ObjectiveTo investigate the mechanism by which Xiebai San regulates respiratory tract and intestinal mucosal immunity in rats with allergic asthma. MethodsForty male SD rats were randomly divided into four groups based on body weight: control group, model group, positive control group, and Xiebai San group. The model group, positive control group, and Xiebai San group were sensitized with ovalbumin to establish a rat model of allergic asthma. From day 21 (the aerosol challenge phase), each group received daily gavage interventions simultaneously: the positive control group was administered dexamethasone (0.068 mg/kg), the Xiebai San group received Xiebai San solution (2 g/mL, 11.3 mL/kg), while the control and model groups were given an equal volume of normal saline, once daily for 14 consecutive days. After euthanasia, lung and intestinal tissues were collected. Hematoxylin and eosin staining was used to observe histopathological changes. Transmission electron microscopy was employed to examine tissue ultrastructure. Immunohistochemistry was applied to detect the positive reaction areas of phosphatidyl-inositol 3-kinase (PI3K) and protein kinase B (Akt) proteins. Total protein and total RNA were extracted from lung and intestinal tissues, then the protein and mRNA expression levels of PI3K and Akt genes were detected by Western blotting and real-time quantitative PCR, respectively. ResultsHistopathological results showed alveolar emphysema accompanied by inflammatory cell infiltration, and intestinal mucosal injury with inflammatory cell infiltration in the model group as compared with the control group; the cellular structure of lung tissues was disrupted in the model group, with reduced organelles, while the ultrastructural lesions in the intestine were relatively mild. Compared with the model group, Xiebai San group exhibited milder pathological changes in lung tissues, with occasional alveolar wall damage and a small amount of inflammatory cell infiltration; the intestinal mucosal structure was improved, glands were arranged regularly, and pathological changes such as tissue loosening and inflammatory infiltration were alleviated; the cellular structure of lung tissues was relatively intact with reduced severity of lesions, and no ultrastructural pathological changes were observed in intestinal tissues. Immunohistochemistry and Western blotting results showed that compared with the control group, the specific positive reaction areas of PI3K and Akt in lung and intestinal tissues were significantly increased in the model group (all P<0.001); meanwhile, the protein expression levels of PI3K and Akt were significantly upregulated (all P<0.05). Compared with the model group, the positive area of Akt protein in lung tissue was significantly reduced in the Xiebai San group (P<0.001), and the positive area of PI3K in intestinal tissue was also significantly decreased (P<0.000 1). Additionally, the protein expression levels of PI3K and Akt in lung and intestinal tissues were significantly downregulated (all P<0.01). Real-time quantitative PCR results showed that compared with the control group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly elevated in the model group (all P<0.05). Compared with the model group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly reduced in the Xiebai San group (all P<0.05). ConclusionXiebai San exerts protective effects on rats with allergic asthma by inhibiting the expression of key nucleic acids and proteins in the PI3K-Akt signaling pathway in lung and intestinal tissues, improving the morphological structure of lung tissue, and maintaining intestinal mucosal integrity, and regulating intestinal mucosal immune function.

Objective To prepare glucose transporter 1(Glut1)-targeted doxorubicin(DOX)-loaded liposomes(doxorubicin/polyphyllin H-liposomes,DOX/ppH-LPs)using polyphyllin H(ppH)instead of cholesterol as the liposomal membrane material,and to investigate their in vitro synergistic anti-tumor activity against non-small cell lung cancer(NSCLC).Methods DOX/ppH-LPs were prepared using thin-film hydration,and the formulation was optimized by single-factor investigation.The optimized DOX/ppH-LPs were characterized for morphology,particle size,polydispersity index(PDI),and zeta potential with transmission electron microscopy(TEM)and dynamic light scattering(DLS).Drug loading DL%was determined by high-performance liquid chromatography(HPLC).The storage stability was evaluated by observing in PBS at 4℃for 7 d,and the serum stability was observed in DMEM containing 10%fetal bovine serum(FBS)at 37℃for 48 h.In vitro drug release was studied in PBS at pH 7.4 and pH 5.0 values,respectively.Human NSCLC A549 cells were subjected as the model,MTT assay was performed to detect the proliferation inhibition by DOX/ppH-LPs at different concentrations(0.5,5.0,15.0 μg/mL)and the control group(ppH+DOX/LPs,a physical mixture of free ppH and DOX-loaded liposomes).Fluorescence microscopy was used to observe cellular uptake of DOX/ppH-LPs and DOX/LPs(containing 5 μg/mL DOX)at 15 min and 2 h.Live/dead cell staining was applied to assess apoptosis/necrosis induced by formulations(15 μg/mL DOX)after 48 h incubation.Transwell assay was conducted to evaluate inhibitory effect on cell migration and invasion,and the targeting property and in vitro synergistic anti-NSCLC activity of DOX/ppH-LPs were then comprehensively evaluated.Results The optimal formulation of DOX/ppH-LPs was determined as hydration temperature at 50℃,6 mg DOX,2 mg ppH,and 24 mg lecithin.The prepared DOX/ppH-LPs were in spherical shape,uniform distribution,and at an average particle size of 145.13±22.14 nm,a PDI of 0.15±0.05,a zeta potential of-23.92±1.73 mV,and a DL of 10.13±0.71%for DOX and(1.22±0.21)%for ppH.DOX/ppH-LPs maintained stable particle size,PDI,and exhibited significantly unchanged zeta potential after storage in PBS at 4℃for 7 d or incubation in DMEM containing 10%FBS at 37℃for 48 h,demonstrating excellent physical and serum stability.Both liposomes showed slow release at pH 7.4 value,while drug release was significantly accelerated at pH 5.0 value(P<0.05),indicating pH-sensitive release characteristics.MTT assay revealed that DOX/ppH-LPs exerted significantly stronger cytotoxicity against A549 cells than the ppH+DOX/LPs control group(P<0.05).Compared with ppH+DOX/LPs,DOX/ppH-LPs showed remarkably enhanced cellular uptake in A549 cells(P<0.05),with more DOX localized in the nucleus.Live/dead cell staining showed that at the same DOX concentration(15 μg/mL),the proportion of apoptotic/necrotic cells induced by DOX/ppH-LPs was significantly higher than that of the DOX/LPs control group.Transwell assay demonstrated that there were significantly less cells migrating and invading through the membrane in the DOX/ppH-LPs group than the ppH+DOX/LPs group.Conclusion Glut1-targeted doxorubicin-loaded liposomes(DOX/ppH-LPs)constructed by substituting cholesterol with ppH can target NSCLC cells,significantly enhance the in vitro synergistic anti-NSCLC activity of DOX and ppH.

Attention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder influenced by both genetic and environmental factors, remains poorly understood regarding how its polygenic risk score (PRS) impacts functional networks and symptomology. This study capitalized on data from 11,430 children in the Adolescent Brain Cognitive Development study to explore the interplay between PRS_ADHD, brain function, and behavioral problems, along with their interactive effects. The results showed that children with a higher PRS_ADHD exhibited more severe attention deficits and rule-breaking problems, and experienced sleep disturbances, particularly in initiating and maintaining sleep. We also identified the central executive network, default mode network, and sensory-motor network as the functional networks most associated with PRS and symptoms in ADHD cases, with potential mediating roles. Particularly, the impact of PRS_ADHD was enhanced in children experiencing heightened sleep disturbances, emphasizing the need for early intervention in sleep issues to potentially mitigate subsequent ADHD symptoms.
Humans ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Male ; Female ; Sleep Wake Disorders/physiopathology* ; Adolescent ; Child ; Brain/diagnostic imaging* ; Multifactorial Inheritance ; Genetic Predisposition to Disease

Gastric cancer,which has high incidence and mortality rates worldwide,faces numerous challenges in its diagnosis and treatment.In recent years,the combination of multi-omics technology and artificial intelligence(AI)algorithms has brought new hope for the diagnosis and treatment of this malignant disease.Multi-omics technology encompasses the fields of genomics,transcriptomics,proteomics,meta-bolomics,and radiomics,and can comprehensively reveal the biological characteristics of gastric cancer.AI algorithms,particularly machine-and deep-learning methods,possess powerful data integration,feature extraction,and pattern recognition capabilities,enabling the extrac-tion of the most valuable information from vast and complex multi-omics data.Such technology can aid in the early screening,precise dia-gnosis,personalized treatment,and prognostic assessment of gastric cancer.In this article,research progress on AI-based multi-omics tech-nology for the diagnosis and treatment of gastric canceris reviewed,and current applications of such technology at different diagnostic and therapeutic stages,the challenges faced,and future development directions are discussed,with the aim of providing new ideas and meth-ods for the diagnosis and treatment of this malignant disease.

Objective:To explore the relationship between blood urea nitrogen (BUN) levels and the risk of all-in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study, with data sourced from the DATADRYAD database of five hospitals in Japan (Kameda Hospital, Hyogo Hospital, Awa Hospital, Saiseikai Hospital, and Ichinomiyanishi Hospital). The database included 1 237 cases of AECOPD with pneumonia hospitalized from April 2008 to August 2019, aged≥40 years. After excluding 11 cases with missing BUN level data at admission, a total of 1 226 patients were included in this secondary analysis. BUN level at admission was used as the target independent variable, and all-cause in-hospital mortality during hospitalization was the dependent variable. Risk ratio regression analysis was used to assess the independent correlation between BUN level and the risk of in-hospital mortality due to AECOPD complicated with pneumonia; generalized additive models and smoothing curve fitting methods were applied to explore nonlinear relationships, followed by subgroup analyses to evaluate the consistency of the association across different subgroups and further validate the reliability of the findings.Results:After adjusting for potential confounding factors such as gender and age, BUN levels were positively correlated with the risk of all-cause in-hospital mortality [ OR=1.09(95% CI: 1.01-1.17), P=0.032]. There was a relationship between BUN levels and the risk of all-cause in-hospital mortality, with a turning point at 43.3 mg/dl. The sizes and 95% CI on either side of the turning point were 1.04(0.93-1.16) and 1.08(1.05-1.12), respectively. When BUN>43.3 mg/dl, BUN was correlated with the risk of all-cause in-hospital mortality, with an 8.0% increase in the risk of death for every 1.0 mg/dl increase in BUN ( P<0.05); when BUN<43.3 mg/dl, there was no significant relationship between BUN and the risk of all-cause in-hospital mortality ( P=0.534). Subgroup analysis indicated that in each subgroup of gender, age, source hospital, fever, respiratory, heart rate, crackles in the lungs, change in mental status, corticosteroid therapy, intubation, complete assistance with activities of daily living, medical insurance, and length of hospital stay, the OR value of BUN level had good stability (all OR>1.00) with the risk of all-cause mortality in AECOPD patients with pneumonia. Conclusions:BUN levels are associated with the risk of all-cause in-hospital mortality in patients with AECOPD complicated with pneumonia. When BUN>43.3 mg/dl, BUN levels are positively correlated with the risk of all-cause in-hospital mortality in these patients.

Objective:To explore the value of fetal heart quantification technology in assessing the morphology and function of the fetal heart during normal pregnancy.Methods:This prospective cohort study selected normal fetuses from healthy pregnant women who underwent prenatal ultrasound examinations at Hunan Provincial People's Hospital from January 2023 to October 2024. Using the GE Voluson E10 color Doppler diasonography, routine obstetric ultrasound and fetal echocardiography were performed to assess fetal growth and development and to exclude intracardiac and extracardiac malformations. Clear four-chamber view (4CV) dynamic images of the heart showing the endocardium (duration ≥3 s) were collected. Speckle-tracking analysis was performed using fetal heart quantification software. The measured indicators included the global spherical index (GSI), end-diastolic length of the heart (L-ED), end-diastolic width of the heart (W-ED), and the global longitudinal strain (GLS), fractional area change (FAC), and 24-segment spherical index (SI) of the left ventricle (LV) and right ventricle (RV). The cases were divided into five groups based on gestational age at the time of prenatal ultrasound: 20 +0 to 23 +6, 24 +0 to 27 +6, 28 +0 to 31 +6, 32 +0 to 35 +6, and 36 +0 to 40 +6 weeks. One-way analysis of variance, two independent samples t-test, univariate linear regression analysis, and Pearson correlation analysis were used to explore the differences in the above indicators among different gestational age groups and their correlation with gestational age. Results:A total of 200 pregnant women were included in the cohort, four cases were excluded due to poor image quality that prevented accurate tracking and measurement of relevant indicators. Ultimately, 196 cases (20 +0 to 23 +6 weeks 40 cases, 24 +0 to 27 +6 weeks 34 cases, 28 +0 to 31 +6 weeks 41 cases, 32 +0 to 35 +6 weeks 48 cases, and 36 +0 to 40 +6 weeks 33 cases) were included in the study, with a successful image analysis rate of 98.0%. (1) There were statistically significant differences in 4CV L-ED, 4CV W-ED, LV-FAC, and RV-FAC among the groups at 20 +0 to 23 +6, 24 +0 to 27 +6, 28 +0 to 31 +6, 32 +0 to 35 +6, and 36 +0 to 40 +6 weeks [4CV L-ED: 28.0±3.0, 32.6±4.3, 40.9±4.3, 46.7±4.8, 53.1±5.8, F=3.72; 4CV W-ED: 21.9±1.8, 25.1±4.2, 31.7±3.0, 37.4±4.0, 42.0±4.9, F=2.61; LV-FAC: (51.4±8.0)%, (49.0±10.4)%, (47.3±7.3)%, (43.1±7.5)%, (40.7±8.2)%, F=2.94; RV-FAC: (49.9±10.8)%, (46.2±12.0)%, (46.3±8.3)%, (43.2±8.0)%, (41.9±5.6)%, F=3.09; all P<0.05].(2) The size of the normal fetal heart gradually increased with gestational age, while the heart morphology remained relatively stable (4CV L-ED and 4CV W-ED were positively correlated with gestational age, with regression coefficients of 1.313 and 1.325, respectively, both P<0.001;LV-FAC and RV-FAC were negatively correlated with gestational age with regression coefficients of -0.783 and -0.552, respectively, both P<0.001; GSI, LV-GLS and RV-GLS had no correlations with gestational age, all P>0.05). (3) The SI of LV segments 1 to 17 were higher than the SI of the corresponding RV segments, and the SI of RV segments 20-24 were higher than that of the corresponding LV segments (all P<0.001). Conclusion:Fetal heart quantification technology has a certain value in the assessment of fetal cardiac morphology and function.

Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.

Objective This review aims to investigate the application of eye tracking(ET)in patients with speech impairment in the ICU.The review summarizes the current status and prospects of ET technology applications.Methods Following the scoping reviews framework,a systematic search was conducted across Web of Science,PubMed,Cochrane Library,Embase,CINAHL,CNKI,Wanfang Data,Chinese Medical Database,and Chinese biomedical database.The search covered publications from the inception of each database to October 29th,2024.The included studies were comprehensively analyzed.Results A total of 12 pieces of the literature were included,including 4 prospective cohort studies,4 experimental studies,3 prospective observational studies,and 1 randomized controlled trial.The application population of ET in the ICU mainly includes patients on mechanical ventilation,those at high risk of delirium,patients with spinal cord injury,etc.The types of integrated ET system equipment are mainly head-mounted and fixed;the types of ET involve gaze,blinking,etc.;the functions include standardized scale assessment,free interaction,and eye-movement model recognition.The main outcome indicators of the research are feasibility,physical symptoms and social-psychological status.Conclusion ET is applicable to a specific group of ICU patients with aphasia,and has shown good feasibility and effectiveness in the expression of patients'basic needs,self-assessment of symptoms and improvement of psychosocial status.

This paper summarizes the current situation of the cultivation of specialized Traditional Chinese Medicine (TCM) geriatric nursing talents under the background of the integration of medical care and elderly care, including the cultivation status, necessity, feasibility, and existing problems. Based on this, reflections and prospects are put forward, aiming to further promote the cultivation of specialized TCM nursing talents, facilitate the in-depth integration of TCM nursing and geriatric nursing, and drive the high-quality development of nursing.