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.

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 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 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 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.

Objective:To analyze the association between unhealthy lifestyles and depressive symptoms, anxiety symptoms and stress among secondary school students in Jiangsu Province.Methods:From September to November 2023, a multistage stratified cluster random sampling method was used to select secondary school students from 13 districts and cities in Jiangsu Province. A questionnaire survey was conducted on their unhealthy lifestyles (low physical activity, smoking, drinking, internet addiction, poor sleep quality, and unhealthy diet), as well as their depressive symptoms, anxiety symptoms and stress. The multivariate logistic regression model and mixed graph model were used to construct a network and analyze the association between unhealthy lifestyles and depressive symptoms, anxiety symptoms and stress.Results:A total of 81 414 secondary school students were finally included in this study, including 39 725 (48.79%) female students and 41 689 (51.21%) male students. The prevalence of depressive symptoms, anxiety symptoms and stress were 18.55%, 32.09% and 12.91%, respectively. The multivariate logistic regression model showed that after adjusting for age, gender, urban-rural status, residential status, and family type, compared with students without unhealthy lifestyles, students with low physical activity, smoking, alcohol consumption, internet addiction, poor sleep quality, and unhealthy diet had a significantly increased risk of depressive symptoms ( OR=1.12, 95% CI:1.07-1.17; OR=1.60, 95% CI: 1.49-1.72; OR=1.79, 95% CI: 1.71-1.88; OR=3.05, 95% CI: 2.77-3.36; OR=6.66, 95% CI: 6.40-6.93; OR=1.29, 95% CI: 1.24-1.34) and a significantly increased risk of anxiety symptoms ( OR=1.09, 95% CI: 1.05-1.13; OR=1.42, 95% CI: 1.33-1.52; OR=1.76, 95% CI: 1.69-1.83; OR=2.40, 95% CI: 2.17-2.65; OR=5.79, 95% CI: 5.59-6.00; OR=1.16, 95% CI: 1.12-1.21). Students who smoked, drank alcohol, had internet addiction, and had poor sleep quality had a significantly increased risk of stress ( OR=1.49, 95% CI: 1.38-1.61; OR=1.79, 95% CI: 1.70-1.89; OR=2.25, 95% CI: 2.04-2.48; OR=6.74, 95% CI: 6.43-7.06). The node with poor sleep quality (bridge strength=0.48) in the network constructed by the mixed graph model had the strongest centrality of the bridge connecting unhealthy lifestyles with depressive symptoms, anxiety symptoms and stress. Conclusion:Low physical activity, smoking, alcohol consumption, internet addiction, poor sleep quality, and unhealthy diet increase the risk of depressive symptoms and anxiety symptoms among Jiangsu Province secondary school students. Smoking, alcohol consumption, internet addiction, and poor sleep quality increase the risk of stress among Jiangsu Province secondary school students. Sleep quality is an important intervention target for Jiangsu Province secondary school students to alleviate their negative emotions.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.