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.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Objective:To establish the lung blast injury model in mice, detect the proteomic changes of lung in mice at different time points, and explore the mechanism of lung blast injury.Methods:A total of 60 healthy male C57BL/6 mice were randomly (random number) divided into the control group, 12-h group after thorax blast, 24-h group, 48-h group, 72-h group and 1-week group ( n=10 each group). Experiments were carried out in the animal laboratory of the General Hospital of the Northern Theater Command. The model of lung blast injury in mice was established by using a self-developed precision blast device, and the lung tissue injury situation was evaluated by gross observation and HE staining. The proteins in mouse lung tissue were quantitatively analyzed based on LC-MS/MS proteomic technology, and the differentially expressed proteins were screened. On this basis, bioinformatics tool was used to analyze proteomic changes. Results:After lung blast injury, scattered bleeding spots could be observed on the surface of lung tissue of mice, and the bleeding points were gradually increased with time, showing a patchy distribution, and the symptoms were the most severe at 24 h. The results of HE staining showed that the normal tissue structure of alveoli disappeared at 12 and 24 h under light microscopy with diffuse bleeding in the alveolar cavity, infiltration of a large number of inflammatory cells, increased interstitial exudate, thickened alveolar wall, and collapsed and merged alveolar cavity. A total of 6 861 proteins were identified by LC-MS/MS in lung tissue samples of mice after thorax blast, and 608 differentially expressed proteins were quantified, of which 227, 140, 202, 258 and 71 differential proteins were at 12 h, 24 h, 48 h, 72 h, and 1 week, respectively. According to GO analysis, 130 biological process subtypes including cell adhesion, extracellular matrix tissue and collagen fibril tissue were obtained. Besides, 66 cellular component involving extracellular exosomes, extracellular matrix and cytoplasm were obtained. And 43 molecular functional subclasses such as extracellular matrix structure composition, actin binding and antioxidant activity were obtained. KEGG analysis yielded 24 pathways including ECM-receptor interactions, focal adhesions and PI3K-Akt signaling pathway across the endothelium.Conclusions:Differentially expressed protein combinations are also different at different time points in the early stage after lung blast in mice, and the injury mechanism is complicated. The lung blast injury is the most serious at 12-24 h after blast and produces significant inflammatory response.

Objective: To investigate the effect of glycogen synthase kinase 3β (GSK3β) on the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 (Aβ31-35) in HT22 cells. Methods: HT22 mouse hippocampal cells were divided into control group, Aβ31-35 group and LiCl+Aβ31-35 group by random number table method in the present study. Cells were synchronized to G0/G1 phase by 1% serum starvation for 1 hour (circadian time 0 (CT0)). Cell viability was detected by the cell counting kit-8 assay. The mRNA expression of clock gene Bmal1 was examined by real-time PCR at different CT times. The expression of GSK3β and BMAL1 protein was detected by Western blotting. Results: Compared with the control group, Aβ31-35 induced the decreased expression of Bmal1 mRNA; The expression of both Bmal1 mRNA and BMAL1 protein was decreased significantly at CT20 (Bmal1 mRNA: 0.38±0.06 vs 0.83±0.08, t=4.549, P=0.001; BMAL1 protein: 0.67±0.04 vs 1.00±0.04, t=5.943, P<0.001). In the Aβ31-35 group, GSK3β activity was increased and the ratio of phosphorylated GSK3β^S9 to GSK3β was decreased compared to the control group (0.66±0.08 vs 1.02±0.14, t=2.217, P=0.025). Aβ31-35 decreased the viability of HT22 cells (71.85%±6.20% in the Aβ31-35 group vs 98.14%±2.68% in the control group, t=3.891, P=0.006), and the GSK3β inhibitor LiCl pretreatment effectively reversed the decline of the viability induced by Aβ31-35 (90.74%±5.74% in the LiCl+Aβ31-35 group vs 71.85%±6.20% in the Aβ31-35 group, t=3.412, P=0.010). LiCl (in the LiCl+Aβ31-35 group) increased the expression of Bmal1 mRNA and BMAL1 protein significantly at CT20 compared with the Aβ31-35 group (Bmal1 mRNA: 0.72±0.05 vs 0.38±0.06, t=4.378, P=0.001; BMAL1 protein: 0.90±0.04 vs 0.67±0.04, t=4.052, P=0.002). Conclusion Increased GSK3β activity involved in the decreased expression of Bmal1 induced by Aβ31-35 in HT22 cells.

To explore the application effect of team-based learning (TBL) model in functional experiment teaching. A clinical case related to the animal experiment was selected and distributed to students through Internet before class. Individual tests for students were conducted in class to assess their understanding for the case. Then group tests were carried out, which were completed by in-group discussion. Finally, the clinical case was analyzed within group. The teaching process possesses several characteristics and advantages in helping students retrieve literature, cultivate their spirit of cooperation, their ability of clinical practice and so on, but it also has some shortcomings and deficiencies. Therefore, this paper summarizes the advantages and disadvantages of TBL teaching in functional experiment teaching based on existing experience so as to promote a broader application of TBL in our medical education.

Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.

Objective To evaluate the diagnostic value of A-F mnemonic performed by sonographers with limited experience in patients with acute chest pain. Methods This was a prospective observational study. Bedside cardiac ultrasound for patients with chest pain was performed by six sonographers with limited experience using A-F mnemonic, evaluating indexes including aortic dissection(A), both ventricles (B), regional wall motion abnormality (RWMA), left ventricular ejection fraction (LVEF) ≤ 50％ (C ,contractility), dimensions (D), pleural and pericardial effusion (E) and further abnormalities (F). Afterwards, experienced cardiac sonographers performed the same examinations, and the difference in the time of ultrasound examination was calculated. The diagnosis of experienced sonographers were referred as the control group, and kappa test was applied to analyze the sensitivity, specificity, positive predictive value and negative predictive value. Results There were 245 cases eligible for study, and 20 cases were excluded. Finally 225 cases of acute chest pain were included in the analysis, containing 158 fatal chest pain and 67 low-risk chest pain. The experienced sonographers diagnosed 20 cases of ascending aortic dissection, 5 cases of right ventricular dilatation, 72 cases of RWMA, 12 cases of LVEF ≤ 50％, 45 cases of left ventricular dilatation, 6 cases of hydropericardium, and 6 cases of other abnormalities. The consistency between beginners and experienced sonographers were as follows:completely same (hydropericardium, Kappa=1.000), highly consistent (ascending aortic dissection, Kappa=0.853, right ventricular dilatation, Kappa=0.931, and other abnormalities, Kappa=0.829), moderately consistent (RWMA, Kappa=0.768, LVEF ≤ 50％, Kappa=0.713 and left ventricular dilatation, Kappa=0.766). The sensitivity and negative predictive value of RWMA and LVEF ≤ 50％ and the positive predictive value of left ventricular dilatation in the beginner sonographers were lower than those in the experienced sonographers. Conclusions A-F mnemonic was a simple and practical way for the beginner sonographers to perform bedside cardiac ultrasound. It was of significant value in making correct diagnosis of most acute chest pain patients and providing quick and reliable information for clinicians.

Objective To explore the diagnosis,treatment and prognosis of neuroblastoma in children. Methods The clinical data of 36 children With neuroblastoma admitted to Department of Pediatric Surgery,Henan Pro﹣vincial People＇s Hospital betWeen August 2013 and August 2018,Were retrospectively analyzed. The patients included 22 males and 14 females With the age of 1 month－13 years old[( 20. 0 ± 18. 5)months]. TWenty－one cases of neu﹣roblastoma originated from the adrenal glands,the other 15 cases from the sympathetic ganglion( including 7 cases in retroperitoneum,6 cases in postmediastinum,and 2 cases in neck). Fifteen patients in loW risk and intermediate risk groups underWent primary surgery before multiple chemotherapy,While other 21 cases in high risk groups underWent chemotherapy until the mass could be removed completely,then continuely underWent multiple chemotherapy. Results Of the 36 patients,23 cases(63. 9%)had a radical resection,13 patients underWent palliative resection and 2 pa﹣tients Were treated With vascular repair during surgery(abdominal aorta in 1 patient,inferior vena cava in 1 patient). TWenty－seven patients had effective in formation and 16 patients survived,during folloW－up,12 patients belonged to stage Ⅰ－Ⅲ disease,2 patients stage Ⅳ disease and 2 patients stage Ⅳs disease,respectively. Four cases underWent re－operation due to disease recurrence,then they underWent chemothearopy,and 3 patients Were survival With tumor. Conclusions Neuroblastoma is a highly malignant pediatric cancer accompanied With a high rate of metastasis on ini﹣tial diagnosis. Radical resection is an effective therapeutic strategy for improving the survival rate. If radical resection is impractical,palliative resection combined With chemotherapy can significantly prolong patients＇ survival time. And a better prognosis is achieved if it can be early diagnosed and treated timely.

OBJECTIVETo analyze the common hemorrhage sites during laparoscopic rectal cancer surgery in order to take reasonable prevention and management.

METHODSClinical data of 355 rectal cancer patients who underwent laparoscopic total mesorectal excision in Shanxi Provincial People's Hospital from January 2012 to December 2014 were retrospectively analyzed. Common bleeding sites, blood loss, and hemostasis time were recorded. According to the date of operation, patients were divided into 2012 group (91 cases), 2013 group (122 cases) and 2014 group(142 cases). Hemorrhage rates were compared among three groups.

RESULTSNo significant differences were observed in the baseline data among the three groups(all P>0.05). The location in the order of the hemorrhage rate from high to low was seminal vesicle tail (63.0%, 131/208), inferior mesenteric vessels (27.3%, 97/355), Toldt's space (24.2%, 86/355), lateral rectal ligaments (12.1%, 43/355) and post-rectal spatial (8.2%, 29/355). According to the blood loss, post-rectal spatial[(14.1±7.1) ml], inferior mesenteric vessels [(12.7±6.1) ml] and seminal vesicle tail [(12.4±6.5) ml] were ranked in top three. The hemostasis time of seminal vesicle tail [(11.5±6.6) minutes] and post rectal spatial [(10.3±7.8) minutes] was longer than the others. Compared with 2012 group, shorter operative time [(205±50) minutes vs. (235±55) minutes, t=4.296, P=0.001], less blood loss [(35±19) ml vs. (81±24) ml, t=16.243, P=0.001] and lower hemorrhage rate [Toldt's space: 7.7%(11/142) vs. 39.6%(36/91), inferior mesenteric vessels: 9.2%(13/142) vs. 44.0%(40/91), post-rectal spatial: 0.7%(1/142) vs. 15.4%(14/91), lateral rectal ligaments: 2.1%(3/142) vs. 29.7%(27/91) and seminal vesicle tail: 50.6%(41/81) vs. 79.6%(43/54)] were found in 2014 group. The decline of hemorrhage rate in seminal vesicle tail was the slowest (χ=11.792, P=0.003).

CONCLUSIONSThe common hemorrhage sites during the laparoscopic rectal cancer surgery are inferior mesenteric vessels, Toldt's space, lateral rectal ligaments, post rectal spatial and seminal vesicle tail. Appropriate preventive measures can ameliorate the intraoperative bleeding significantly, however, more attention should be paid to the seminal vesicle tail during operation because of its higher hemorrhage rate, more blood loss and difficult hemostasis.