Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective To analyze the effect and molecular mechanism of phellodendron amurense in the treatment of liver injury based on network pharmacology,and to verify the relevant prediction targets and the protective effect of phellodendron amurense extract-Phellodendron amurense polysaccharide on immune liver injury through mice.Methods TCMSP and Swiss target prediction databases were used to retrieve and screen phellodendron amurenses active components and action targets,and then obtain disease-related targets on GeneCards and OMIM websites,and take compounds and disease intersection targets for protein interaction.Analysis,GO biological function and KEGG signaling pathway enrichment analysis,followed by molecular docking of compounds and key target proteins,and finally established a mouse liver injury model induced by Daodou protein A(Con A)to explore the mechanism of phellodendron amurense extract in the treatment of liver injury.Results 37 active ingredients were screened.The key targets for their treatment were tumor necrosis factor α(TNF-α),serine/threonine protein kinase 1(AKT1),signal transduction and transcription activation factor 3(STAT3),epidermal growth factor receptor(EGFR)anditin.Enzyme 3(CASP3)and other enrichment analysis showed that phellodendron amurense might play a protective role in protecting the liver through molecular mechanisms such as positive regulation of MAPK cas-cade reaction,oxidative stress response and regulatory PI3K-Akt signaling pathway,lipid and atherosclerosis.Ani-mal experiments had found that the gastric treatment of phellodendron amurense polysaccharide could improve the activity of superoxide dismutase(SOD)and catalase(CAT)in liver tissue,reduce the levels of serum alkaline phosphatase(ALP),aspartate aminotransferase(AST)and malonaldehyde(MDA)in liver tissue,and regulate serum inflammatory factor while the expression of intercitin(IL)-6,IL-1 β,tumor necrosis factor α(TNF-α),ac-tivated the expression of transforming growth factor β1(TGF-β1),and reduced TNF-α mRNA expression in liver tissue.Conclusion Phellodendron amurense can intervene in lipid and atherosclerosis pathways by acting on tar-gets such as TNF-α,AKT1,STAT3,EGFR and CASP3 to reduce oxidative stress and inflammatory reactions and achieve liver protection.

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.

Objective To explore the differences of regional homogeneity(ReHo)between overweight and normal weight male patients with type 2 diabetes mellitus(T2DM)during rest and their correlations with clinical features.Methods Twenty-five untreated male overweight T2DM(OW-T2DM)patients,25 untreated male normal weight T2DM(NW-T2DM)patients and 25 healthy controls(HC)were enrolled.The brain structure and resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from all subjects.The brain structure and rs-fMRI data were preprocessed,and ReHo values of all brain regions were calculated for all subjects.ReHo values were compared among three groups and between groups respectively via the methods of one-way analysis of variance and two-sample t-test.To address the problem of multiple comparisons,the method of AlphaSim was performed(the threshold was set at P<0.005,the number of voxel clusters was>12).In addition,Pearson correlation analysis was performed to explore the relationships between ReHo values of the abnormal brain regions and clinical features in patients.Results(1)The brain regions showed differences of ReHo values among three groups were mainly distributed in the right hemisphere,including the superior parietal gyrus,superior marginal gyrus and superior occipital gyrus;(2)Compared with HC,NW-T2DM patients showed significantly decreased ReHo values in the right medial superior frontal gyrus,right middle cingulate gyrus and left anterior cingulate gyrus;(3)Compared with HC,OW-T2DM patients showed significantly decreased ReHo values in the bilateral postcentral gyrus and bilateral middle cingulate gyrus;(4)Compared with NW-T2DM patients,OW-T2DM patients showed significantly decreased ReHo values in the right superior parietal gyrus,right superior occipital gyrus and left cuneus;(5)ReHo values of the right medial superior frontal gyrus and right superior parietal gyrus were negatively correlated with hemoglobinA1c(HbA1c)level and body mass index(BMI),respectively,in all patients.Conclusion The occurrence of T2DM in male patients may lead to the declined activity of brain regions located in the default mode network(DMN),while overweight may further lead to decreased brain activity within the attention and visual recognition network in male T2DM patients.

ObjectiveThe chemical exchange saturation transfer (CEST) technique has become a valuable tool in diagnosing metabolic changes associated with cerebral and systemic diseases, leveraging the calculation of compounds with exchangeable protons in proximity to water molecules. Specifically, the amide proton transfer (APT) CEST technique has shown promise in diagnosing cerebral strokes and tumors by comparing altered endogenous proteins or peptides with normal tissues. Reduced field of view (rFOV) imaging technology has been widely used in the diagnosis of small organ lesions in the body. In this study, we aim to apply the rFOV imaging to identify CEST signals in the rectum, investigating the potential utility of rFOV technique in clinical diagnosis of rectal diseases and providing metabolic insights for chemoradiotherapy. MethodsMRI images of eleven healthy volunteers were acquired using transverse Full_FOV and rFOV CEST imaging on a 3T scanner. The resolution was set at 2.5×2.5×6 mm³ and 1.5×1.5×6 mm³ for Full_FOV or the rFOV method. Saturation powers of 0.7 μT and 2 μT were applied. For the 2 μT saturation, MTRasym at ±3.5 ppm was employed, while for 0.7 μT saturation, Lorentzian difference was used for CEST quantification of the contrast maps and curves. ResultsThe rFOV method has the advantage of halving the scan time while maintaining the same contrast as the Full_FOV method. When compared to Full_FOV methods, rFOV methods exhibited nearly identical Z_spec and very similar MTRasym curves. Additionally, rFOV with a 1.5 mm×1.5 mm in-plane resolution could be achieved in approximately 3 min. rFOV method displayed better structural details for the entire rectum, including CEST contrast maps and quantitative curves. ConclusionCEST MRI proves valuable in diagnosing rectal diseases, and employing the rFOV technique could provide higher spatial and temporal resolution. CEST MRI should be the preferred choice for offering improved diagnostic capabilities with its potential for rectal disease diagnosis.

Objective To investigate the inhibitory effect of Ginsenosides Rg1(GS-Rg1)on the proliferation and metastasis of tongue squamous cell carcinoma(TSCC),and its related mechanisms of action.Methods TSCC cells were treated with GS-Rg1 at concentrations of 1.25,2.5,5.0 and 10.0 μmol·L-1 for 48 hours.The proliferation ability of cells at different concentrations was measured by cell counting kit-8(CCK-8)experiment,and the IC5ovalue of GS-Rg1 at CAL-27 for 48 hours was calculated.TSCC cells CAL-27 were divided into control group and GS-Rg1 group.The control group and GS-Rg1 group were treated with 0.9％NaCl and IC50concentration of GS-Rg1 for 48 hours,respectively.The cell cycle distribution of each group was detected by flow cytometry,and the cell metastasis ability of each group was detected by Transwell experiment.Construct TOP/FOP Flash plasmid,transfect control group and GS-Rg1 group,and detect the effect of GS-Rg1 effect on wnt/β-catenin signaling pathway activity in TSCC cell CAL-27 using luciferase assay.Using wnt/β-catenin pathway inhibitor XAV939 treated GS-Rg1 group cells(XAV939+GS-Rg1 group),and wnt/β-catenin pathway activator HLY78 was used to treat GS-Rg1 group cells(HLY78+GS-Rg1 group)and detect changes of wnt/β-catenin signaling pathway activity,the cell proliferation ability,cell cycle distribution,and metastasis ability in XAV939+GS-Rg1 group,HLY78+GS-Rg1 group and GS-Rg1 group.The expression of wnt/β-catenin signaling pathway related proteins β-catenin,and its downstream cell cycle related proteins cellular myelocytomatosis oncogene(cMYC),Cyclin dependent kinase 4(CDK4),andcyclinD1,as well as metastasis related proteins E-cadherin,N-cadherin and matrix metalloproteinase 2(MMP-2)were detected by Western blotting in each group of cells.Results GS-Rg1 significantly inhibited the proliferation ability of TSCC cells CAL-27(P＜0.05),and the IC50value of GS-Rg1 on CAL-27 was(5.46±1.58)μmol·L-1.The ratio of GO/G1 phase cells in the control group and GS-Rg1 group were(60.65±2.16)％and(71.20±2.38)％,respectively;the number of cell transmembrane penetration were 87.33±7.51 and 50.67±3.21,respectively;the luciferase activity were 1.00±0.02 and 0.35±0.06,respectively.Compared with the control group,the GS-Rg1 group showed cell cycle arrest in GO/G1 phase,decreased cell metastasis ability,and the activity of wnt/β-catenin signaling pathway decreased(P＜0.05,P＜0.01).Compared with the GS-Rg1 group,the activity of the wnt/β-catenin signaling pathway was decreased,cell proliferation ability and metastasis ability was decreased(P＜0.05),while the number of GO/G1 phase cells was increased(P＜0.05),the expression of β-catenin,cMYC,CDK4,cyclinD1,E-cadherin and MMP-2 proteins were decreased(P＜0.05),while the expression of N-cadherin protein increased in XAV939+GS-Rg1 group cells.However,the result were opposite in the HLY78+GS-Rg1 group of cells.Conclusion GS-Rg1 downregulates wnt/β-catenin signaling pathway inhibits the proliferation and metastasis ability of TSCC cells.

Objective To investigate the efficacy and safety of intensity-modulated radiation therapy combined with camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods A total of 84 patients with advanced HCC admitted to our hospital from January to December 2020 were selected as the study objects,and were randomly divided into the observation group and the control group,with 42 cases in each group.Patients in the observation group received intensity-modulated radiation therapy combined with carrelli-zumab,and patients in the control group received intensity-modulated radiation therapy.The short-term efficacy,immune function and long-term survival rate of patietns in the two groups were compared,and the incidence of adverse reactions was recorded.Results The total effec-tive rates of the observation group 1 month and 3 months after treatment were significantly higher than those of the control group(P<0.05).The levels of CD3+,CD4+ and CD4+/CD8+ 1 month and 3 months after treatment were all increased in the two groups,while the levels of CD8+ in both two groups were decreased(P<0.05),and the levels of CD3+,CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group(P<0.05),and the levels of CD8+ in the observation group were lower than those in the control group(P<0.05).The median survival time of patients in the observation group was significantly longer than that of patients in the control group(P<0.05).The incidence of cutaneous capillary hyperplasia in the observation group was higher than that in the control group(P<0.001),and there was no significant difference in the incidence of other adverse reactions between the two groups(P>0.05),and all of adverse reactions were grades 1 to 2.Conclusion Intensity-modulated radiation therapy combined with camrelizumab has a good effect on HCC,it can improve the immune function of the body,and control the development of the disease,with good safety.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.