Ischemic stroke is the most common type of stroke,characterized by a complex pathophysiology in which inflammato-ry responses play a pivotal role,significantly affecting patient outcomes.Following a stroke,the disruption of the blood-brain barrier facilitates interactions between the central nervous system(CNS)and the peripheral immune system,triggering a cascade of inflammatory responses that exacerbate ischemic brain injury.Microglia(MG),as the primary immune cells of the CNS,are highly sensitive to cerebral ischemia and interact with various peripheral immune cells to regulate the inflammatory response.For instance,neutrophils participate in early MG-mediated in-flammatory responses through the release of neutrophil extracel-lular traps;T cells interact with MG,exerting bidirectional effects on the spread of brain inflammation and tissue repair.Additionally,other immune cells such as B cells,monocytes/macrophages,and dendritic cells contribute to these processes through complex immune regulatory networks,influencing MG's inflammatory functions and its capacity for tissue repair.This re-view delves into the interaction mechanisms between MG and pe-ripheral immune cells,providing novel insights into the dynamic changes of post-stroke inflammation and potential directions for precision therapies aimed at modulating immune balance.

Objective:To explore the effect of Shenxianling granules on the pharmacokinetics of ondansetron. Methods:A method for detecting the plasma concentration of ondansetron using highperformance liquid chromatography (HPLC) was established. The reliability of the method was validated through specificity, linear relationship, precision, stability, repeated experiments, and sample recovery rate testing. Thirty six healthy male New Zealand rabbits were randomly divided into 2 groups, with 18 rabbits in each group. Rabbits in the single ondansetron group (single drug group) received intravenous injection of ondansetron 0.92 mg/kg through the ear vein. Rabbits in the Shenxianling granules combined with ondansetron group (combination drug group) were firstly given 575 mg/kg of Shenxianling granules by gavage continuously for 10 days, and on the morning of the 11th day, ondansetron 0.92 mg/kg was intravenously injected. Blood samples were collected before administration and at 5 minutes, 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours and 24 hours after administration of ondansetron. The blood concentration of ondansetron was detected using HPLC method and pharmacokinetic parameters were calculate. Results:Two New Zealand rabbits in the combination drug group developed agitation and cough, and then died on the second and fifth day of gavage, respectively. Therefore a total of 18 and 16 rabbits in the single drug group and the combination drug group completed the experiment, respectively. After ondansetron administration, the plasma concentration of ondansetron increased rapidly in the single drug group and remained at low levels in the combination drug group. From 5 minutes to 10 hours after administration, the plasma concentration of ondansetron at the 13 blood sampling time points in the combination drug group was significantly lower than that in the single drug group, and the differences were statistically significant (all P<0.001). Compared with the single drug group, the plasma clearance half-life of ondansetron in the combination drug group was significantly prolonged, the peak time, peak concentration, concentration at the last time and area under the curve (AUC) were all significantly reduced, and the percen- tage of residual or extrapolated area to the overall AUC, apparent volume of distribution, and clearance/bioavailability ratio were significantly increased; the differences were statistically significant (all P<0.001). Conclusions:There is a significant interaction between Shenxianling granules and ondansetron, leading to a decreased plasma concentration of ondansetron. The mechanism may be related to Shenxianling granules altering the tissue distribution of ondansetron within the body.

Objective:To develop habitat radiomics models to predict early treatment responses to the hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy or immunotherapy in advanced hepatocellular carcinoma (HCC) patients, and to guide clinical diagnosis and treatment.Methods:From October 2021 to Decemeber 2023, at Army Characteristic Medical Center of PLA (Chongqing Daping Hospital) and the First Affiliated Hospital of Chongqing Medical University, 94 patients with advanced HCC who received HAIC combined with targeted therapy or immunotherapy were retrospectively enrolled. According to the treatment results, the patients were divided into response group and non-response group. Univariate and multivariate logistic regression were performed to analyze the clinical data of the patients. Based on contrast-enhanced CT images, tumor habitats were delineated and habitat features were extracted with k-means clustering, and the imaging features of arterial and venous phases were also extracted. The least absolute shrinkage and selection operator (LASSO) was used for dimensionality reduction. Feature selection was performed using LASSO to reduce dimensions, and then the selected features were further refined through stepwise logistic regression analysis.Binary logistic regression models were conducted to develop the habitat radiomics model, arterial phase radiomics model (APRM), venous phase radiomics model (VPRM), clinical data model, as well as the combination of radiomics model and clinical data model to predict early treatment (after 2 treatment cycles) response. Receiver operating characteristic curves (ROC) were plotted, and model performance was evaluated by the area under the curve (AUC), calibration curves, and decision curve. The models were validated through Bootstrap methods (1 000 times). DeLong test was used to compare AUC values.Results:The results of cluster analysis identified 3 characteristic habitats in HCC imaging: low-, medium-, and high-enhancement tumor habitats. The proportion of high-enhancement habitats was higher than that in the non-response group. A predictive model was established based on the proportions of these 3 habitats. Based on the proportion of low-, medium-, and high-enhancement habitats within the tumor, a habitat radiomics model was constructed. After LASSO selection and logistic regression analysis, 3 arterial phase and 3 venous phase radiomic features were selected to build the APRM and VPRM, respectively. Logistic regression analysis identified the following factors for the clinical data model: comorbidities ( OR=0.275, P=0.031), maximum tumor diameter ( OR=1.149, P=0.019), red blood cell count ( OR=0.463, P=0.022), alpha fetoprotein >400 μg/L ( OR=3.452, P=0.017), and tyrosine kinase inhibitor therapy ( OR=3.072, P=0.048). Among the single predictive model′s comparison, the AUC of habitat radiomics model was 0.860 (95% confidence interval(95% CI): 0.789 to 0.932), while those of the APRM、VPRM and clinical data model were 0.850 (95% CI: 0.773 to 0.926), 0.855 (95% CI: 0.782 to 0.928), and 0.774 (95% CI: 0.681 to 0.867), respectively, and there were no statistically significant among these models (all P>0.05). Among the combination models, the AUC of the habitat rediomic-clinical data combination model was 0.881 (95% CI: 0.814 to 0.947); the AUC of arterial phase rediomic-clinical data combination model was 0.897 (95% CI: 0.833 to 0.961); and the AUC of venous phase rediomic-clinical data combination model was 0.888 (95% CI: 0.826 to 0.951), but there were no statistically significant among the 3 models (all P>0.05). The calibration curve showed that the habitat rediomic-clinical data combination model had the most accurate predictive probability. Internal validation showed that the AUC of habitat rediomic-clinical data combination model was 0.848 (95% CI: 0.772 to 0.922), and the predictive performance was better than that of the clinical-data model (0.733 (95% CI: 0.670 to 0.863)). Conclusion:The habitat radiomics model based on enhanced CT can effectively predict early treatment responses to the HAIC combined with targeted therapy or immunotherapy in advanced HCC patients, which provides theoretical basis for individualized treatment in advanced HCC.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.

Objective:To observe the effects of Sitting Baduanjin combined with Sacubitril/Valsartan on cardiopulmonary function,exercise capacity and vascular endothelial function in patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods:A retrospective analysis was conducted on the clinical data of 86 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)at Zhangzhou Third Hospital from April 2023 to August 2024,among these patients,43 were treated with a combination of Sacubitril/Valsartan and Sitting Baduanjin,forming the study group,the other 43 patients,treated with sacubitril/valsartan alone,were randomly assigned in a 1∶1 ratio to form the control group.The cardiopulmonary function[cardiac index(CI),left ventricular ejection fraction(LVEF),The ratio of forced expiratory volume to forced vital capacity(FEV/FVC),maximum ventilation volume(MVV)].Exercise capacity[6-minute walking test distance(6MWD),maximum motion load(MWL),peak oxygen uptake(VO2peak)],vascular endothelial function[endothelin-1(ET-1),vascular endothelium-dependent diastolic function(FMD),vascular pseudohematologic factor(vWF)]and the occurrence of adverse cardiovascular events between the two groups were compared.Results:CI,LVEF,FEV/FVC and MVV of the study group at 2 months after intervention were higher than those of the control group(P＜0.05).6MWD,MWL,VO2peak of the study group at 2 months after intervention were higher than those of the control group(P＜0.05).ET-1,vWF of the study group at 2 months after intervention were lower than those of the control group,FMD was higher than that of the control group(P＜0.05).There was no significant difference in the total incidence of adverse cardiovascular events between the two groups(P＞0.05).Conclusion:Sitting Baduanjin combined with Sacubitril/Valsartan can effectively improve the cardiopulmonary function,exercise capacity and vascular endothelial function of patients with coronary heart disease after PCI.

Ischemic stroke is the most common type of stroke,characterized by a complex pathophysiology in which inflammato-ry responses play a pivotal role,significantly affecting patient outcomes.Following a stroke,the disruption of the blood-brain barrier facilitates interactions between the central nervous system(CNS)and the peripheral immune system,triggering a cascade of inflammatory responses that exacerbate ischemic brain injury.Microglia(MG),as the primary immune cells of the CNS,are highly sensitive to cerebral ischemia and interact with various peripheral immune cells to regulate the inflammatory response.For instance,neutrophils participate in early MG-mediated in-flammatory responses through the release of neutrophil extracel-lular traps;T cells interact with MG,exerting bidirectional effects on the spread of brain inflammation and tissue repair.Additionally,other immune cells such as B cells,monocytes/macrophages,and dendritic cells contribute to these processes through complex immune regulatory networks,influencing MG's inflammatory functions and its capacity for tissue repair.This re-view delves into the interaction mechanisms between MG and pe-ripheral immune cells,providing novel insights into the dynamic changes of post-stroke inflammation and potential directions for precision therapies aimed at modulating immune balance.

Objective:To observe the effects of Sitting Baduanjin combined with Sacubitril/Valsartan on cardiopulmonary function,exercise capacity and vascular endothelial function in patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods:A retrospective analysis was conducted on the clinical data of 86 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI)at Zhangzhou Third Hospital from April 2023 to August 2024,among these patients,43 were treated with a combination of Sacubitril/Valsartan and Sitting Baduanjin,forming the study group,the other 43 patients,treated with sacubitril/valsartan alone,were randomly assigned in a 1∶1 ratio to form the control group.The cardiopulmonary function[cardiac index(CI),left ventricular ejection fraction(LVEF),The ratio of forced expiratory volume to forced vital capacity(FEV/FVC),maximum ventilation volume(MVV)].Exercise capacity[6-minute walking test distance(6MWD),maximum motion load(MWL),peak oxygen uptake(VO2peak)],vascular endothelial function[endothelin-1(ET-1),vascular endothelium-dependent diastolic function(FMD),vascular pseudohematologic factor(vWF)]and the occurrence of adverse cardiovascular events between the two groups were compared.Results:CI,LVEF,FEV/FVC and MVV of the study group at 2 months after intervention were higher than those of the control group(P＜0.05).6MWD,MWL,VO2peak of the study group at 2 months after intervention were higher than those of the control group(P＜0.05).ET-1,vWF of the study group at 2 months after intervention were lower than those of the control group,FMD was higher than that of the control group(P＜0.05).There was no significant difference in the total incidence of adverse cardiovascular events between the two groups(P＞0.05).Conclusion:Sitting Baduanjin combined with Sacubitril/Valsartan can effectively improve the cardiopulmonary function,exercise capacity and vascular endothelial function of patients with coronary heart disease after PCI.

Objective:To construct a nursing quality evaluation indicator system for pulse indicator continuous cardiac output (PiCCO) monitoring and provide a basis for evaluating the nursing quality of PiCCO monitoring.Methods:Using Donabedian′s "structure-process-result" three-dimensional quality evaluation model as the theoretical framework, the nursing quality evaluation indicator system for PiCCO was established through literature search, Delphi expert correspondence, and hierarchical analysis during the period May to August 2023.Results:Of the 22 experts, 6 were male and 16 were female, aged (46.59 ± 4.34) years. The return rates of the questionnaires of the 2 rounds of expert correspondence were both 100%, the coefficients of expert authority were both 0.945, and the Kendall coordination coefficients were 0.045-0.186 ( χ2 values were 2.00-221.46, all P<0.05) and 0.045-0.132 ( χ2 values were 2.00-82.16, all P<0.05), respectively. The finalized nursing quality evaluation indicator system for PiCCO included 3 primary indicators, 7 secondary indicators, and 36 tertiary indicators. Conclusions:The nursing quality evaluation indicator system for PiCCO is practical and scientific, which can provide reference for PiCCO monitoring nursing quality evaluation.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.