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 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 investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of Toxoplasma gondii, so as to provide insights into for toxoplasmosis prevention and control. Methods ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the T. gondii PRU strain at a dose of 1 × 10⁵ tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic T. gondii infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with T. gondii cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of T. gondii infections on the number of cysts was examined in the mouse brain. Mice were orally administered with T. gondii cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with T. gondii tachyzoites at a dose of 1 × 10⁵ tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain. Results Following infection with T. gondii tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain (F = 11.94, P < 0.01) on day 30 post-infection with T. gondii tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with T. gondii tachyzoites and oocysts than in those infected with cysts (all P values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively (F = 0.42, P > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively (F = 1.63, P > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively (F = 4.82, P < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T (P < 0.01). Following oral administration of 20 T. gondii cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection. Conclusions There is a higher possibility of developing chronic T. gondii infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic T. gondii infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.

Objective:To investigate the neuropsychological and imaging features of patients with posterior cortical atrophy (PCA).Methods:Patients of PCA, dementia with Lewy bodies (DLB), typical Alzheimer′s disease (t-AD) who were diagnosed in the Department of Neurology, Huashan Hospital, Fudan University from September 27, 2019, to September 24, 2021 were enrolled, and the normal controls who visited the Outpatient and Physical Examination Centers of Huashan Hospital, Fudan University and Rizhao People′s Hospital at the same time were enrolled, too. Neuropsychological assessments, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT data of the 4-group subjects were collected. Variance analysis was used to compare the differences in neuropsychological performance among the 4 groups, and the imaging features of PCA patients were summarized.Results:Eleven PCA patients, 17 DLB patients, 31 t-AD patients, and 11 normal controls were included in the study. The cognitive function of patients in the PCA group [Mini-Mental State Examination (MMSE) score 13.52±1.81; Montreal Cognitive Assessment (MoCA) score 7.06±1.72] was significantly impaired compared to the normal control group (MMSE score 27.85±1.75, t=-6.561, P<0.001; MoCA score 23.60±1.59, t=-7.968, P<0.001]. However, there was no statistically significant difference compared to the DLB group and the t-AD group. Patients in the PCA group exhibited more severe impairments in attention, executive function, and language compared to the DLB group (Trail Making Test A score: 298.86±16.16 vs 110.07±18.62, t=9.980, P<0.001; Trail Making Test B score: 305.51±18.89 vs 230.34±23.59, t=2.865, P=0.024; Boston Naming Test score: 8.67±1.53 vs 15.66±1.56, t=-2.682, P=0.013) and the t-AD group (148.91±12.77, t=7.071, P<0.001; 200.78±19.34, t=3.789, P=0.004; 15.15±1.05, t=-2.544, P=0.016). Scores for visuospatial function [PCA group: 1(0, 1), normal control group: 3(3, 3), Z=-4.023, P<0.001] and visual perception [PCA group: 0(0, 1), normal control group: 35(34, 36), Z=-3.704, P<0.001] were significantly lower in the PCA group compared to the normal control group. The cranial MRI findings of PCA patients showed atrophy of the parietal and occipital lobes, with less obvious atrophy of the medial temporal lobe, which can be distinguished from t-AD. 18F-fluorodeoxyglucose PET/CT of the PCA patients showed a relative reduced glucose metabolism in the bilateral parietal lobe, occipital lobe and posterior cingulate gyrus, while the 18F-florbetapir PET/CT showed deposition of amyloid protein in the bilateral frontal lobe, parietal lobe, temporal lobe, and cingulate gyrus. Conclusions:PCA patients exhibit neuropsychological characteristics of visuospatial dysfunction, along with impairments in various cognitive domains such as memory, attention, and executive functions. The typical MRI feature is parietal occipital lobe atrophy, and the PET/CT findings are consistent with metabolic changes in AD.

Objective:To understand the epidemiological characteristics of central obesity and pre-central obesity and influencing factors in residents in Jilin Province, and provide reference for the prevention and control of central obesity and pre-central obesity.Methods:Based on the results of early screening and comprehensive intervention program in high-risk groups of cardiovascular disease in Jilin dyring 2017-2018, a total of 11 903 participants aged 35-75 years in 6 project areas in Jilin were included as the survey subjects for physical examination, laboratory test and questionnaire survey. The prevalence of central obesity and pre-central obesity in populations with different characteristic and health status were analyzed by χ2 test, trend χ2 test, F-test. Multivariate logistic regression model was used for influencing factor analysis. Results:The central obesity rate was 33.35% (3 970/11 903), the standardized rate was 31.73%, the pre-central obesity rate was 28.79% (3 427/11 903), the standardized rate was 28.86%. Multifactor analysis results showed that being rural resident ( OR=1.99, 95% CI: 1.78-2.23), being woman ( OR=1.76, 95% CI: 1.57-1.97), 65-75 years old ( OR=1.21, 95% CI: 1.03-1.45), senior high school and technical secondary school education level ( OR=1.38, 95% CI: 1.17-1.63), annual family income >100 000 yuan ( OR=1.65, 95% CI: 1.20-2.26), overweight ( OR=9.27, 95% CI: 8.26-10.41), obesity ( OR=82.82, 95% CI: 62.63-109.52), normal high blood pressure ( OR=1.49, 95% CI: 1.27-1.74), hypertension ( OR=1.70, 95% CI: 1.42-2.04), diabetes ( OR=2.30, 95% CI: 1.94-2.73), dyslipidemia ( OR=1.33, 95% CI: 1.18-1.50) were positively related to the risk for central obesity and pre central obesity. Conclusions:The prevalence rates of central obesity and pre central obesity in residents in Jilin were at high levels, being rural resident, being woman, older age, senior high school and technical secondary school education level, high income, overweight and obesity, normal high blood pressure and hypertension, diabetes, dyslipidemia were risk factors for central obesity and pre-central obesity in Jilin.

Constructing a doctor-patient community with a shared future requires efforts from both the medical supply side and the patient demand side, with special attention to the needs of patients. Continuously meeting and improving the needs of patients is the starting point, ultimate goal, and evaluation standard for constructing a doctor-patient community with a shared future. Therefore, this paper proposed the proposition of "what patients need", that is, what needs do patients have and how to meet their needs. The fundamental needs of patients are to diagnose and treat diseases and recover from illness, which are specifically manifested in the demands to narrate the disease’s feelings, the willingness to participate in medical decision-making, the experience of diagnosis and treatment in the process of medical treatment, and the satisfaction evaluation of the hospital’s performance appraisal. On the basis of clarifying the needs of patients, this paper proposed the paths and methods to meet patients’ needs, and provided new ideas for constructing a doctor-patient community with a shared future.

Objective To put forward suggestions for improving the scheme of general practice for functional communities from the perspective of supply and demand,guide the efficient use of the resources of general practice by the communities,and incorporate the general practice of communities into hierarchical diagnosis and treatment management. Methods In July 2021,stratified random sampling was employed to conduct the questionnaire surveys of the young and middle-aged (demand side) and the general practitioners (supply side),respectively.SPSS 20.0 was used for data analysis. Results The two sides had the same cognition about the main reasons for not signing a contract with a family doctor,which were the lack of knowledge about general practitioners and the lack of face-to-face communication opportunities.They had the same response about the form of services,with high acceptance of medical services via WeChat,outpatient consultation,and the internet.There were differences in service content between the two sides.The top three demands of the young and middle-aged were appointment registration and referral in superior hospitals,medication guidance,and massage,acupuncture,and moxibustion.The top service self-rated by general practitioners was personalized guidance and report interpretation of physical examination,and the bottom was massage,acupuncture,and moxibustion. Conclusions The general practice varies between the demand and supply sides.General practitioners should be encouraged to enter and learn functional communities and provide personalized services,thus improving the general medical service in functional communities.
General Practice ; Surveys and Questionnaires

Objective:To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma.Methods:Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 μm (small particle size) and 300~500 μm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results:The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P 1 month=0.012, P 3 month=0.009, P 6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant ( P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant ( P=0.182). Conclusions:In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.

Objective:To establish and internally validate a visualized model for predicting the severity of acute pancreatitis (AP).Methods:From September 1st 2017 to August 31st 2020, 600 patients with AP diagnosed in the First Affiliated Hospital of Kunming Medical University were enrolled. According to the Atlanta classification of AP, the 600 patients were divided into severe acute pancreatitis (SAP) group (128 cases) and non-severe acute pancreatitis (NSAP) group (472 cases). The general clinical data (age, gender, body mass index, etc), laboratory indicators (fasting blood glucose, urea nitrogen, creatinine, etc.), complicated with ascites or pleural effusion, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores and bedside index of severity in acute pancreatitis (BISAP) score between the two groups were compared. The potential predictors of SAP were screened with least absolute shrinkage and selection operator (LASSO). The screened predictors were included in the multivariate logistic regression analysis to establish the logistic regression model. The operation characteristic curves of the model, APACHE Ⅱ scores and BISAP were drawn, the discriminative capability of the model was evaluated by comparing the area under the curve (AUC). Calibration, Hosmer-Lemesshow test and decision curve analysis (DCA) were used to evaluate the accuracy and clinical practicability of the prediction model. Bootstrap was used for internally validation of the model. Independent sample t test, Wilcoxon test and chi-square test were used for statistical analysis. Results:The difference of gender composition ratio between SAP and NSAP group was statistically significant ( χ2=4.092, P<0.05). The fatality rate of SAP group was higher than that of NSAP group(21.1%, 27/128 vs. 0, 0/472); the length of hospital stay of SAP group was longer than that of NSAP group((20.33±16.21) d vs. (8.42±4.26) d); the hospitalization cost, fasting blood glucose level, urea nitrogen level, creatinine level, C-reactive protein(CRP) level, D-dimer level, fibrinogen level, white blood cell count, percentage of neutrophils, neutrophil-lymphocyte ratio, APACHEⅡ and BISAP scores, the incidence of complicated with pleural effusion or ascites and the constituent ratio of alcoholic etiology of SAP group were all higher than those of NASP group (44 837.58 yuan (23 017.73 yuan, 102 579.77 yuan) vs. 12 301.46 yuan (8 649.26 yuan, 18 823.88 yuan); (10.48±4.84) mmol/L vs. (8.45±4.80) mmol/L; (8.80±6.50) mmol/L vs. (4.90±2.33) mmol/L; (139.56±127.75) mmol/L vs. (80.05±38.54) mmol/L; (187.33±87.25) mg/L vs. (90.81±82.53) mg/L; 5.19 mg/L (2.96 mg/L, 8.52 mg/L) vs.1.29 mg/L (0.53 mg/L, 2.87 mg/L); 6.13 mg/L (4.64 mg/L, 7.31 mg/L) vs. 4.58 mg/L (3.50 mg/L, 5.98 mg/L); (14.87±5.82)×10 9/L vs. (11.79±4.86)×10 9/L; 0.84±0.12 vs.0.78±0.12; 13.16±7.57 vs. 8.77±7.28; 9.80±6.09 vs. 3.79±2.59; 2.12±0.89 vs. 1.04±0.78; 65.6%, 84/128 vs. 12.9%, 61/472; 70.3%, 90/128 vs. 20.3%, 96/472; 18.8%, 24/128 vs. 11.4%, 54/472); serum albumin level, blood calcium level, and hematocrit level of SAP group were all lower than those of NSAP group ((30.86±4.95) g/L vs. (37.14±5.44) g/L; (1.98±0.31) mmol/L vs. (2.16±0.20) mmol/L; (42.40±8.67)% vs.(44.30±6.45)%), and the differences were all statistically significant ( χ2=99.403, t=8.235, Z=-13.330, t=4.239, 10.759, 5.207 and 11.227, Z=-11.406 and -6.234, t=6.097, 4.829, 6.011, 10.899 and 12.395, χ2=152.604, 117.563 and 4.757, t=-11.788, -6.180 and -2.310, all P<0.05). LASSO regression analysis screened out four predictors of CRP, urea nitrogen, D-dimer and ascites. The results of multivariate logistic regression analysis showed that CRP (odds ratio ( OR)=1.009, 95% (confidence interval) CI 1.006 to 1.012), urea nitrogen( OR=1.185, 95% CI 1.097 to 1.280), D-dimer( OR=1.166 95% CI 1.082 to 1.256), ascites ( OR= 4.848, 95% CI 2.829 to 8.307) were the independent predictors of SAP (all P<0.01). The AUC of the model (0.895 , 95% CI 0.865 to 0.926) was higher than those of the APACHE Ⅱ(AUC=0.835, 95% CI 0.791 to 0.878)and BISAP score (AUC=0.803, 95% CI 0.760 to 0.846), and the differences were statistically significant ( Z=2.578 and 4.466, both P<0.05). The results predicted by the model in the calibration chart and the Hosmer-Lemesshow test were highly consistent with the results of actual clinical observation. When the probability of SAP in the model was 10% to 95%, the DCA curve of the model was higher than the two extreme lines, which had certain clinical practical value. After bootstrap internal validation, the model had a high discrimination ability (AUC=0.892), and its predicted AP severity curve was still in good agreement with the actual clinical AP severity curve. Conclusion:The prediction model established based on CRP, urea nitrogen, D-dimer and ascites can predict the severity of AP, and help doctors to make more scientific clinical decision.

With the development of detection methods, various biomarkers of liver cancer have been detected constantly, which is of great significance for the early diagnosis and real-time monitoring of liver cancer after treatment. Based on the differences in the sensitivity and specificity of different biomarkers, exploration of the value of diverse biomarkers in the diagnosis and prognosis assessment of liver cancer can provide an important reference for clinicians to scientific and rational application of distinct biomarkers.