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.

BACKGROUND:The shoulder joint,as a non-weight-bearing joint of the human upper limb,is considered a perfect compromise between flexibility and stability.The traditional experimental mechanics research of shoulder joints has some limitations due to the complexity of internal structure,measurement techniques and ethical issues.The finite element analysis method is applied to the research of shoulder joints,which provides valuable reference conclusions for the discussion of shoulder joint diseases and the decision of surgical methods. OBJECTIVE:To review the status of finite element research in the field of the shoulder joint,and to put forward the prospect of future research. METHODS:The finite element analysis method was used to search the literature on shoulder joint complex-related diseases in PubMed,Web of Science,WanFang and CNKI databases by computer.Chinese search terms were"shoulder joint,finite element analysis,rotator cuff injury,glenoid labrum,shoulder joint replacement".English search terms were"FE,should joint,glenohumeral joint,rotator cuff tears,glenoid labrum,shoulder arthroplasty".The search period was mainly from January 2010 to January 2023.Some important documents were also tracked,retrieved and read. RESULTS AND CONCLUSION:(1)With the open network of model data and the establishment of relevant model databases,finite element research has become more and more standardized and reproducible.(2)The widely validated finite element model of the shoulder joint deepens our understanding of the shoulder field to enable more efficient clinical decision-making.(3)With the continuous development of computer technology and software development,future finite element research is bound to become an indispensable practical tool for clinical scientific research.

Objective To investigate the experience of intrauterine device(IUD)removal in patients with cervical cancer after radiotherapy.Methods A total of 23 patients with cervical cancer after radiotherapy underwent abdominal ultrasound guided hysteroscopic removal of IUD in our department from January 2020 to December 2022.For vaginal and/or cervical adhesions,blunt separation of adhesions was performed by using hysteroscope head or curved forceps under abdominal ultrasound guidance.If it was difficult to separate the adhesions for hysteroscope head entering the uterine cavity,a probe was inserted into the uterine cavity under ultrasound guidance,and the cervical canal was gradually expanded to 6-caliber dilation rod.Then the hysteroscope was inserted again into the uterine cavity.For obvious cervical atrophy that was tough in which cervical forceps could not be used to clamp the cervix,a 1-0 absorbable suture line was used to suture the anterior and/or posterior lips of the atrophied cervix at the top of the vagina,with an assistant firmly pulling and fixing the cervix.Results There were 4 cases of vaginal partial adhesions and cervical contracture,10 cases of cervical contracture,and remaining 9 cases having no vaginal adhesions and cervical contracture.Under hysteroscopy,there were 3 cases of cervical adhesions,2 cases of endometrial polyps,1 case of submucosal uterine fibroids,2 cases of uterine abscess,2 cases of incarcerated IUD,and remaining 13 cases having normal uterine cavity morphology.All the 23 cases of IUD were successfully removed by using abdominal ultrasound guided hysteroscopy(circular shaped in 12 cases,uterine shaped in 6 cases,V-shaped in 2 cases,Y-shaped in 1 case,T-shaped in 1 case,and umbrella shaped in 1 case).The surgical time was(19.2±10.9)min,and there were no complications such as false passage formation,uterine perforation,organ damage,massive vaginal bleeding,transurethral resection of the prostate syndrome,infection,embolism,or shock.The 23 cases were followed up for 2-24 months postoperatively,with a median of 12 months.One case continued concurrent radiotherapy and chemotherapy,3 cases continued post-loading radiotherapy,1 case continued chemotherapy,and 2 cases received targeted treatment(distant metastasis).The remaining 16 cases recovered well in regular reviews without complications such as abdominal pain,fever,or vaginal bleeding.Conclusions If the size and location of the cancer lesion do not affect the removal of IUD after radiotherapy for cervical cancer,it should be removed as soon as possible.The application of abdominal ultrasound guided hysteroscopy in IUD removal in patients with cervical cancer after radiotherapy is safe and feasible to a certain extent.

Objective     To analyze the clinical efficacy and survival outcome of totally thoracoscopic redo mitral valve replacement and evaluate its efficiency and safety. Methods     The clinical data of patients with totally thoracoscopic redo mitral valve replacement in Guangdong Provincial People’s Hospital between 2013 and 2019 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to determine the risk factors for postoperative death. Results     There were 48 patients including 29 females and 19 males with a median age of 53 (44, 66) years. All the procedures were performed successfully with no conversion to median sternotomy. A total of 15, 10 and 23 patients received surgeries under non-beating heart, beating heart and ventricular fibrillation, respectively. The in-hospital mortality rate was 6.25% (3/48), and the incidence of early postoperative complications was 18.75% (9/48). Thirty-five (72.92%) patients had their tracheal intubation removed within 24 hours after the operation. The 1- and 6-year survival rates were 89.50% (95%CI 81.30%-98.70%) and 82.90%(95%CI 71.50%-96.20%), respectively. Age>65 years was an independent risk factor for postoperative death (P=0.04). Conclusion     Totally thoracoscopic redo mitral valve replacement is safe and reliable, with advantages of rapid recovery, reducing blood transfusion rate, reducing postoperative complications and acceptable long-term survival rate. It is worthy of being widely popularized in the clinic.

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 establish and evaluate a fluorescent antibody to membrane antigen (FAMA) method for detecting antibodies against varicella-zoster virus (VZV) based on Vero E6 cells. 【Methods】 Based on the adapted VZV-Oka-E6 strain that VZV-Oka live attenuated varicella vaccine strain grew in Vero E6 cells, Vero E6 cells were infected with VZV-Oka-E6 of three different doses (10^4.65, 10^4.95 and 10^5.25 TCID50), and the cytopathic effect was observed under a microscope to determine the optimal infection dose of VZV-Oka-E6 strain. Then the detectable sensitivity of the infected cell antigen slides prepared after fixing the infected cells with different fixatives was compared to determine the optimal fixative. As a result, the FAMA method based on Vero E6 cells for the determination of neutralizing anti-VZV has been developed. The established FAMA assay was used to detect the international standard for varicella zoster immunoglobulin with different titers to determine the sensitivity of the assay. The specificity of the assay was evaluated by detecting specific antibodies against human herpes simplex virus (HSV) type 1 and type 2. The neutralizing anti-VZV antibodies of the international standard for varicella zoster immunoglobulin were detected using VZV-infected cell antigen slides prepared in the same batch and four different batches, respectively, to determine the intra-assay repeatability and inter-assay repeatability. The international standard for varicella zoster immunoglobulin with three known titers was detected to evaluate the relative accuracy of this assay. The anti-VZV titers in 20 apheresis plasma samples were determined with the newly established FAMA test and ELISA test, respectively, and the detection results of the two methods were compared using Spearman’s correlation test. 【Results】 The optimal infection dose of the VZV-Oka-E6 strain in FAMA assay was determined to be 10^5.25 TCID50, and acetone precooled at -20℃ was used as the fixative. The FAMA test has a high sensitivity with a detecting limit of 31.25 mIU/mL for neutralizing anti-VZV titers. The negative result was observed when detecting herpes simplex virus (HSV) type 1 and 2 specific antibodies. The international standard for varicella zoster immunoglobulin was detected by VZV infected cell antigen slides prepared in the same batch and 4 different batches, with the coefficient of variation being 29.95% and 26.71%, respectively. The detection value of the international standard for varicella zoster immunoglobulin with three different titer levels was consistent with their theoretical value. The correlation coefficient of the detection results of 20 apheresis plasma samples by the FAMA test and ELISA test was 0.268. 【Conclusion】 The VZV FAMA assay has good sensitivity, specificity, repeatability, and relative accuracy in detecting neutralizing anti-VZV titers. It can be applied for detecting neutralizing anti-VZV titers in apheresis plasma samples as well as the varicella-zoster immunoglobulin (VZIG) preparations.

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 evaluate the efficacy of hybrid ablation through compared with thoracoscopic epicardial ablation. Methods    In this study, 108 patients with all long-standing persistent atrial fibrillation (LSPAF) received thoracoscopic epicardial ablation (TEA) after enrollment. There were 82 males and 26 females at age of 56.5±9.4 years. After blanking-period, patients off antiarrhythmic therapy with sinus rhythm were divided into a hybrid ablation (HA) group (50 patients) and a TEA group (58 patients). Only patients in the HA group received catheter ablation after randomization subsequently. In at least two-year observation period, cardiovascular risk factors were observed in all groups’ patients. Results    The mean follow-up duration was 17.3-41.8 (26.9±6.1) months and there was no significant difference between two groups [8.2-40.6 (27.5±5.7) months in the HA group and 17.3-41.8 (26.4±6.7) months in the TEA group]. The off antiarrhythmic agents (AADs) sinus rhythm rate was significantly higher in the HA group than that in the TEA group at the time of postoperative 6, 12, 24 and 36 months ［96.0%, 90.0%, 83.7%, 83.7% versus 79.3%, 75.9%, 67.3%, 63.1%, HR=0.415 (95%CI 0.206-0.923)]. Conclusion    We can conclude that the efficacy of two-staged hybrid ablation for LSPAF is superior to thoracoscopic epicardial ablation alone. Patients can obtain benefit from a supplemental radiofrequency catheter ablation after blanking-period of surgical ablation, instead of those without a supplemental ablation.

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.

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.