ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Attention is the cornerstone of effective functioning in a complex and information-rich world. While the neural activity of attention has been extensively studied in the cortex, the brain-wide neural activity patterns are largely unknown. In this study, we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns. Our findings reveal that a wide range of brain regions are activated, notably in the high-order cortex, thalamus, and brain stem regions involved in advanced cognition and arousal regulation, with the central lateral nucleus of the thalamus as a strong hub, suggesting the crucial role of the thalamus in attention control. These results provide valuable insights into the neural network mechanisms underlying attention, offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
Animals ; Attention/physiology* ; Mice ; Brain/physiology* ; Male ; Electroencephalography ; Reaction Time/physiology* ; Brain Mapping ; Mice, Inbred C57BL ; Choice Behavior/physiology* ; Proto-Oncogene Proteins c-fos/metabolism*

Objective To investigate the changes of C1q tumor necrosis factor-related protein-12(CTRP12)levels in serum of the pa-tients with acute myocardial infarction(AMI)before and after percutaneous coronary intervention(PCI),and explore its clinical sig-nificance.Methods A total of 50 patients with AMI who underwent emergency PCI and 35 patients with normal coronary angiography results in Danyang People's Hospital from November 2021 to October 2022 were enrolled.The CTRP12 levels in peripheral venous ser-um were compared between the two groups.The levels of serum CTRP12 levels were measured before,during and on the 3rd,5th and 7th day after PCI.The serum CTRP12 levels in culprit coronary ostium and peripheral vein were compared.CTRP12 levels in peripher-al venous serum were compared at different time points after PCI.The severity of coronary artery disease was evaluated by SYNTAX score system,and the AMI patients were divided into two groups:SYNTAX score ≤22 and SYNTAX score＞22.The serum CTRP12 levels were compared between the two groups and before and after PCI.The correlation between CTRP12 and age,body mass index(BMI),fasting blood glucose,blood lipid and other factors was analyzed.The influencing factors of the severity of coronary artery le-sions were analyzed by logistic regression.Results The serum CTRP12 level in the patients with AMI was significantly lower than that in healthy controls(P＜0.05).There was no significant difference between the serum CTRP12 levels between preoperative peripheral vein and intraoperative culprit coronary orifice(P＞0.05).Compared with that before PCI,the serum CTRP12 level was lower on the 3rd day after PCI(P＜0.05),and increased on the 5th and 7th days after PCI,but no statistically significant difference was found(P＞0.05).Compared with those on the 3rd day after PCI,the serum CTRP12 levels were increased on the 5th and 7th day after PCI,but no statistically significant differences were found(all P＞0.05).Compared with that in the SYNTAX≤22 group,the CTRP12 levels were significantly lower than those before PCI and on the 3rd day after PCI(all P＜0.05),while there was no significant difference on the 5th and 7th day after PCI in SYNTAX＞22 group(all P＞0.05).CTRP12 was negatively correlated with the level of total cholesterol(TC)and positively correlated with high-density lipoprotein cholesterol(HDL-C).Univariate logistic regression analysis showed that CTRP12 was an independent influencing factor for the severity of coronary artery disease in the patients with AMI(β=-1.671,OR=0.188,P＜0.05).After adjusting for the effects of age,gender,BMI,smoking,hypertension,diabetes,fasting blood glucose,total cholesterol(TC),triglyceride(TG),HDL-C and low-density lipoprotein cholesterol(LDL-C),CTRP12 was still an independent in-fluencing factor for the severity of coronary artery disease in the patients with AMI(β=-3.441,OR=0.032,P＜0.05).Conclusion The serum CTRP12 level was significantly decreased in the patients with AMI before PCI,and showed continuous decline on the 3rd day after PCI,but increased on the 5th and 7th day after PCI.CTRP12 should be an independent influencing factor for the severity of coronary artery disease in the patients with AMI.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

OBJECTIVE To systematically evaluate the efficacy and safety of the sedative effect of remimazolam in endoscopy and to compare it with propofol and midazolam. METHODS Search PubMed, Embase, Cochrane Library, Wanfang database, CNKI and other databases to collect the literature of randomized controlled trials of remimazolam for sedation in endoscopy. The search period was from 2018 onwards when remimazolam was approved for clinical trials until April 2022. The search strategy included the following variable keywords: remimazolam, gastroscopy, bronchoscopy, and colonoscopy. The quality of the included literature was assessed and the collected data were subjected to meta-analysis by RevMan 5.4 software. RESULTS Ten relevant RCTs involving midazolam and propofol, involving a total of 2 076 patients were included in the analysis. The results showed that the sedative effect of remimazolam was significantly higher than that of midazolam [OR=0.03, 95%CI(0.02, 0.05), I2=0%, P<0.000 01]; but lower than that of propofol [OR=11.32, 95%CI(2.12, 60.56), I2=0%, P=0.005]. The onset time of remimazolam was longer than that of propofol, but shorter than that of midazolam; the recovery time was faster than that of propofol and midazolam. Compared with midazolam, there was no significant difference in the incidence of adverse reactions. Compared with propofol, remimazolam was associated with lower rates of hypotension, slowed heart rate, hypoxemia, and injection pain, but higher risk ratio of nausea, with no difference invomiting. CONCLUSION The sedative effect and onset of action of remimazolam are better than midazolam but less than propofol when used for endoscopy. Wake-up time is faster than that of propofol and midazolam. The incidence of respiratory and circulatory depression is lower with remimazolam than with propofol, and there are no significant differences in adverse effects compared with midazolam.

Objective This study examined the influence of c-Myc regulated long noncoding RNA TBL1XR1-5(lnc-TBL1XR1-5)on the progression of oral squamous cell carcinoma(OSCC).Methods Based on the expres-sion of c-Myc,bioinformatics analysis was performed on head and neck squamous cell carcinoma samples in the TCGA database,and lnc-TBL1XR1-5 with closely related c-Myc expression was screened.The effects of c-Myc overexpression and knockdown on lnc-TBL1XR1-5 were detected.Expression relationship of c-Myc and lnc-TBL1XR1-5 in OSCC and para-cancer tissues.Dual-luciferase reporter assays were used to verify the binding of c-Myc to the lnc-TBL1XR1-5 promoter region.RNA FISH were used to determine the localization of lnc-TBL1XR1-5 in OSCC cell lines.The effects of overexpression,knockdown of lnc-TBL1XR1-5 on migration,metabolism,and proliferation of OSCC cells were observed by quantitative real-time polymerase chain reaction(qRT-PCR),scratch tests,transwell assays,medium color and pH changes,cell counts,CCK-8 assay,and colony formation assays.Results It was found that c-Myc positively regulated the expression of lnc-TBL1XR1-5 in OSCC cell lines and tis-sues.The binding of c-Myc to the lnc-TBL1XR1-5 promoter region was verified by dual-luciferase reporter assays.RNA FISH showed that lnc-TBL1XR1-5 was localized in the nuclei in OSCC cells.Overexpression of lnc-TBL1XR1-5 promoted migration,metabolism and proliferation in OSCC cell lines,while knockdown of it had the opposite effect.Conclusion c-Myc positively regulates lnc-TBL1XR1-5 in OSCC.Lnc-TBL1XR1-5 affect the mi-gration,proliferation,and metabolism of OSCC by influencing the tumor microenvironment.

Objective To explore the action mechanism of long non-coding RNA(lncRNAs)lncRNA KCTD13-DT in oral squamous cell carcinoma(OSCC)and its potential interaction with transcription factor c-Myc,providing a potential diagnostic and therapeutic target for patients with OSCC.Methods The expression of lncRNA KCTD13-DT in OSCC and paracancerous tissues was detected by qRT-PCR.The effects of c-Myc overexpression and knock-down on human tongue squamous carcinoma cells HN6 and CAL27 were detected by qRT-PCR.Fluorescence in si-tu hybridization(FISH)assessed the localization of lncRNA KCTD13-DT in cells.A dual luciferase reporter gene was used to analyze the role of c-Myc in target binding to the promoter region of lncRNA KCTD13-DT.Stable cell lines with knockdown or overexpression of lncRNA KCTD13-DT were constructed in human OSCC cell lines HN6 and CAL27 by lentiviral infection,and the knockdown and overexpression efficiencies of lncRNA KCTD13-DT were detected by qRT-PCR.Cell proliferation changes were detected by growth curve assay,CCK-8 assay,colony forma-tion assay,and cell migration was detected by scratch assay and Transwell.Results lncRNA KCTD13-DT expres-sion level was reduced in OSCC tissues and OSCC cells(HN6,CAL27),and Western blot verified that after knoc-king down and overexpression of c-Myc in HN6 and CAL27,the qRT-PCR experiments showed that c-Myc nega-tively regulated lncRNA KCTD13-DT,and overexpression of c-Myc significantly down-regulated lncRNA KCTD13-DT;knockdown of c-Myc significantly up-regulated lncRNA KCTD13-DT levels.Dual luciferase reporter gene showed that c-Myc could target lncRNA KCTD13-DT,and c-Myc could be involved in regulating and repressing the transcriptional activity of lncRNA KCTD13-DT.FISH showed that lncRNA KCTD13-DT mainly existed in the nu-cleus.Growth curve assay,CCK-8 assay,cell scratch assay,Transwell,and colony formation assay showed that knockdown of lncRNA KCTD13-DT promoted the growth and proliferation of OSCC cells,and overexpression of ln-cRNA KCTD13-DT significantly inhibited the proliferation and migration of OSCC cells.Conclusion lncRNA KCTD13-DT is negatively regulated by c-Myc.Knockdown of lncRNA KCTD13-DT promotes cell proliferation,while overexpression of it inhibits cell growth.

Cuproptosis is a new type of cell death that depends on intracellular copper accumulation to trigger the aggregation of mitochondrial lipoacylated protein and the degradation of iron-sulfur cluster protein,with a different mechanism of action from autophagy,ferroptosis,pyroptosis,and necroptosis.Cuproptosis is closely association with the development of liver cancer and resistance to antitumor drugs,as well as the progression of various liver diseases such as hereditary liver diseases,nonalcoholic fatty liver disease,viral hepatitis,and liver cirrhosis.This article summarizes the mechanism of cuproptosis and its role in liver diseases,in order to provide a reference for further research and treatment of liver diseases.

Objective To compare the advantages of robot assisted and DSA guided PBC for the treatment of trigeminal neuralgia.Methods A retrospective clinical analysis was conducted on 85 patients(28 in robot group and 57 in DSA group)who underwent robot assisted and DSA guided PBC surgery in a same center from September 2021 to February 2024.The single puncture success rate,improvement rate of VAS score,clinical efficacy rate,incidence of complications,average surgical time and fluoroscopy time were compared between the two groups.Results There was no statistically significant difference between the two groups in terms of single puncture success rate(96.43% vs.84.21% ),VAS improvement rate[88.9% (77.78%,100.00% )vs.88.89% (55.56%,100.00% )],clinical effective rate(92.86% vs.94.74% ),and total incidence of complications(35.09% vs.42.11% )(P>0.05).The average surgical time was significantly higher in the robot group[38.50(35.00,48.00)min]than the DSA group[19.00(15.00,25.50)min],and the average fluoroscopy time in the robot group[13.00(12.00,15.75)s]was significantly lower than the DSA group[194.00(152.50,259.50)s].The difference in average surgical and fluoroscopy time between the two groups was statistically significant(P<0.05).Conclusion DSA guided surgery has more advantages in centers with a large number of patients and a pursuit of efficiency.The robot assisted surgical puncture process is safe and controllable and patient radiation exposure time is short,thereby having high clinical application and promotion value.