Postoperative cognitive dysfunction (POCD) is a clinically significant complication in elderly patients, largely driven by surgery-induced neuroinflammation. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, a crucial regulator of innate immunity, has been implicated in neuroinflammatory activation. This study investigated whether electroacupuncture (EA) improves POCD by modulating this pathway in aged rats. Aged male Sprague-Dawley rats were subjected to sevoflurane anesthesia and splenectomy to establish a POCD model. Animals were divided into sham, POCD, POCD+EA, and POCD+EA+cGAS inhibitor groups. The EA groups received stimulation at Baihui (Governor Vessel 20 (GV20)), Neiguan (Pericardium 6 (PC6)), and Zusanli (Stomach 36 (ST36)) acupoints. Cognitive function was evaluated using the Morris water maze, while hippocampal expression of cGAS-STING pathway components and downstream effectors—interferon regulatory factor 3 (IRF3), nuclear factor kappa B (NF-κB), and interleukin-1 beta (IL-1β)—was assessed by Western blot. Cellular localization was determined by immunofluorescence staining. Compared with the Sham group, rats in the POCD group showed significant impairments in spatial memory, accompanied by upregulated protein expression of cGAS, STING, NF-κB, IRF3, and IL-1β in the hippocampus. Upon pathway activation, cGAS and STING proteins were predominantly co-localized with neurons, and their fluorescence intensity in the hippocampus was markedly increased. These behavioral deficits and molecular alterations were partially reversed in both the POCD+EA and POCD+EA+inhibitor groups. Electroacupuncture alleviates POCD in aged rats by inhibiting hippocampal cGAS-STING pathway activation and reducing neuroinflammation, suggesting a promising non-pharmacological strategy for POCD management.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Objective : To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods : HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group. The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group. The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated. Results: Compared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins. At the same time , the levels of NRF2-related antioxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased. Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD.

Objective:To establish an HPLC characteristic chromatogram method to simultaneously determine the content of 6 components in Bombyx Batryticatus and its processed products; To provide a scientific means for quality evaluation.Methods:The HPLC analysis was performed on a Waters Xselect HSS T3 column (250 mm×4.6 mm, 5 μm), with a mobile phase consisting of acetonitrile and 5 mmol/L ammonium acetate solution (adjust pH to 4.5 with acetic acid) in gradient mode at a flow rate of 1.0 ml/min. The column temperature was 30 ℃. The detection wavelength was 260 nm. The injection volume was 10 μl. The SIMCA-P 14.0 software was used for cluster analysis and partial least squares discriminant analysis to evaluate the quality of Bombyx Batryticatus and its processed products.Results:Nine common peaks were identified in the HPLC characteristic spectra of Bombyx Batryticatus and its processed products, and seven common peaks were identified. Cluster analysis and partial least squares discriminant analysis can classify Bombyx Batryticatus and its processed products into two groups, with peak 4, peak 2, peak 1, peak 6, and peak 3 as their mass difference markers. Uric Acid, Hypoxanthine, Uridine, Adenine, Guanosine, and Adenosine showed good linearity ( R2≥0.999 9) within 43.95-879.04, 2.05-41.07, 2.35-47.09, 2.02-40.36, 2.32-46.43, 2.32-46.43 μg/ml, respectively. The precision, stability (24 h), repeatability relative standard deviation (RSD) were all <3.00%. The average spiked recoveries were all in the range of 94.57%-102.01%, and the RSDs were all in the range of 0.96%-3.32%. In 15 batches of Bombyx Batryticatus, the content of the above 6 components, was determined to be 11.51, 0.33, 0.38, 0.42, 0.35, 0.36 mg/g in the following order. And in 15 batches of fried Bombyx Batryticatus, the content of components was determined to be 12.06, 0.35, 0.36, 0.18, 0.21, 0.24 mg/g in the following order. Conclusions:The method established in this study is simple, rapid, and repeatable. PLS-DA can distinguish Bombyx Batryticatus and its processed products, which can provide a reference for the quality evaluation of Bombyx Batryticatus and its processed products.

Objective To determine the optimal extraction process for kaempferol from Alpinia officinarum Hance and to investigate its antioxidant activity.Methods Based on single-factor experimental data,this study employed the Box-Behnken central composite design and response surface methodology(RSM),combined with high-performance liquid chromatography(HPLC),to plot response surface and contour maps using kaempferol content as the response value.The optimal parameters for ethanol concentration,solid-liquid ratio,extraction time,and extraction temperature were selected.The antioxidant activity of kaempferol was comprehensively evaluated by calculating the radical scavenging rate using the DPPH radical scavenging assays.Results The optimal extraction conditions were determined to be an ethanol concentration of 84%,a solid-liquid ratio of 1∶80,an extraction time of 2 hours,and an extraction temperature of 82℃.Under these conditions,the kaempferol content extracted from Alpinia officinarum Hance reached 0.034 16%.In the DPPH radical scavenging assay,the extract showed a scavenging rate of 91.20%at a concentration of 1 mg/mL.Conclusion The optimized extraction process for kaempferol from Alpinia officinarum Hance was obtained using the Box-Behnken response surface design method,and this process is practical and feasible.The DPPH radical scavenging assay demonstrated that kaempferol from Alpinia officinarum Hance possesses antioxidant activity.

Objective To investigate the sequencing results of the SLC26A4 gene in 34 nuclear families and the genetic diagnosis on the offspring in the nuclear families who have been screened for SLC26A4 gene single-allele mutation in the deafness genetic screening,to provide a basis for genetic consulting.Methods A retrospective anal-ysis was performed on the results of SLC26A4 gene testing in 34 nuclear families,in which the offspring with SLC26A4 gene single-allele mutation in deafness genetic screening of each nuclear family.The offspring of 34 nucle-ar families with the second mutation site detected by sequencing,their audiological results were included in the anal-ysis;and if they suffered from hearing loss,the results of temporal bone CT or inner ear MRI were also included in the analysis.Results The sequencing results of 34 nuclear families showed that there were 23 offsprings(67.65％,23/34)with SLC26A4 gene single-allele mutation,and one parent was SLC26A4 gene single-allele mutation.There were 11 offsprings(32.35％,11/34)with second site,among which 7 offsprings(63.64％,7/11)with SLC26A4 gene complex heterozygous mutations,and their parents were SLC26A4 gene single-allele mutations.Among the 7 offsprings with SLC26A4 gene complex heterozygous mutation,3 cases were with hearing loss,all of which were diagnosed as large vestibular aqueduct syndrome,and the other 4 cases were normal.While 4 offsprings(36.36％,4/11)with SLC26A4 gene double heterozygous mutation(cis mutation),and one parent was SLC26A4 gene double heterozygous mutation.The hearing 4 offsprings with SLC26A4 gene double heterozygous mutations were normal.Among the 34 nuclear families,3 pairs of parents were SLC26A4 gene single-allele mutation,and both mutation sites were pathogenic,risk of reproducing children with hereditary hearing loss was 25％.Conclusion The detec-tion sites of deafness gene chip are limited.Using gene sequencing technology to sequence the nuclear family can fur-ther clarify the gene mutation type in offspring and provide guidance for parents to reproduce.

Objective:To investigate the current situation of professional identity and work readiness of newly graduated nursing students, explore the correlation between professional identity and work readiness, and provide a reference for promoting their professional development.Methods:From May to September 2023, a total of 584 newly graduated nursing students who were about to participate in standardized residency training were selected from 7 tertiary hospitals in the main urban area of Chongqing using cluster sampling. The general information questionnaire, Nurse Professional Identity Scale, and Nurse Work Readiness Scale were used for data collection. SPSS 23.0 was used to analyze the current situation of professional identity and work readiness among the participants.Results:A total of 536 valid questionnaires were collected, with an effective recovery rate of 91.78%. The professional identity scores of newly graduated nursing students ranged from 23 to 83 (66.94±11.38) points and the work readiness scores ranged from 115 to 370 (271.47±44.54) points, which were positively correlated ( r=0.673, P<0.001). Hierarchical regression analysis showed that professional identity entered into the influencing factor model of work readiness ( F=38.350, P<0.001), which could independently explain 50.80% of the variation in work readiness. Conclusions:The professional identity and work readiness of newly graduated nursing students are at moderate levels. Nursing educators and hospital nursing managers should pay attention to the assessment of their professional identity and work readiness, adopt scientific and effective methods to improve their work readiness, ensure a smooth professional transition, and promote their career development.

AIM:To investigate the potential mechanism of licorice on liver injury induced by Se-men Strychni based on network pharmacology,mo-lecular docking combined with animal experiments,providing an effective strategy for prevention and treatment of liver injury induced by Semen Strych-ni.METHODS:Firstly,the active ingredients of Se-men Strychni and licorice were obtained through the ETCM,TCMSP database and analysis platform,CTD database and literature supplementation.Then,the potential toxic ingredients of Semen Strychni were further screened based on the Swis-sADME platform,and the targets corresponding to the active ingredients were predicted through the SwissTargetPrediction platform.By using the Gene-Cards and OMIM databases to collect DILI-related targets,the potential targets for licorice to alleviate liver injury caused by Semen Strychni were ob-tained.By constructing the active ingredient-target network,the core ingredients of licorice in alleviat-ing liver injury caused by Semen Strychni were screened.The key targets obtained were used to construct and analyze the protein-protein interac-tion networks(PPI)through the STRING database and Cytoscape 3.9.0 software.The potential targets were subjected to GO and KEGG pathway enrich-ment analysis with the aid of the DAVID database,and constructed a network of active ingredient-tar-get-pathway.Molecular docking study was ap-proved for the core targets and the active ingredi-ents by using Schrodinger 2023-1 software,and the visualization operation was conducted through Py-mol.Finally,the regulatory effect of licorice on the key pathway of liver injury caused by Semen Strych-ni was validated by establishing a rat model of liver injury induced by Semen Strychni.RESULTS:After screening,6 potential toxic components of Semen Strychni and 104 corresponding targets,89 active components of licorice and 347 corresponding tar-gets,and 3 200 DILI targets were obtained.A total of 23 intersection targets were obtained through Venn analysis.By constructing the active ingredi-ent-target network,it was found that the main core ingredients were 7-methoxy-2-methyl isofla-vone,medicarpin,shinpterocarpin,quercetin,for-mononetin and isoliquiritigenin.The PPI network indicated that the core targets were protein kinase B1(AKT1),epidermal growth factor receptor(EG-FR),human epidermal growth factor receptor 2(ERBB2),glycogen synthase kinase 3 beta(GSK3B),kinase insert domain receptor(KDR)and Janus ki-nase 2(JAK2).A total of 39 relevant pathways were enriched in KEGG(P＜0.01),among which the phos-phatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)(PI3K-AKT)signaling pathway,which has been confirmed and ranks first in enrichment,and was closely related to liver injury.Molecular docking re-sults showed that the core components have good binding ability with the core targets.In vivo animal experiments demonstrated that,compared to the model group,licorice significantly reduced the liver index(P＜0.01),serum levels of alkaline phospha-tase(ALP),alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),indirect bilirubin(IBIL),and total bilirubin(TBIL)in rats with liver in-jury,while increasing total protein(TP)levels(P＜0.05 or P＜0.01).Additionally,licorice alleviated con-gestion in the central veins and hepatic sinusoids,improved the alignment of hepatocytes,and re-duced inflammatory cell infiltration.Furthermore,licorice significantly decreased the levels of malo-ndialdehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in the liver tissue of injured rats,while elevating the levels of superoxide dismutase(SOD)and glutathi-one peroxidase(GSH-Px)(P＜0.01).It also markedly downregulated the phosphorylation levels of PI3K and AKT(P＜0.01).CONCLUSION:Licorice has multi-component and multi-target properties in the treat-ment of liver injury induced by Semen Strychni,which may play a hepatoprotective role by inhibit-ing the activation of PI3K-AKT signaling pathway.