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.

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 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 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.

Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP)in a hospital in Hainan Province,explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP(hv-CRKP)and non-hv-CRKP,analyze the clinical significance,and provide basis for optimizing treatment and prevention strategies.Methods CRKP strains isolated from a hospi-tal in Hainan Province from July 2023 to June 2024 were collected retrospectively.Their resistance phenotypes were detected by antimicrobial susceptibility testing.Carbapenemase genes(KPC-2,NDM-1,IPM)and virulence factors(rmpA/rmpA2,iucA,iroB,etc.)were detected by polymerase chain reaction(PCR).Department source,speci-men distribution,and resistance-virulence characteristics were analyzed.Results A total of 76 strains of CRKP were isolated,with an overall isolation rate of 7.7％(76/985).The strains were mainly distributed in the intensive care unit(ICU)(28.9％)and neurosurgery ICU(23.6％),with the highest proportion of strains isolated from re-spiratory tract specimens(60.5％).The resistance genes were mainly KPC-2(72.4％)and NDM-1(21.1％),and the virulence factors mrkD(type Ⅲ pili,85.5％)and fim H(type Ⅰ pili,84.2％)were commonly presented.Among 76 strains of CRKP,39 strains(51.3％)met the criteria for hv-CRKP and all carried KPC-2 gene(100％).The detection rates of resistance genes and virulence factors rmpA2(97.4％),iucA(100％),and iroB(89.7％)were all higher than those of non-hv-CRKP strains(KPC-2,43.2％;rmpA2,0;iucA,8.1％;iroB,13.5％).The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors(64.1％).Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP.hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP.Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable.hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors,and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP.Both are generally resistant to β-lactams and quinolones.hv-CRKP has lower resistance rates to aminoglycosides and com-pound sulfamethoxazole than non-hv-CRKP.Its advantage of aminoglycoside susceptibility provides a new treatment option.It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.

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 investigate shared mechanisms and therapeutic targets between heart failure(HF)and vascular de-mentia(VaD),and identify natural compounds for dual-organ protection.Methods Single-cell data(8 samples)from GEO were processed via Seurat for clustering.Through CellChat,inter-organ communication was constructed,and top 95%ligand-receptor pairs were analyzed by KEGG enrichment.Bulk RNA-seq(70 samples)underwent differential gene(limma)and immune infiltra-tion(CIBERSORT)analyses.31186 compounds from TCMbank werescreened by AutoDock Vina,followed by molecular dynam-ics validation.Results HF fibroblasts(43.75%,7 subclusters)and VaD oligodendrocytes(76.57%,6 subclusters)dominated re-spective tissues.Cross-disease integration revealed HF-driven fibrosis(COLLAGEN)and VaD-associated neuroinflammation(SPP1),converging on PI3K-Akt and ECM pathways.HF-specific markers(TNXB/THBS4/COL1 A2)and VaD signatures(SPP1/PDGFC/TGFA)were identified,with FOXC1 identified as a shared transcriptional regulator.B cell activation character-ized immune dysregulation.Among 8 FOXC1 inhibitors,Qingdainone showed optimal binding[affinity:-9.0 kcal/mol;RMSD:(0.2±0.06)nm].Conclusion This study uncovers fibrosis-neuroinflammation crosstalk in HF-VaD comorbidity and proposes Qingdainone as a FOXC1-targeting therapeutic candidate.

The purpose of this study was to investigate the effect of medium-chain fatty acids(MC-FAs)caprylic acid(C8∶0)on lipid metabolism of calf hepatocytes.Primary calf hepatocytes were extracted and cultured,and 1.2 mmol/L nonesterified fatty acids(NEFAs)were added to the hep-atocytes to construct a model of hepatic lipid deposition in primary calf hepatocytes,Five process-ing groups have been set up:Control group(Ctrl),NEFA added group(NEFA),C8∶0 1.2 mmol/L treatment group(C8∶0 1.2),NEFA+C8∶0 0.2 mmol/L treatment group(NEFA+C8∶00.2),C8∶0 0.2 mmol/L treatment group(C8∶0 0.2).Stimulate calf liver cells for 12 hours,and the levels of triglyceride(TG),lipid oxidation(MDA),hydrogen peroxide(H2O2)and total SOD activity were detected by biochemical kit,and FAS,a protein related to lipid synthesis,was detec-ted by Western blot.The results showed that compared with the control group,the concentrations of TG,MDA and H2O2 in NEFA group increased significantly(P＜0.01),and the activity of SOD decreased significantly(P＜0.05).The protein expression levels of FAS,ACC1,DGAT2 and SREBP-1C were significantly up-regulated(P＜0.01),while the expression level of CPT1A was significantly down-regulated(P＜0.01).Compared with the NEFA group,the protein expression levels of SREBP-1C and DGAT2 in the NEFA+C8∶0(concentration 0.2 mmol/L)group de-creased significantly(P＜0.05),and the protein expression level of fatty acid β-oxidation related molecule CPT1A was slightly higher than that in the NEFA group,but there was no statistical sig-nificance(P＞0.05),and the MDA level in hepatocytes decreased significantly(P＜0.05).In a word,the results of this study show that C8∶0 has antioxidant effect,which can effectively reduce the liver injury caused by oxidative stress,regulate the expression of liver fat gene,and then pro-tect liver injury.

Objective To analyze the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae(CRKP)in a hospital in Hainan Province,explore the differences in the distribution of resistance genes and virulence factors between hypervirulent CRKP(hv-CRKP)and non-hv-CRKP,analyze the clinical significance,and provide basis for optimizing treatment and prevention strategies.Methods CRKP strains isolated from a hospi-tal in Hainan Province from July 2023 to June 2024 were collected retrospectively.Their resistance phenotypes were detected by antimicrobial susceptibility testing.Carbapenemase genes(KPC-2,NDM-1,IPM)and virulence factors(rmpA/rmpA2,iucA,iroB,etc.)were detected by polymerase chain reaction(PCR).Department source,speci-men distribution,and resistance-virulence characteristics were analyzed.Results A total of 76 strains of CRKP were isolated,with an overall isolation rate of 7.7％(76/985).The strains were mainly distributed in the intensive care unit(ICU)(28.9％)and neurosurgery ICU(23.6％),with the highest proportion of strains isolated from re-spiratory tract specimens(60.5％).The resistance genes were mainly KPC-2(72.4％)and NDM-1(21.1％),and the virulence factors mrkD(type Ⅲ pili,85.5％)and fim H(type Ⅰ pili,84.2％)were commonly presented.Among 76 strains of CRKP,39 strains(51.3％)met the criteria for hv-CRKP and all carried KPC-2 gene(100％).The detection rates of resistance genes and virulence factors rmpA2(97.4％),iucA(100％),and iroB(89.7％)were all higher than those of non-hv-CRKP strains(KPC-2,43.2％;rmpA2,0;iucA,8.1％;iroB,13.5％).The main characteristics of hv-CRKP was the combination of KPC-2 resistance gene and rmpA2+iucA+iutA+iroB virulence factors(64.1％).Antimicrobial resistance phenotype of hv-CRKP was different from non-hv-CRKP.hv-CRKP presented higher susceptibility rates to aminoglycosides and compound sulfamethoxazole than non-hv-CRKP.Conclusion The proportion of hv-CRKP and non-hv-CRKP strains in this hospital is comparable.hv-CRKP is characterized by carrying the KPC-2 resistance gene in combination with rmpA2+iucA+iutA+iroB virulence factors,and the proportion of strains carrying multiple virulence factors is higher than that of non-hv-CRKP.Both are generally resistant to β-lactams and quinolones.hv-CRKP has lower resistance rates to aminoglycosides and com-pound sulfamethoxazole than non-hv-CRKP.Its advantage of aminoglycoside susceptibility provides a new treatment option.It is recommended to guide differential medication through molecular typing and strengthen infection control measures in ICU to curb the spread of antimicrobial-resistant bacteria.

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.