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 evaluate the efficacy of staged carotid artery stenting and coronary artery bypass grafting in the treatment of coronary heart disease complicated with carotid stenosis. Methods The clinical data of patients with coronary heart disease and carotid stenosis treated in Fuwai Hospital from November 2019 to September 2021 were retrospectively analyzed. All patients underwent staged carotid artery stenting and coronary artery bypass grafting. The incidence and risk factors of severe complications such as myocardial infarction, cerebral infarction and death during the perioperative period and follow-up were analyzed. Results A total of 58 patients were enrolled, including 47 males and 11 females with an average age of 52-77 (64.2±5.6) years. No complications occurred before coronary artery bypass grafting. There was 1 myocardial infarction, 1 cerebral infarction and 1 death after the coronary artery bypass grafting. The early complication rate was 5.2%. During the follow-up of 18.3 months, 1 cerebral infarction and 2 deaths occurred, and the overall complication rate was 10.3%. According to Kaplan-Meier survival curve analysis, patients with symptomatic carotid stenosis (log-rank, P=0.037) and placement of close-cell (log-rank, P=0.030) had a higher risk of postoperative ischemic cerebrovascular event, and patients with previous cerebral infarction had a higher risk of postoperative severe complications (log-rank, P=0.044). Conclusion Staged carotid artery stenting and coronary artery bypass grafting is safe and feasible for the treatment of coronary heart disease complicated with carotid stenosis.

In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Objective:To compare the accuracy and efficacy of robot assisted and navigation assisted pedicle screw fixation.Methods:Retrospective analysis of 764 patients with lumbar spine disorders who underwent internal fixation treatment at the Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, from June 2017 to April 2023 were performed. They were divided into the Renaissance group (212 cases), the Tinavi group (301 cases), and the S8 navigation group (251 cases), according to the method of assisted placement of pedicle screws. The operation time, fluoroscopy time, X-ray radiation dose, intra-operative blood loss, accuracy of screw placement, screw revision rate, pain visual analogue scale (VAS), Oswestry disability index (ODI) and postoperative infection rate were compared among the three groups.Results:922 screws were placed in the Renaissance group, 1,260 screws in the Tinavi group, and 1,044 screws in the S8 navigation group. The accuracy of clinically acceptable pedicle screw placement was 92.08% (849/922), 99.68% (1,256/1,260), and 99.43% (1,038/1,044) in the three groups, respectively, with the Renaissance group being smaller than the Tinavi group and the S8 group (χ 2=90.334, P<0.001; χ 2=68.446, P<0.001), and the Tinavi group and the S8 group had no statistically significant difference (χ 2=0.380, P=0.537). The operation time of the three groups was 173.64±62.23 min, 177.11±60.85 min, 176.02±60.93 min, and the intraoperative blood loss was 118.16±58.26 ml, 121.84±55.91 ml, 123.62±59.84 ml, respectively, and the differences between the groups were not statistically significant ( P>0.05). The fluoroscopy time of the three groups was 8.73±2.92 s, 10.67±2.85 s, and 11.31±2.89 s, and the X-ray radiation doses were 18.83±7.41 μSv, 20.40±7.60 μSv, and 22.88±7.47 μSv, respectively, with statistically significant differences between the groups and the two comparisons ( P<0.05). All patients were given follow-up for 3-30 months. Three cases in the postoperative Renaissance group underwent screw revision for nerve root irritation due to screw penetration of the pedicle cortex, and none of the other two groups underwent screw revision. Postoperatively, one case in the Renaissance group and one case in the Tinavi group had superficial infections, which were cured after prolonged antibiotic use. At 3 months postoperatively, the VAS scores for leg pain in the Renaissance group, the Tinavi group, and the S8 navigation group were 3.52±1.14, 3.59±1.12, and 3.39±1.16, and the VAS scores for back pain were 3.54±1.14, 3.57±1.12, and 3.51±1.15, respectively; the ODI scores were 12.48%±4.53%, 12.01%±4.57%, and 12.28%±4.60%, and none of the differences between the groups were statistically significant ( P>0.05). Conclusion:The accuracy of screw placement by the Tinavi robot was comparable to that of the S8 navigation, and both were superior to that of the Renaissance robot; the fluoroscopy time and radiation dose of the Renaissance robot were smaller than those of the Tinavi robot, which was smaller than that of the S8 navigation. The early efficacy of robotics and navigation-assisted pedicle screw internal fixation for lumbar spine disorders is similar.

OBJECTIVE: To explore the safety and effectiveness of one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation in the treatment of ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. METHODS: A clinical data of 20 patients with ankylosing spondylitis kyphosis combined with acute thoracolumbar spine fracture, who were treated with one-stage posterior eggshell osteotomy and long-segment pedicle screw fixation between April 2016 and January 2022, was retrospectively analyzed. Among them, 16 cases were male and 4 cases were female; their ages ranged from 32 to 68 years, with an average of 45.9 years. The causes of injury included 10 cases of sprain, 8 cases of fall, and 2 cases of falling from height. The time from injury to operation ranged from 1 to 12 days, with an average of 7.1 days. The injured segment was T ₁₁ in 2 cases, T ₁₂ in 2 cases, L ₁ in 6 cases, and L ₂ in 10 cases. X-ray film and CT showed that the patients had characteristic imaging manifestations of ankylosing spondylitis, and the fracture lines were involved in the anterior, middle, and posterior columns and accompanied by different degrees of kyphosis and vertebral compression; and MRI showed that 12 patients had different degrees of nerve injuries. The operation time, intraoperative bleeding, intra- and post-operative complications were recorded. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were used to evaluate the low back pain and quality of life, and the American spinal cord injury association (ASIA) classification was used to evaluate the neurological function. X-ray films were taken, and local Cobb angle (LCA) and sagittal vertical axis (SVA) were measured to evaluate the correction of the kyphosis. RESULTS: All operations were successfully completed and the operation time ranged from 127 to 254 minutes (mean, 176.3 minutes). The amount of intraoperative bleeding ranged from 400 to 950 mL (mean, 722.5 mL). One case of dural sac tear occurred during operation, and no cerebrospinal fluid leakage occurred after repair, and the rest of the patients did not suffer from neurological and vascular injuries, cerebrospinal fluid leakage, and other related complications during operation. All incisions healed by first intention without infection or fat liquefaction. All patients were followed up 8-16 months (mean, 12.5 months). The VAS score, ODI, LCA, and SVA at 3 days after operation and last follow-up significantly improved when compared with those before operation ( P<0.05), and the difference between 3 days after operation and last follow-up was not significant ( P>0.05). The ASIA grading of neurological function at last follow-up also significantly improved when compared with that before operation ( P<0.05), including 17 cases of grade E and 3 cases of grade D. At last follow-up, all bone grafts achieved bone fusion, and no complications such as loosening, breaking of internal fixation, and pseudoarthrosis occurred. CONCLUSION One-stage posterior eggshell osteotomy and long-segment pedicle screw fixation is an effective surgical procedure for ankylosing spondylitis kyphosis combined with acute thoracolumbar vertebral fracture. It can significantly relieve patients' clinical symptoms and to some extent, alleviate the local kyphotic deformity.
Humans ; Male ; Female ; Animals ; Adult ; Middle Aged ; Aged ; Spinal Fractures/surgery* ; Pedicle Screws ; Spondylitis, Ankylosing/surgery* ; Quality of Life ; Retrospective Studies ; Egg Shell/injuries* ; Thoracic Vertebrae/injuries* ; Lumbar Vertebrae/injuries* ; Kyphosis/surgery* ; Osteotomy ; Fracture Fixation, Internal/methods* ; Fractures, Compression/surgery* ; Treatment Outcome

Objective:To explore the clinicopathological characteristics and prognosis of pancreatic gastrointestinal interstitial tumors(pGISTs).Methods:Three cases of pGISTs diagnosed in the Affiliated Tumor Hospital of Guangxi Medical University from August 2015 to October 2019 were analyzed retrospectively. Relevant literatures at home and abroad were searched and reviewed through PubMed, China knowledge Network, Wanfang and VIP databases. The sex, age, tumor size, tumor location, cystic or solid tumor, mode of treatment, mitosis, gene mutation, survival status and survival time were recorded, and the correlation between tumor cystic-solid characteristics and clinicopathological parameters was analyzed. Kaplan-Meier′s method was used to calculate the overall survival (OS) rate and disease-free survival (DFS) rate. Univariate and multivariate Cox regression models were used to analyze the independent risk factors affecting the prognosis of pGISTs.Results:In this group, 3 cases were combined with 71 cases reported in the literature, and a total of 74 cases of pGISTs were included. Among them, 36 cases were male and 38 were female, the age of onset was 55(19-84) years, and the diameter of the tumor was 8 cm(2-35 cm). The tumor location of 71 patients was recorded by literature; 30 cases (42.3%) were located in the head of the pancreas. The solid-cystic characteristics of tumor in 63 patients were recorded by literature, and 33 cases (52.4%) were solid. The mode of treatment of 74 patients was recorded, and 60 cases (81.1%) underwent radical resection. The mitosis figures of 59 patients were recorded, and 33 cases (55.9%) were <5/50 high power field of vision (HPF). The gene mutation of 14 patients was recorded, and 11 cases (78.6%) were c-kit exon gene mutation. Correlation analysis showed that the cystic-solid characteristics of the tumor were significantly correlated with tumor location, tumor diameter and mitosis figures, but not with age, sex, histological type, Ki-67 index and modification National Institutes of Health(mNIH) classification. The 5-year OS rate of 51 patients after radical resection was 88.8%, and the 5-year DFS rate was 60.3%. The 1-year OS rate of patients receiving palliative treatment was 51.9%, and the 1-year fatality rate was 33.3%. Univariate Cox regression analysis showed that male ( P=0.083), mitosis figures >5/50 HPF ( P=0.008)and CD 34 negative ( P=0.055)were risk factors for postoperative recurrence of pGISTs, while multivariate Cox regression analysis showed that mitosis figures >5/50 HPF ( P=0.023)was an independent risk factor for the prognosis of pGISTs. Kaplan-Meier survival analysis showed that patients with mitosis figures ≤5/50 HPF had a higher survival rate ( P=0.0003), but there was no significant difference on prognosis between patients with 10/50 HPF and >10/50 HPF( P=0.3075). Conclusions:pGISTs usually occured in the head of pancreas, and the tumor volume was usually found to be large. The main treatment was radical operation, and the main mutation type was exon mutation of c-kit gene. Nuclear fission image figures >5/50HPF was an independent risk factor for postoperative recurrence.

ObjectiveTo investigate the safety and efficacy of re-hepatic resection (rHR) versus radiofrequency ablation (RFA) in the treatment of recurrent hepatocellular carcinoma (RHCC) in Asia through a meta-analysis. MethodsPubMed, CNKI, and Wanfang Data were searched for related studies published up to June 15, 2020. Two reviewers independently searched for the articles and extracted related data, and RevMan 5.4.1 was used to perform the meta-analysis. ResultsA total of 2 randomized controlled trials and 18 retrospective cohort studies met the inclusion criteria and involved 2903 patients with RHCC from Asian countries. The mortality rate in the perioperative period was 2% in the rHR group and 0 in the RFA group, and the incidence rate of perioperative complications was 22.4% in the rHR group and 3.3% in the RFA group. The 1-, 3-, and 5-year overall survival rates were 92.3%, 66.3%, and 51.1%, respectively, in the rHR group and 91.4%, 69.2%, and 39.9%, respectively, in the RFA group. The 1-, 3-, and 5-year disease-free survival rates were 67.9%, 48.3%, and 34.4%, respectively, in the rHR group and 57.5%, 27.9%, and 14.0%, respectively, in the RFA group. The Meta-analysis showed that there was no significant difference in overall survival rate between the two groups (hazard ratio ［HR］=089, 95% confidence interval ［CI］: 0.77-1.02, P=0.10), while the rHR group had a significantly higher disease-free survival rate than the RFA group (HR=0.79, 95% CI: 0.72-0.87, P＜0.001). ConclusionCurrent evidence shows that rHR may help to achieve a higher disease-free survival rate than RFA in the treatment of RHCC, while rHR and RFA have a similar overall survival rate.

Primary liver cancer is one of the most common malignant tumors in the world, and hepatocellular carcinoma accounts for the majority of liver cancer. Hepatectomy is one of the most important treatment methods, but the high postoperative recurrence rate is the leading cause of treatment failure, which seriously reduces the long-term survival rate and reduces quality of life. Therefore, preventing the recurrence of liver cancer is an important part of treatment. At present, there is no standard program for the treatment of hepatocellular carcinoma to prevent recurrence after surgery, most of the treatment programs include transarterial chemoembolization, antiviral therapy, traditional Chinese medicine treatment, targeted therapy, immunity therapy, etc., which has certain clinical significance in preventing recurrence. This paper reviewed the research progress on preventing recurrence of hepatocellular carcinoma after surgery, which may provide guidance for the clinical study.

Objective:To study the impact of preoperative serum HBV DNA levels on prognosis of hepatocellular carcinoma (HCC) patients undergoing hepatectomy with curative intent.Methods:The clinical data of patients with HCC treated by hepatectomy with curative intent at the Guangxi Medical University Cancer Hospital from January 2010 to December 2016 were retrospectively analyzed. According to the preoperative serum HBV DNA levels, patients were divided into three groups: the control group (HBV DNA negative), the low load group (<10 4 copy/ml) and the high load group (≥10 4 copy/ml). The clinical data of these patients were collected and long-term survival outcomes of these patients were followed-up. The Kaplan-Meier method was used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among the three groups. Using the Barcelona clinic liver cancer classification (BCLC), patients with different serum HBV DNA levels were further divided into three subgroups: stage 0/A, stage B and stage C. The OS and RFS rates of patients in each of these subgroups were compared. Results:Of 1 180 patients who were enrolled in the study, there were 1 024 males and 156 females, aged (48.6±10.8) years. The 1-, 3- and 5-year OS rates for patients in the control group ( n=258) were 91.5%, 79.3% and 74.9%, respectively; while those in the low load group ( n=289) were 87.2%, 68.6% and 61.6%, respectively; and those in the high load group ( n=633) were 85.4%, 68.9% and 60.7%, respectively. The 1-, 3- and 5-year OS rates in the control group were significantly better than those in the low load group and the high load group ( P<0.05). The 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). Subgroup analysis showed that in the BCLC 0/A subgroup ( n=786) the 1-, 3- and 5-year OS rates in the control group were significantly better than those in the high load group ( P<0.05). In the BCLC B subgroup ( n=181), the 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). In the BCLC C subgroup ( n=214), there were no significant differences in the 1-, 3- and 5-year OS and 1-, 2- and 3-year RFS rates among the three groups ( P>0.05). Conclusion:For HCC patients undergoing hepatectomy with curative intent, the higher the preoperative serum HBV-DNA level, the worse the long-term survival outcomes.

Objective:To investigate the clinical impact factors of liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma (HCC).Methods:Patients who underwent hemihepatectomy due to HCC from Sep 2013 to Sep 2018 were included in the study. Liver volumes were calculated by perioperative simulations to analyze the influencing factors of postoperative liver regeneration, and to compare the albumin bilirubin (ABLI) score and the end-stage liver disease (MELD) score at weeks 1, 5, 9, and 13 after operation.Results:A total of 163 patients were included, of which 13 developed postoperative liver failure. The median liver regeneration rates at 1, 5, 9 and 13 weeks after operation were 22.0%, 32.2%, 33.7% and 35.4%, respectively. Multivariate analysis showed that remnant liver volume (RLV) <611.1 cm 3, %RLV and liver cirrhosis were the influencing factors of liver regeneration. ALBI score and MELD score were lower in the low regeneration group compared to the high regeneration group in the first 5 weeks after operation. Conclusion:RLV and cirrhosis are influential factors in postoperative liver regeneration. Liver regeneration proceeded rapidly within 1 week and slowed down until week 5.