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 predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma (MM).Methods:The clinical data of 12 MM patients who used plerixafor for stem cell mobilization in the First Affiliated Hospital of Guangxi Medical University from December 2019 to February 2021 were retrospectively analyzed. The changes of peripheral blood CD34-positive cell count and the collection status of stem cell in all patients before and after the mobilization of plerixafor were analyzed.Results:Twelve patients were included in this study. These patients were in international staging system (ISS) stage Ⅱ-Ⅲ, and the induction therapy was mainly VRD regimen. The CD34-positive cell count was increased after the use of plerixafor in all patients no matter which mobilization strategies were used before plerixafor. The CD34-positive cell count was 3.63/μl (0.72-13.53/μl) and 32.11/μl (8.52-53.68/μl) before and after the use of plerixafor, and the difference was statistically significant ( Z = -0.40, P<0.001); the median increasing time was 11.50 times (1.61-23.71 times). The mobilization failure occurred in 1 patient. The CD34-positive cell count in his blood was less than 1/μl before the use of plerixafor; though increased 11.83 times after the use of plerixafor, the CD34-positive cell count was still less than 10/μl. Pearson analysis showed that among the patients with CD34-positive cell count less than 4/μl before the use of plerixafor, there was a positive correlation in peripheral blood CD34-positive cell count before and after the use of plerixafor ( r = 0.80, P = 0.032). Conclusions:The peripheral blood CD34-positive cell count has a certain predictive value for the stem cell mobilization effect of plerixafor in MM patients.

Objective To evaluate the impact of cardiopulmonary resuscitation (CPR) training on the willingness to perform on-site rescue for patients with apnea and cardiac arrest. Methods Through questionnaire survey, the analyses on the differences in the results of evaluating various indicators in CPR Willingness Questionnaire in 364 willingness (including 14 recurrent training personnel) of Yunnan Emergency Center from January 2017 to June 2018 before and after CPR training were carried out in order to observe the impact of training on willingness CPR willingness. Results A total of 364 questionnaires were distributed and 364 valid questionnaires were recovered, with a recovery rate of 100%. Compared with those before the CPR training, the analyses of the contents of the questionnaire showed that the proportions of following 6 types of volunteer who were reluctant to implement CPR on site begore training were significantly lower after CPR training [no confidence in their own operational skills: 20.3% (74/364) vs. 83.2% (303/364), being impossible to identify the patients requiring CPR: 25.5% (93/364) vs. 87.1% (317/364), fear of mouth-to-mouth artificial respiration to contract infectious diseases: 30.2% (110/364) vs. 82.4% (300/364), worried about chest compressions leading to bone fractures: 23.3% (85/364) vs. 86.8% (316/364), worried about the inaccurate positioning of chest compressions: 12.4% (45/364) vs. 82.4% (300/364) and fear of taking legal responsibility: 14.3% (52/364) vs. 89.8% (327/364)], and the differences were statistically significant (all P < 0.05); after training, the following 3 kinds of proportions of carrying out CPR were much higher than those before training [volunteers were willing to implement CPR on site for strangers: 83.2% (303/364) vs. 54.9% (200/364), volunteers were willing to implement CPR on site for friends, colleagues, classmates and other acquaintances: 83.5% (304/364) vs. 58.2% (212/364), volunteers were willing to implement CPR on site for family members: 84.6% (308/364) vs. 61.8% (225/364)], the differences being statistically significant (all P < 0.05). Conclusion CPR training for volunteers can improve their willingness to perform on-site rescue for patients with apnea and cardiac arrest, but there are still partial barriers of CPR willingness for strangers.

Objective To explore the impact of local lipiodol deposition in liver of miniature pigs on the shape and size of the necrotic area after microwave ablation (MWA).Methods Ten healthy miniature pigs were selected and equally divided into experimental group and control group (each n=5).In experimental group,transcatheter hepatic arterial embolization with lipiodol was done before microwave ablation,while only standard microwave ablation was performed in control group.Immediate post-ablation CT images were obtained.Long-axis diameter (LAD),short-axis diameter (SAD),sphericity index (SI=SAD/LAD) and volume of ablation zone were calculated.The size and shape of the ablated areas were compared between two groups.Results The mean LAD,SAD,SI and volume of ablation zone in experimental group ([4.21 ± 0.52]cm,[2.87±0.38]cm,0.69±0.10,[18.72±6.08]cm3) were larger than those in control group ([3.71±0.42]cm,[2.19±0.42]cm,0.60±0.09,[9.44±2.29] cm3;all P＜0.05).Conclusion Local deposition of lipiodol in liver parenchyma of miniature pigs can help to produce larger and rounder necrosis in the ablation zone.

OBJECTIVE:To establish HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry for rapid determination of aconitine,mesaconitine,hypaconitine,benzoylaconitine,benzoylmesaconine and benzoylhypacoitine in rat plasma. METHODS:Internal standard lappaconitine was added into plasma sample,and methanol precipitated protein was used for pretreatment. HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry was adopted. HPLC condition was as follows as Sinochrom ODS-BP C18column,mobile phase consisted of acetonitrile-1% formic acid solution(50:50,V/V),the flow rate of 0.6 mL/min,sample size of 10 μL,column temperature of 25 ℃,automatic sampler temperature of 4 ℃. Mass spectrum scanning mode was full ion monitoring model,positive ion acquisition,mass charge ratios(m/z)of ion were 646.32(aconitine), 632.30(mesaconitine),616.31(hypaconitine),604.31(benzoylaconitine),590.29(benzoylmesaconine),574.30(benzoylhypacoitine), 585.31(internal standard). Six male Wistar rats were collected and given single dose of total alkaloid extract of Aconitum carmichaeli(4 mg/kg)intragastrically. Blood samples were collected before medication(0 h)and 0.5,0.75,1.25,1.5,2,4,6, 8,10,24 h after medication. Plasma concentration was determined and pharmacokinetic parameters were calculated by using PK-Solver V2.0 software. RESULTS:The linear range of 6 kinds of aconitum alkaloids in plasma were 0.1-10 μ g/L(r>0.992). The limit of quantitation was 0.1 μ g/L. Average recovery was higher than 75%,RSDs of intra-day and inter-day,matrix effects,stability test were all lower than 15%. The tmaxof 6 kinds of aconite alkaloids were about 1.2 h;t1/2were about 10 h;cmaxof monoestertype aconite alkaloids were higher than those of diester-type aconite alkaloids. CONCLUSIONS:Established HPLC-quadrupole/electrostatic field orbitrap high resolution mass spectrometry is accurate,sensitive,simple and rapid, and can be used for plasma concentration monitoring of 6 kinds of aconitum alkaloids.

Objective To understand effects of the interventional operation on thyroid,peripheral blood indexes and chromosomal aberrations (CA) of peripheral lymphocyte of children with congenital heart disease (CHD).Methods Follow-up studies were conducted in 70 child patients undergoing cardiac catheterization and 23 with open heart surgery as control from 2010 to 2013.Postoperative follow-up examinations included thyroid ultrasound,blood routine indexes and analyses of CAs.Results Difference in thyroid ultrasound abnormality rate was not statistically significant between children with cardiac catheterization and control group (40.0％ vs.43.5％,P ＞ 0.05).There was no significant difference in white blood cell (WBC) count between interventional group and control group (P ＞ 0.05).The effects of disease type and operation time on thyroid ultrasound and WBC count were not observed (P ＞ 0.05).The frequency of chromosome aberrations,including acentric fragment,dicentrics and translocation in interventional group [(0.76 ± 0.07) ％],was higher than in control group [(0.25 ± 0.07) ％,(Z =-3.631,P ＜ 0.05],and the rates of acentric fragment and translocation were also higher in interventional group (Z =-2.531,-2.397,P ＜ 0.05).Conclusions Effect of intervention therapy on thyroid structure and WBC count in children with CHD was not observed,but the genotoxic effects remain in children with cardiac catheterization.

Objective:To report a case of lung adenocarcinoma of stage Ⅳ with epidermal growth factor receptor (EGFR) mutation treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance,and to review the related literatures.Methods:A female patient without smoking history was diagnosed with lung adenocarcinoma (stage cT3N2M1 Ⅳ) with metastatic lesions in liver and bones by chest CT,lung puncture biopsy,and whole-body PET-CT.EGFR gene test reported mutation (19 del).Through treatment of overall survival,pemetrexed disodium for injection plus carboplatin injection,gemcitabine hydrochloride for injection plus cisplatin injection,paclitaxel for injection (albumin bound) single and with bevacizumab;the overall survival (OS) was assessed as 32 months.And the period of Erlotinib HCL Tablets showed 10 months of progressive-free survival (PFS).However,due to the metastatic lesions that suppressed biliary system in liver,hyperbilirubinemia emerged (total bilirubin 304 μmol · L-1,direct bilirubin 193 μmol · L-1).Bevacizumab was adopted and the syndrome relieved (total bilirubin 70 μmol · L-1,direct bilirubin 35 μmol · L-1),yielding three months of PFS.But the bilirubin level upgraded with total bilirubin of 908 μmol · L-1.The patient died because of hyperbilirubinemia.Results:10-month PFS occupied 1/3 of OS was acquired in the patients with EGFR-mutated lung adenocarcinoma (stage Ⅳ) after treated with Erlotinib HCL Tablets.Chemotherapy combined with bevacizumab acquired 3 months of PFS after hyperbilirubinemia emerged with drug resistance and multi-lines of chemotherapy.Conclusion:EGFR-TKIs are effective in treatment of lung adenocarcinoma with EGFR mutation;bevacizumab can inhibit the formation of vessels by targeting on VEGF under the circumstance of multiple drug resistance.Therefore,chemotherapy combined with bevacizumab can be used as the fifth-line of therapy in dealing with the hyperbilirubinemia induced by lung adenocarcinoma with liver metastasis.

Objective To investigate the changes and significance of serum C reactive protein (CRP) and calcitonin (PCT) levels in the elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods One hundred and twenty elderly patients with AECOPD in the respiration deplartment of our hospital from January 2013 to study One hundred and twenty elderly patients with AECOPD in our hospital from January 2013 to June 2015 were selected to conduct the study and performed the subgroup analysis according to the BODE index (body weight,dyspnea,airflow,motor function index),times of acute exacerbation within 1 year after treatment and recurrence time,and other 40 healthy subjects in the outpatient department were selected as the control group.The serum PCT and CRP levels were compared among various groups.Results Serum CRP and PCT levels in AECOPD patients with grade 1-4 of BODE index were significantly higher than those in the control group (P＜0.05),moreover in the intra-group comparison of serum CRP and PCT,the grade l＜grade 2＜grade 3＜grade 4,the differences were statistically significant (P＜0.05).Serum CRP and PCT had the significantly positive correlation with the grades of BODE index in AECOPD patients (r=0.482,0.317,P＜0.05).After treatment,serum CRP and PCT levels in AECOPD patients with recurrence occurred more than 3 months were significantly lower than those in the patients with recurrence occurred within 3 months,the difference was statistically significant (P＜0.05);serum CRP and PCT levels in the patients with more than once recurrence at 1 year after discharge from hospital were significantly higher than those in the patients with recurrence ≤once,the difference were statistically significant (P＜0.05).Conclusion The serum levels of CRP and PCT in the patients with AECOPD can reflect dyspnea,airflow limitation and motor function ability,and conducts the preliminary assessment on the patient's prognosis.

Objective To summarize the experience of applying choledochoscopy, duodenoscopy and laparoscopy, one-stage suturing of common bile duct, to treat cholecystolithiasis and choledocholithiasis that failed to respond to ordinary endoscopic sphincterotomy (EST). Methods Retrospectively analyzed the clinical data of twenty-five pa-tients with choledocholithiasis complicated with cholecystolithiasis. 25 cases of failure to endoscopic stone extraction underwent LC and laparoscopic common bile duct exploration with primary suture of (BD) from June 2013 to June 2015. Results One patient was converted to laparotomy with small incision. The other one had residual stones and therefore underwent a second EST. After the treatment, two patients developed hyperamylasemia, which was cured by conservative therapy; One patient had bile leakage, which was treated by percutaneous drainage with no serious complications and death. No long-term complication was found in a portion of patients followed up until now. Conclusion In properly selected patients of duodenoscopy management-failed, synchronous treatment of combined application of three endoscopies in laparoscopic surgery with primary suture of (BD) is feasible, effective and safe.

Objective:To explore the clinical value of remote ECG consultation for primary medical institutions. Methods:Remote ECG consultation data for medical institutions of different levels in Hubei Jianli county were sta-tistically analyzed.Results:In county hospitals of this area,there were 1334 cases of ECG consultation,the positive rate was 41.00% (547/1334),and the three abnormal ECG types with highest incidence rate were arrhythmia (27.29%),left ventricular hypertrophy (LVH,9.15%)and ST-T change (2.62%)in order;in rural health rooms of this area,there were 723 cases of ECG consultation,the positive rate was 55.19%(399/723),and the three ab-normal ECG types with highest incidence rate were arrhythmia (34.02%),ST-T change (11.07%)and LVH (5.39%)in order.Conclusion:The remote ECG consultation is easy to perform.It can rise the detection rate of transient abnormal ECG events in rural area,where is lack of ECG equipment and personnel,so it is worthy of ex-tending.