The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Objective:To investigate the application value of scenario simulation combined with standardized patient teaching in the training of doctor-patient communication skills among interns.Methods:A total of 110 clinical medicine interns were selected from Qilu Hospital of Shandong University and were divided into experimental group and control group using a random number table, with 55 interns in each group. The interns in the control group received traditional lecturing, and those in the experimental group received scenario simulation combined with standardized patient case-based teaching. The SEGUE Communication Skill Evaluation Scale and Patient Satisfaction Questionnaire were used to assess the improvement in communication skills in both groups, and Physician Self-Evaluation Scale and Course Satisfaction Questionnaire were used to assess the effectiveness of the course and the degree of satisfaction with the course. SPSS 26.0 was used for the t-test, the Mann-Whitney U test, and the rank sum test. Results:After training, both groups showed significant improvements in communication skills and patient satisfaction [experimental group in terms of communication skills: (55.38±13.11) vs. (74.82±6.75), P<0.001; experimental group in terms of patient satisfaction: 39.00 (39.00, 42.00) vs. 81.00 (79.00, 83.00), P<0.01; control group in terms of communication skills: (56.53±12.34) vs. (65.45±10.18), P<0.001; control group in terms of patient satisfaction: 39.00 (39.00, 42.00) vs. 73.00 (68.00, 77.00), P<0.001], and the experimental group had significantly higher scores than the control group [communication skills: (74.82±6.75) vs. (65.45±10.18), P<0.001; patient satisfaction: 81.00 (79.00, 83.00) vs. 73.00 (68.00, 77.00), P<0.001]. The Physician Self-Evaluation Scale showed that the experimental group had a significant improvement compared with the control group ( P<0.05). The results of the Course Satisfaction Questionnaire showed that the degree of overall satisfaction of the course was only 87.28% in the control group, while all the interns in the experimental group were satisfied with the course ( P<0.001); the new teaching method showed great advantages ( P<0.001). Conclusions:In the training of doctor-patient communication skills among interns, the application of scenario simulation combined with standardized patient case-based teaching can significantly improve their abilities of the application of knowledge application, humanistic concern, and communication skills, and therefore, it is an effective and promising method for the training of doctor-patient communication skills.

Objective To observe the ultrasonic manifestations of aggressive angiomyxoma(AAM).Methods Four patients with newly diagnosed AAM and 3 with recurrent AAM confirmed by pathology were retrospectively enrolled,and the ultrasonic manifestations were analyzed.Results Among 7 cases of AAM,the lesions located in subcutaneous regions of perineum in 3 cases,in both perineum and pelvic cavity in 2 cases,in pelvic cavity and in cervix each 1 case,with a median maximum diameter of 7.6 cm.The lesions mainly manifested as heterogeneous hypoechoic,scattered cord-like moderate/moderate-hyperechoic inside,regular or lobulated shape with finger-like protrusions,with clear boundary or unclear boundary with adjacent vagina/rectum.Layered structure could be observed with gray-scale ultrasound and CDFI.Conclusion AAM mainly affected pelvis and perineal region,often manifested as large lesion tended to infiltrate surrounding areas and form finger-like protrusions,most with clear boundaries and interior heterogeneous hypoechoic regions,also the characteristic stratified structures.

Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

Objective Jiedu Tongluo Tiaogan Formula(JTTF)is an effective formula for the clinical treatment of type 2 diabetes mellitus(T2DM).We used integrated pharmacology and in vitro experiments to explore the molecular mechanism of JTTF to improve insulin resistance(IR)in T2DM.Methods The drug targets of JTTF were obtained by identifying the key active ingredients of JTTF through UPLC-Q-TOF-MS.Multiple databases such as GeneCards,OMIM,and DrugBank were used to screen T2DM-IR related targets.Cytoscape software and String 11.0 database were used to construct the PPI network diagram of JTTF for T2DM-IR.GO and KEGG analyses were performed according to the Metascape platform to find the biological pathways related to the target proteins.AutoDock Tools software was used to simulate molecular docking.In vitro experiments were performed using palmitic acid(PA)-induced HepG2-IR cell model to detect the effect of JTTF on HepG2-IR.Results 28 effective active components of JTTF were screened.There were 857 gene targets of T2DM-IR,and 168 targets of drug-disease intersection.387 GO entries and 145 KEGG pathways were enriched.The molecular docking results showed that the main components of JTTF had good binding activities with PI3K and AKT-related proteins.The in vitro results showed that JTTF significantly alleviated PA-induced HepG2 cell injury,increased HepG2 glucose consumption,increased PI3K and AKT mRNA and protein expression,regulated the expression of GLUT2,GLUT4 and GSK3β,and improved cellular IR.Conclusion JTTF increases insulin sensitivity of HepG2-IR cells,promotes glucose uptake and intracellular glucose metabolism process,and its mechanism of action may be related to the up-regulation of PI3K/AKT signalling pathway.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

OBJECTIVE Aimed to comprehensively evaluate various immunological changes in a mouse model of eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP)induced by ovalbumin(OVA)combined with Aspergillus protease(AP),including nasal polyps-like lesions,subepithelial collagen deposition,inflammatory cell infiltration,epithelial barrier function,and olfactory neuron damage.METHODS C57BL/6 mice were challenged with OVA and AP for 12 weeks.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe the changes of nasal polyps-like lesions,goblet cell hyperplasia,and subepithelial collagen deposition.Immunohistochemistry staining(IHC)was employed to detect the changes of various inflammatory cells,olfactory neurons,and the expression of epithelial tight junction proteins in the nasal and sinus mucosa.RESULTS Compared to the control group,the OVA and AP group showed significantly increased epithelial thickness,noticeable nasal polyps-like lesions,marked subepithelial collagen deposition,and goblet cell hyperplasia in the nasal and sinus mucosa.IHC results revealed a significant increase in eosinophils,along with higher numbers of neutrophils,mast cells,and CD4+T cells in the OVA and AP group.Additionally,the expression of tight junction proteins ZO-1 and E-cadherin in the nasal and sinus mucosa and the area of OMP+olfactory neurons in the olfactory epithelium were significantly lower in the OVA and AP group compared to the control.CONCLUSION Continuous exposure to OVA combined with AP successfully induces ECRSwNP.The establishment of this model provides a foundation for further research into the pathogenesis and the evaluation of new therapeutic strategies for ECRSwNP.

Objective To investigate the relationship between the levels of soluble FMS-like tyrosine ki-nase-1(sFlt-1),monocyte chemoatgulant protein-1(MCP-1),and soluble lectin-like oxidized low-density lipo-protein receptor 1(sLOX-1)in the serum of patients with coronary heart disease and the disease state and prognosis.Methods A total of 126 patients with coronary heart disease treated in Zhongshan Hospital,Dalian University from May 2022 to May 2024 were selected as study objects.The patients were divided into good prognosis group(n=78)and poor prognosis group(n=48)according to prognostic results.The serum sFlt-1,MCP-1 and sLOX-1 levels were detected by enzyme-linked immunosorbent assay.The degree of coronary artery stenosis in patients was measured by coronary angiography,as indicated by the Gensini score.Spearman correlation analysis was used to analyze the correlation between Gensini score and serum sFlt-1,MCP-1 and sLOX-1 levels.Multivariate Logistic regression was used to analyze the factors affecting the prognosis of pa-tients with coronary heart disease.The predictive efficacy of serum sFlt-1,MCP-1 and sLOX-1 levels for the prognosis of patients with coronary heart disease was evaluated by receiver operating characteristic(ROC)curve.Results The age in the poor prognosis group was older than that in the good prognosis group(P＜0.05),Gensini score was higher than that in the good prognosis group(P＜0.05).Compared with the poor prognosis group,the serum sFlt-1,MCP-1 and sLOX-1 levels in the good prognosis group were lower(P＜0.05).Gensini score was positively correlated with the serum sFlt-1,MCP-1 and sLOX-1 levels.Multivariate Logistic regression analysis showed that old age,high Gensini score,high sFlt-1 level,high MCP-1 level and high sLOX-1 level were all risk factors effecting the prognosis of patients with coronary heart disease(P＜0.05).ROC curve analysis showed that the areas under the curve(AUC)of serum sFlt-1,MCP-1,and sLOX-1 for predicting the prognosis of coronary heart disease patients were 0.787(95％CI:0.703-0.870),0.815(95％CI:0.741-0.890)and 0.795(95％CI:0.715-0.876),respectively.The AUC for predicting the prognosis of coronary heart disease patients using a combination of three was 0.923(95％CI:0.876-0.970).Conclusion The serum levels of sFlt-1,MCP-1 and sLOX-1 in patients with coronary heart disease are signifi-cantly increased,and are positively correlated with the degree of coronary artery stenosis.The levels of sFlt-1,MCP-1 and sLOX-1 in serum have a certain predictive effect on the prognosis of patients with coronary heart disease.