OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

OBJECTIVE To study the way in which hypidone hydrochloride(code:YL-0919)improves motor function after ischemic stroke(IS)and explore the related mechanism.METHODS Adult male SD rats were used to establish a middle cerebral artery occlusion(MCAO)model that simulated acute IS.All animals were randomly divided into four groups:sham group,MCAO group,MCAO+YL-0919 group,and MCAO+YL-0919+erastin(Era,ferroptosis inducer)group.The drug administration groups received the first ip injection 6 h after operation,followed by continuous ip injection once per day.After 7-10 d of drug administration,the effect of YL-0919 on motor function after IS were evaluated via neu-rological function test,adhesive-removal test,rotarod test,balance beam test and open field test.After 7 d of drug administration,TTC staining was used to detect the cerebral infarction area while the colo-rimetry method was used to measure the contents of glutathione(GSH),malondialdehyde(MDA),and ferrous ions(Fe2+)in the penumbra of the cerebral cortex.Western blotting was used to detect the expression levels of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(xCT),acyl-CoA synthetase long-chain family member 4(ACSL4),and transferrin receptor 1(TFR1)in the cortical penumbra.RESULTS Compared with the sham group,the MCAO group showed higher neurological function scores(P<0.01),with notably prolonged time for tape removal and first contact with the right forepaw(P<0.01),spent significantly more time crossing the balance beam(P<0.01)but endured a notably shorter duration on the rotarod(P<0.01),reduced the movement distance in the open field(P<0.01),had a remarkably increased infarct area(P<0.01)but significantly level of GSH in the cortical penumbra region decreased(P<0.01),while MDA and Fe2+levels were markedly increased(P<0.01).Protein expression levels of GPX4 and xCT were reduced(P<0.05),while those of ACSL4 and TFR1 were elevated(P<0.05).Compared with the MCAO group,these changes were significantly reversed after YL-0919 administration.However,when Era and YL-0919 were administered simultaneously,the reversal effect of YL-0919 was significantly weakened.CONCLUSION YL-0919 can improve motor function impairment and reduce cerebral infarction areas in rats after IS,and the mechanism may be related to the inhibition of ferroptosis.

Objective To investigate the expression of serum CC chemokine ligand 2(CCL2),CX3C chemokine ligand 1(CX3CL1)and CXC chemokine ligand 10(CXCL10)in postmenopausal osteoporosis(PMOP)patients and the value of combination with fracture risk assessment tool(FRAX)in predicting fracture occurrence.Methods A total of 120 patients with PMOP admitted to Hainan West Central Hospital from January 2022 to June 2023 were selected,and they were divided into fracture group(n=52)and non-fracture group(n=68).According to the FRAX score examination,they were divided into a high-risk fracture group(n=73)and a low-risk fracture group(n=47).The levels of serum CCL2,CX3CL1 and CXCL10 in each group were compared.Multivariate Logistic regression was used to analyze the fracture risk factors in PMOP patients.ROC curve was drawn to analyze the value of CCL2,CX3CL1 and CXCL10 combined with FRAX score in predicting fracture of PMOP.Results The levels of serum CCL2(134.98±32.24 pg/ml),CX3CL1(186.25±41.60 pg/ml)and CXCL10(223.47±56.43 pg/ml)in the fracture group were higher than those in the non-fracture group(82.26±17.30 pg/ml,105.23±23.78 pg/ml,151.47±43.14 pg/ml),and the differences were statistically significant(t=11.503,13.452,7.923,all P＜0.001).The levels of serum CCL2(119.70±37.56 pg/ml),CX3CL1(161.43±53.79 pg/ml)and CXCL10(204.06±61.41pg/ml)in the high-risk group for fractures were higher than those in the low-risk group(82.43±17.23 pg/ml,107.55±24.75 pg/ml,149.45±42.50pg/ml),and the differences were statistically significant(t=6.377,6.436,5.327,all P＜0.001).Multivariate Logistic regression analysis showed that elevated levels of serum CCL2,CX3CL1 and CXCL10 were risk factors for fractures in PMOP patients.The ROC curve showed that the combination of CCL2,CX3CL1 and CXCL10 combined with FRAX scores predicted the highest AUC(95％CI)for PMOP fractures[0.951(0.892～0.993)],with sensitivity and specificity of 98.2％and 85.6％,respectively.Conclusion The increased levels of serum CCL2,CX3CL1 and CXCL10 are risk factors for fracture in PMOP patients,and the combination with FRAX score has a good predictive value for fracture.

Objective:To investigate and compare the clinical effectiveness and efficacy of cannulated screws and suture anchors in assistance of locking plates reinforcement for enhancing fixation in the treatment of proximal humeral fractures.Methods:A retrospective analysis was conducted on the data of 121 patients with proximal humeral fractures who were treated by locking plates reinforcement at Hainan Western Central Hospital from January 2018 to January 2020.Based on the intraoperative method of auxiliary reinforcement for the greater tuberosity of humerus,the patients were divided into cannulated screw group(62 cases)and suture anchor group(59 cases).The Disabilities of the Arm,Shoulder and Hand(DASH)score,Constant-Murley Shoulder Score and Neer Shoulder Function(Neer)Score pre surgery,the 3rd month and 12th month after surgery were recorded and compared between the two groups,so as to assess the changes in shoulder function.Results:The time of operation,the intraoperative bleeding volume,the length of stay and the follow up time of cannulated screw group were respectively(94.7±13.4)min,(230.5±39.2)ml,(9.2±1.3)d and(15.3±4.2)months,and the differences of them between two groups were no significant(P>0.05).All patients were satisfactory for the postoperatively proximal humeral fractures and the reduction of greater tuberosity,and there was no acromial impingement.The DASH scores of two groups at the 12th month after surgery were lower than those at the 3rd month after surgery,and the Constant-Murley scores and Neer scores of two groups at the 12th month after surgery were higher than those at the 3rd month after surgery,and the differences of them were significant(t=12.069,11.446,15.553,14.879,16.223,18.209,P<0.05),respectively.There were no statistically significant differences in DASH score,Constant-Murley score and Neer score at 3rd month and 12th month after surgery between the two groups(P>0.05).Conclusion:During surgical treatment for proximal humeral fractures,both cannulated screws and suture anchors can effectively assist to lock plate for strengthening fixation of the greater tuberosity,and maintaining anatomical reduction of the greater tuberosity,and promoting recovery of the function of shoulder joint.

Objective:To investigate the diagnostic value of serum CircRNA_0048211 expression level in postmenopausal osteoporosis (PMOP) and its correlation with bone-specific alkaline phosphatase (BALP), osteopontin (OPN), procollagen type I N-terminal propeptide (PINP) and β-crosslaps (β-CTX). Methods:Data of postmenopausal women who underwent physical examination in our hospital from January 2019 to December 2021 were collected. All subjects were measured bone mineral density (BMD) by dual-energy X-ray absorptiometry and divided into PMOP group, decreased bone mass group and normal bone mass group according to BMD level. The serum CircRNA_0048211, BALP, OPN, PINP and β-CTX levels were compared in each group. Binary logistic regression was used to analyze the risk factors of PMOP, the receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of CircRNA_0048211, BALP, OPN, PINP and β-CTX on PMOP. The correlation between CircRNA_0048211 expression level and BALP, OPN, PINP and β-CTX was analyzed by Pearson correlation analysis. Results:A total of 218 patients were included in this study. Age is 60.52±6.83 years (range, 47-76 years), body mass index is 24.27±2.28 kg/m 2 (range, 22.18-25.73 kg/m 2) and menopausal time is 10.16±4.25 years (range, 2.30-21.80 years). There were 40 cases in PMOP group, 97 cases in osteopenia group and 81 cases in normal bone mass group. The serum CircRNA_ 0048211, BALP, OPN, PINP and β-CTX was significantly different between PMOP group, osteopenia group and normal group ( F=21.15, P<0.001; F=12.52, P<0.001; F=17.86, P<0.001; F=14.32, P<0.001; F=15.52, P<0.001). The serum CircRNA_0048211 level in PMOP group (0.37±0.08) were significantly lower than that of osteopenia group (1.05±0.46) and normal bone mass group (1.73±0.81), the difference was statistically significant ( P<0.05). The levels of BALP (28.42±7.35 μg/L), OPN (17.28±7.30 ng/ml), PINP (58.40±14.37 ng/ml) and β-CTX (1.52±0.28 μg/L) in PMOP group were significantly higher than those in osteopenia group (22.61±5.93 μg/L, 11.95±5.64 ng/ml, 49.16±11.24 ng/ml, 0.81±0.17 μg/L) and normal bone mass group (16.30±4.18 μg/L, 7.62±3.25 ng/ml, 35.48±7.12 ng/ml, 0.37±0.10 μg/L), the difference was statistically significant ( P<0.05). Binary logistic regression analysis showed that decreased CircRNA_0048211 expression level [ OR=3.53, 95% CI (2.73, 10.32)] was a risk factor for the occurrence of PMOP ( P<0.001). ROC curve showed that CircRNA_0048211≤0.76 has a diagnostic significance on PMOP, and its combination of BALP, OPN, PINP and β-CTX has the highest AUC [0.95, 95% CI (0.89, 1.00)] in diagnosing PMOP. Correlation analysis showed that CircRNA_0048211 expression level were negatively correlated with BALP, OPN, PINP and β-CTX ( r=-0.46, P<0.001; r=-0.80, P<0.001; r=-0.81, P<0.001; r=-0.69, P<0.001). Conclusion:The CircRNA_0048211 showed low expression in PMOP, which was negatively correlated with BALP, OPN, PINP and β-CTX. The combination of these five factors has certain clinical value in the diagnosis of PMOP.

Anti-contactin associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis with variable clinical symptoms and atypical imaging manifestations. The prognosis of the patients with severe disease is poor. Reversible posterior leukoencephalopathy syndrome is rarely reported in autoimmune encephalitis. The clinical data, diagnosis and treatment of a patient with anti-CASPR2 antibody encephalitis complicated with reversible posterior encephalopathy syndrome were reported, in order to improve the understanding of clinicians on the rare disease complicated with atypical imaging manifestations.

In recent years, selenium nanoparticles (SeNPs) have been widely used in many fields such as nanotechnology, biomedicine and environmental remediation due to their good electrical conductivity, photothermal properties and anticancer properties. In this study, the cell-free supernatant, whole cell and the cell-free extracts of the strain Cupriavidus sp. SHE were used to synthesize SeNPs, and several methods were applied to analyze the crystal structure and surface functional groups of the nanoparticles. Finally, Pseudomonas sp. PI1 (G⁺) and Escherichia coli BL21 (G⁻) were selected to investigate the antibacterial properties of SeNPs. Cell-free supernatant, whole cell and cell-free extracts of the strain could synthesize SeNPs. As for the cell-free supernatant, selenite concentration of 5 mmol/L and pH=7 were favorable for the synthesis of SeNPs. TEM images show that the average size of nanospheres synthesized by the supernatant was 196 nm. XRD analysis indicates the hexagonal crystals structure of SeNPs. FTIR and SDS-PAGE confirmed the proteins bound to the surfaces of SeNPs. SeNPs synthesized by cell-free supernatant showed no antimicrobial activities against Pseudomonas sp. PI1 and Escherichia coli BL21 (DE3). These results suggest that proteins played an important role in biotransformation of SeNPs in an eco-friendly process, and SeNPs synthesized in this study were non-toxic and biologically compatible, which might be applied in other fields in the future.
Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; Cupriavidus ; metabolism ; Nanoparticles ; Selenious Acid ; analysis ; Selenium ; chemistry ; pharmacology

OBJECTIVE To investigate the effect of overexpession of 18 ku translocator protein (TSPO) on the hippocampal dentate gyrus. METHODS Lentiviral (LV) vectors containing TSPO or the lentiviral sequence were infused into the hippocampus bilateral dentate gyri (2 × 108 TU · mL-1,1 μL per side)of mice. Behavioral tests were carried out. The anxiolytic-like behavior of mice was examined by such means as the elevated plus maze test , the staircase test , light dark box test for 12, 14 and 16 d, two behavioral despair models, tail suspension test and the forced swimming test for 16 and 18 d,respec?tively. Western blotting and ELISA were used to evaluate the TSPO expression and the concentration of allopregnanolone in hippocampal tissue (3 mm in diameter around the injection site on both sides) at the end of tests. RESULTS The results of behavioral experiments showed that TSPO overexpression group deneloped anxiolytic and antidepression-like behavior. LV-TSPO significantly increased the retention time in the central area〔14 ± 4 vs (25 ± 12)s,P<0.05〕. LV-TSPO significantly increased the percentage of entry into open arms entries percentage and the percentage of time spent in open arms time without changing total entries and total time in the elevated plus-maze test〔(13±8)%vs (26±18)%, P<0.05;(6 ± 6)%vs (27 ± 6)%, P<0.05)〕. LV-TSPO significantly decreased the number of rearings without changing the number of steps in staircase test (21±7 vs 12±5,P<0.05). LV-TSPO increased entries into the light area and retention time in light-dark transition test〔(18 ± 8)% vs (26 ± 7)%, P<0.05;72 ± 36 vs (191 ± 90)s, P<0.05)〕but significantly decreased immobility time in the tail suspension test and forced swimming test〔94±33 vs (36±20)s, P<0.01;137±36 vs (90±37)s, P<0.05)〕, without excitatory or inhibitory actions on the central nervous system. At the same time, the level of TSPO expression in hippocampal tissues (3 mm in diameter around the injection site on both sides) was significantly increased, so did the concentration of allopregnanolone (P<0.05). CONCLUSION Overexpression of TSPO in the hippocamus dentate gyrus of mice can induce anxiolytic and antidepressant-like behavior, and the downstream allo?pregnanolone biosynthesis at least partially mediates the behavioral effects.

OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.

OBJECTIVE To investigate the relationship between the anti-post-traumatic stress disorder(PTSD)effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline(15 mg · kg-1) intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and 7th day after the extinction training in rats. The NO contents were detected by Griess method and the nNOS and iNOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group ,the freezing time was significantly increased in extinction control group and extinction training group(P<0.01),indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline(15 mg·kg-1)group was decreased compared with extinction training group (P<0.05). At the 7th day,the freezing time was significantly decreased(P<0.01),indicating that ser?traline reversed the fear response. At the same time,the contents of NO,nNOS and iNOS on amygdala of rats in sertraline group were lower than that in extinction training group(P<0.01). CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has anti-PTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.