Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model's robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model's ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.
Animals ; Machine Learning ; Electroencephalography/methods* ; Ketamine/administration & dosage* ; Rats ; Male ; Propofol/administration & dosage* ; Rats, Sprague-Dawley ; Anesthesia, General/methods* ; Brain/physiology* ; Intraoperative Neurophysiological Monitoring/methods*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective To compare the value of high-field strength MRI half-Fourier single shot turbo spin-echo(HASTE)sequence with high-frequency color Doppler ultrasound for the diagnosis of placenta previa combined with placenta accreta.Methods A total of 116 pregnant women with suspected high-risk placenta previa and placenta accreta who underwent cesarean section at The No.2 Hospital of Baoding from December 2019 to December 2022 were selected as research objects.All parturients took examinations of ultrasound and high-field MRI before surgery.Pathological diagnosis after cesarean section was used as the gold standard for analysis of the consistency between MRI and ultrasound results and pathological results.The value of HASTE sequence and high-frequency ultrasound in diagnosing placenta accreta was compared.Results Pathological results confirmed that 86 patients had high-risk placenta previa and placenta accreta.The positive predictive values of ultrasound,MRI,and ultrasound+MRI in diagnosis of high-risk placenta previa combined with placenta accreta were 93.51%,97.62%,and 98.81%,respectively.The negative predictive values were 64.10%,87.50%,and 90.63%,respectively.The accuracies were 83.62%,94.83%,and 96.55%,respectively.The sensitivities were 83.72%,95.35%,and 96.51%,respectively.The specificities were 83.33%,93.33%,and 96.67%,respectively.The Kappa values for consistency were 0.611,0.868,and 0.912,respectively.The accuracy of MRI in diagnosis of high-risk placenta previa combined with placenta accreta was higher than that of ultrasound(P<0.05).Conclusion 3.0 T MRI HASTE sequence has greater efficacy and higher accuracy in diagnosis of high-risk placenta previa combined with placenta accreta.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.

AIM:To study the effect of Sanhuang Gel on the expression of TLRs/NLRP3 signal path-way in auricle acne model rats,and to explore its mechanism in treating acne inflammatory injury.METHODS:A rat model of auricular acne was in-duced by applying 100％oleic acid to the opening of the right ear catheter and injecting Propionibac-terium acnes.Rats were divided into normal group,model group,positive control group(clindamycin hydrochloride gel 10 mg/g)and Sanhuang Gel high,medium and low dose groups(280,140 and 70 mg/g).Each drug group was given drug intervention for 28 days.The changes of auricle skin lesions in each group were observed;Hematoxylin-eosin(HE)staining was used to observe the pathological changes of auricle acne.The ultrastructural chang-es of auricle tissue cells were observed by transmis-sion electron microscope(TEM).The distribution and expression changes of TLR2 and TLR4 in rat au-ricle tissue were detected by immunofluorescence.The expressions of TLR2,TLR4,NLRP3,ASC and Cas-pase-1 mRNA in rat auricle were detected by Real-time PCR.The expressions of TLR2,TLR4,NLRP3,ASC and Caspase-1 in rat auricle were detected by Western blot.RESULTS:Compared with the normal group,papules,pustules,inflammatory cell infiltra-tion and obvious edema of mitochondria can be seen in the auricle tissue of the model group.The mRNA and protein expression levels of TLR2,TLR4,NLRP3,ASC andCaspase-1 increased significantly(P＜0.01).Compared with the model group,the ap-pearance and pathological damage of auricle in each treatment group were obviously alleviated,and the morphology and structure of mitochondria returned to normal.The mRNA expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 decreased significantly(P＜0.01).The expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 in positive control group and high and middle dose groups de-creased(P＜0.01,P＜0.05).The expression levels of ASC and Caspase-1 protein in low dose group were significantly decreased(P＜0.01),but there was no significant difference in the expression levels of TLR2,TLR4 and NLRP3 protein(P＞0.05).CONCLU-SION:Sanhuang Gel can improve the pathological damage of auricle tissue and reduce immune in-flammatory reaction in acne rats,and its mecha-nism may be related to regulating TLRs/NLRP3 sig-naling pathway.

AIM:To study the effect of Sanhuang Gel on the expression of TLRs/NLRP3 signal path-way in auricle acne model rats,and to explore its mechanism in treating acne inflammatory injury.METHODS:A rat model of auricular acne was in-duced by applying 100％oleic acid to the opening of the right ear catheter and injecting Propionibac-terium acnes.Rats were divided into normal group,model group,positive control group(clindamycin hydrochloride gel 10 mg/g)and Sanhuang Gel high,medium and low dose groups(280,140 and 70 mg/g).Each drug group was given drug intervention for 28 days.The changes of auricle skin lesions in each group were observed;Hematoxylin-eosin(HE)staining was used to observe the pathological changes of auricle acne.The ultrastructural chang-es of auricle tissue cells were observed by transmis-sion electron microscope(TEM).The distribution and expression changes of TLR2 and TLR4 in rat au-ricle tissue were detected by immunofluorescence.The expressions of TLR2,TLR4,NLRP3,ASC and Cas-pase-1 mRNA in rat auricle were detected by Real-time PCR.The expressions of TLR2,TLR4,NLRP3,ASC and Caspase-1 in rat auricle were detected by Western blot.RESULTS:Compared with the normal group,papules,pustules,inflammatory cell infiltra-tion and obvious edema of mitochondria can be seen in the auricle tissue of the model group.The mRNA and protein expression levels of TLR2,TLR4,NLRP3,ASC andCaspase-1 increased significantly(P＜0.01).Compared with the model group,the ap-pearance and pathological damage of auricle in each treatment group were obviously alleviated,and the morphology and structure of mitochondria returned to normal.The mRNA expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 decreased significantly(P＜0.01).The expression levels of TLR2,TLR4,NLRP3,ASC and Caspase-1 in positive control group and high and middle dose groups de-creased(P＜0.01,P＜0.05).The expression levels of ASC and Caspase-1 protein in low dose group were significantly decreased(P＜0.01),but there was no significant difference in the expression levels of TLR2,TLR4 and NLRP3 protein(P＞0.05).CONCLU-SION:Sanhuang Gel can improve the pathological damage of auricle tissue and reduce immune in-flammatory reaction in acne rats,and its mecha-nism may be related to regulating TLRs/NLRP3 sig-naling pathway.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

OBJECTIVE To observe the anti-inflammatory mechanism of Sanhuang gel on rat model of auricle acne and its possible mechanism with p38MAPK signaling pathway as the entry point. METHODS Sixty-two male Wistar rats were divided into blank group and modelling group. The modeling group replicated the experimental animal model of acne(application of 100% oleic acid+subcutaneous injection of Propionibacterium acnes), and 2 rats were randomly selected for HE staining after 21 days. The remaining rats were randomly divided into model group, positive control group(Vitamin A cream 1.48 g·d−1 ), Sanhuang gel high, medium and low-dose group(1.1, 0.568, 0.3 g·d−1 ). They were administered for 8 weeks, and observed on the 7, 14 and 28 day of treatment. The right auricle tissues were collected, and the histopathological changes were observed by HE stain. The mRNA expressions of p38MAPK, MKK3 and MKK6 were detected by RT-PCR. The protein expressions of MCP-1, HMGB1 and α-SMA in auricle tissues were detected by IHC and Western blotting. RESULTS Compared with blank group, the epidermis of auricular tissue in model group was severely keratinized, inflammatory cell infiltration was obvious, mRNA levels of p38MAPK, MKK3, MKK6 and protein expression levels of MCP-1, HMGB1 and α-SMA were increased(P<0.05). After drug therapy intervention, auricle apparent score at different time points in each treatment group was improved to varying degrees. The mRNA levels of p38MAPK, MKK3, MKK6 and protein levels of MCP-1, HMGB1 and α-SMA in Sanhuang gel high-dose and medium-dose groups and positive control group were decreased(P<0.05), while in Sanhuang gel low-dose group, the expressions of MKK3 mRNA and MCP-1, HMGB1 protein were decreased(P<0.05), the expression of p38MAPK, MKK6 mRNA and α-SMA protein decreased not significantly. CONCLUSION The mechanism of the effect of Sanhuang gel on the inflammatory response of rat compound acne animal model may be related to its intervention of p38MAPK protein feedback regulation signaling pathway and inhibition of MCP-1, HMGB1 and α-SMA expression.

Objective:To investigate the relationship between the cerebral small vascular disease (CSVD) total burden and the imaging markers and the degree of unilateral middle cerebral artery (MCA) stenosis.Methods:The study was a cross-sectional study. Clinical and imaging data of patients with chronic unilateral MCA stenosis who underwent multimodal MRI from October 2015 to January 2019 in the First Medical Center of PLA General Hospital were retrospectively analyzed. A total of 261 patients were included, 187 males and 74 females. According to the degree of MCA stenosis, the patients were divided into 102 cases in severe stenosis-occlusion group (stenosis degree ≥70%) and 159 cases in mild-moderate stenosis group (stenosis degree <70%). CSVD imaging marker scores (including white matter hyperintensity, perivascular space, cerebral microbleed, and lacune of presumed vascular origin) were assessed according to the ?standards for reporting vascular changes on neuroimaging 1 in the 2 groups, and the CSVD total burden score was calculated. Mann-Whitney U test was used to compare the indicators between the two groups, and the CSVD total burden score and imaging marker scores were ultimately included in a multifactorial binary logistic regression to assess the association of CSVD imaging markers with severe stenosis-occlusion of the MCA after adjusting for vascular risk factors (age, gender, drinking, smoking, hypertension, hyperlipidemia, atrial fibrillation and coronary heart disease). Results:There were significant differences in the CSVD total burden, centrum semiovale perivascular space and lacune of presumed vascular origin score between the mild-to-moderate stenosis group and the severe stenosis-occlusion group (all P<0.05), and none of the differences in the remaining imaging marker scores were statistically significant (all P>0.05). Multivariate binary logistics regression analysis showed CSVD total burden score ( OR=1.300, 95% CI 1.047-1.613, P=0.017), centrum semiovale perivascular space score ( OR=2.099, 95% CI 1.540-2.860, P<0.001) and lacune of presumed vascular origin score ( OR=2.609, 95% CI 1.294-5.261, P=0.007) were independent associated with severe stenosis-occlusion of MCA. Conclusion:The higher CSVD total burden score, centrum semiovale perivascular space score and lacune of presumed vascular origin score are associated with severe stenosis-occlusion of MCA.