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 effects of dual task training assisted by a lower limb rehabilitation robot on lower extremity mobility and the walking ability of stroke survivors.Methods:Sixty-one stroke survivors were randomly divided into a control group and an experimental group with 30 in the control group and 31 in the experimental group. In addition to routine exercise training and physical therapy, both groups were given cognitive-motor dual task training 5 times a week for 3 weeks. But only in the experimental group was the dual task training assisted by a lower limb rehabilitation robot. Both groups′ lower limb motor function, walking ability, cognition, balance and ability in the activities of daily living were evaluated before and after the experiment using the Fugl-Meyer lower extremity assessment (FMA-LE), functional ambulation categories (FAC), the digital span test (DST), the Berg Balance Scale (BBS) and the Modified Barthel Index (MBI). Additionally, 6 survivors of a right hemisphere stroke from the experimental group received cognitive-motor dual task training both with and without the robotic assistance alternately. Near-infrared functional brain imaging was applied before and after the intervention, and the functional network connectivity of the resting brains was analyzed.Results:After the intervention the average FMA-LE, FAC, BBS and MBI scores had improved in both groups, with the improvement in the experimental group significantly better than in the control group on average. In terms of cognition there was no significant difference in the DST forward and backward assessment results between the two groups. The analysis of brain network functional connectivity showed that the intensity of functional connectivity between the left prefrontal cortex (PFC) and the left premotor cortex and supplementary motor cortex (PMC/SMA) increased significantly more, on average, after training assisted by the robot.Conclusion:Dual task training with the assistance of a lower limb rehabilitation robot can effectively improve the lower limb motor function, walking, balance and ability in the activities of daily living of stroke survivors. Enhanced functional connection of the PFC and the PMC/SMA in the healthy hemisphere induced by the robot may be the cause.

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.

Parkinson′s disease (PD) is the most common age-related neurodegenerative disease, which has the effects on the patients′ quality of life and brings a huge burden to the society and family. The pathological feature of PD is the abnormal accumulation of alpha-synuclein (α-syn) in the brain of substantia nigra-striatum, mediating the death of dopaminergic neurons. However, further studies have found that α-syn mediates the abnormal function of astrocytes leading to the destruction of the blood-brain barrier and the release of inflammatory factors caused by microglia, which are related to the pathogenesis of PD. Therefore, neurons, glial cells, and blood vessels as a whole named neurovascular unit can better reflect the pathophysiological environment of PD and reveal the PD pathogenesis. Studies have detected the ways of α-syn transmission, such as prion-like, tunneling nanotubes, exosomes, are connected with the pathogenesis and progression of PD. The Braak stage and the prospective cohort of early PD provide a view that the peripheral α-syn to the central nervous system may be an another important way to mediate the pathogenesis and progression of PD. The research about the abnormal aggregation and spread of α-syn can provide the new theory for the pathogenesis of PD and the new disease modifying therapy of PD. This article reviews the role of abnormal aggregation and transmission of α-syn in the pathogenesis of PD.

【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.

Idiopathic rapid eye movement (REM) sleep behavior disorder is recognized as a prodromal stage of α-synucleinopathies such as Parkinson′s disease, Lewy body dementia and multiple system atrophy. It is important to timely identify early predictors that can predict early conversion into α-synucleinopathies. This review provided an update on classic and novel early predictors of α-synucleinopathies in patients with idiopathic REM sleep behavior disorder and provided a comprehensive understanding on the phenotypic transformation of the disease.

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 observe the dynamic changes of thyroid hormone levels and thyroid autoimmune antibodies in pregnant women in Xinjiang Uygur Autonomous Region during pregnancy, and to investigate the significance of repeated screening of thyroid function in different gestational ages.Methods:A retrospective study was carried out of pregnant women who completed thyroid function screening in Clinic, People's Hospital of Xinjiang Uygur Autonomous Region from January 2015 to December 2017, and the test results of thyroid stimulating hormone (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TGAb) were collected and analyzed of their changes during pregnancy. Pregnant women were divided into 2 different gestational age groups by the age limit of 30, the changes of thyroid dysfunction rate with pregnancy were analyzed, and the clinical significance of repeated screening in different pregnancy stages was discussed. Results:Changes of thyroid-related indicators with pregnancy: first, second, and third trimesters were 404,725, and 767 cases, respectively; TSH level in the third trimester (2.76 mU/L) was significantly higher than those in the first and second trimesters (2.55, 2.36 mU/L, P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the FT 4 and FT 3 levels decreased gradually with pregnancy ( P < 0.05); the positive rate of TPOAb was significantly higher in the first and second trimesters than that in the third trimester ( P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the positive rate of TGAb decreased gradually with pregnancy ( P < 0.05). Comparison of abnormal rate of TSH in different gestational ages: the first, second, and third trimesters were 352, 664, 735 cases, respectively; the abnormal rate of TSH in the overall study was statistically significant at different stages of pregnancy (χ 2=31.627, P < 0.05), the first trimester was significantly higher those in the second and third trimesters ( P < 0.05). In pregnant women aged ≥30 years old, the abnormal rate of TSH in the first trimester was significantly higher than those in the second and third trimesters ( P < 0.05); in pregnant women aged < 30 years old, the abnormal rate of TSH in the first trimester was significantly higher than that in the third trimester ( P < 0.05). There were no significant differences in the abnormal rate of TSH in the first, second, and third trimesters between the < 30 years old group and ≥30 years old group ( P > 0.05). Comparison of abnormal rate of FT 4 in different gestational ages: there were no significant differences in the FT 4 abnormal rate among different pregnancy groups in the overall, < 30, ≥30 years old groups (P > 0.05). In early pregnancy, the abnormal rate of FT 4 in the ≥30 years old group was higher than that in the < 30 years old group ( P < 0.05); in second and third trimesters, there were no significant differences between the two age groups ( P > 0.05). Conclusions:Screening for thyroid function in the first trimester of pregnancy is important for women of different ages. Except for women with abnormal thyroid function who have not been treated during the first trimester, the rest may not need to be screened again. Pregnant women aged ≥30 years old may have a higher risk of thyroid dysfunction than those < 30 years old.

This work investigates the effects of Guilingji (GLJ) on D-galactose-induced aging and changes in serum metabolites by UHPLC-Q exactive orbitrap-MS in rats. The rat model of aging by subcutaneous injection of D-galactose (300 mg·kg^-1) was used to analyze the effect of different concentrations of GLJ (37.5, 75, 150 mg·kg^-1) on an open field test in aging rats. Rat serum was collected after 8 weeks and subjected to LC-MS to analyze the anti-aging effect of GLJ. Animal experimentation was approved according to the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2014032). GLJ significantly improved the autonomous activity of rats. Compared with the control group, 23 metabolites in the treated group changed significantly, involving three main pathways. The group that was given GLJ had altered regulation of 4 serum metabolites in two pathways. Our results indicate that GLJ can delay aging behavior in rats; the mechanism of this anti-ageing effect remains to be determined.