at baseline, 21.3% (16/75) achieved HBeAg seroconversion. The HBV DNA and HBV RNA in the HBeAg-positive group were significantly higher than that in the HBeAg-negative group (all P<0.001). Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV RNA ( P<0.05). Pearson correlation analysis showed that serum HBV RNA levels were positively correlated with HBV DNA in both baseline and 12 weeks HBeAg-negative group and HBeAg-positive group, respectively (baseline: r=0.718, 0.794, P<0.001; 12 weeks: r=0.689, 0.750, P<0.001). ROC curve showed that baseline levels of HBV RNA could be used as a predictor of HBeAg seroconversion in CHB patients with advanced fibrosis/compensated cirrhosis treated with TDF. The area under curve was 0.781, the sensitivity was 75.0%, and the specificity was 78.0%. Conclusion:Baseline serum levels of HBV RNA has a predictive value for HBeAg seroconversion in CHB patients with advanced fibrosis/compensated cirrhosis treated with TDF.

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases, and its diagnosis heavily relies on imaging biomarkers. This paper integrates core pathological markers, such as amyloid β (Aβ)-positron emission tomography (PET), tau-PET, structural magnetic resonance imaging, and fluorodeoxyglucose-PET, with the latest advancements in novel imaging biomarkers, including inflammation, synaptic imaging, and cerebrovascular injury-related markers, based on the Aβ proteinopathy, tau proteinopathy, neurodegeneration, inflammation, α-synuclein and vascular brain injury biomarkers (AT 1T 2NISV) framework proposed by the 2024 Alzheimer′s Association diagnostic guidelines. With the development of machine learning and artificial intelligence technologies, future research should focus on enhancing the specificity of imaging biomarkers and developing precise diagnostic models for comorbidities to better address the heterogeneity and complex pathological features of AD.

Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P＜0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P＜0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.