ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

The red doctor spirit is the advanced culture of the Communist Party of China formed under a specific historical and cultural background. It can be summarized as “political firmness， excellent technology， working hard， and healing the wounded and rescuing the dying.” This content has many hidden similarities and integrations with the goal of cultivating humanistic literacy for medical students in military medical universities. This paper aimed to identify the important connection points between the red doctor spirit and the contents and goals of medical humanities teaching， as well as integrate the red doctor spirit into medical humanities teaching by various dimensions， including systematic reconstruction of textbook content， immersive innovation in teaching form， three-dimensional support in resource construction， and innovative implementation of narrative medicine teaching. It also further explored the extension of the red doctor spirit in military medical humanistic literacy， namely， revolutionary humanism and revolutionary heroism， thereby enhancing the effectiveness of medical humanistic teaching.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

Objective To explore the effects of polystyrene microplastics(PS-MPs)on the growth,activity,oxida-tive stress levels,biofilm formation and virulence of Klebsiella pneumoniae.Methods Klebsiella pneumoniae was exposed to PS-MPs at different concentrations(10,50 and 100 μg/ml)and particle sizes(0.1,1.0 and 5.0 μm),and the growth curves were measured.The bacterial activity was determined by CCK-8(cell counting kit-8).The level of intracellular reactive oxygen species(ROS)was determined by fluorescence probe.The biofilm forming ability was determined by crystal violet staining.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the relative expression levels of biofilm-forming genes(luxS,mrkA,wbbM,pgaA,wzm)and viru-lence genes(ureA,uge,wabG,fimH).Results A high concentration(100 μg/ml)of 0.1 μm PS-MPs had a stronger inhibitory effect on the growth and activity of Klebsiella pneumoniae,and the intracellular ROS level signifi-cantly increased,indicating that smaller particle size and higher concentration of PS-MPs were more toxic to bacte-ria.PS-MPs of 100 μg/ml particle size groups(0.1,1.0 and 5.0 μm)significantly promoted the biofilm forma-tion of Klebsiella pneumoniae.The relative expression levels of biofilm formation related genes(luxS,mrkA,wbbM,pgaA,wzm)and virulence genes(ureA,uge,wabG,fimH)increased.Conclusion By inducing Kleb-siella pneumoniae to produce a high level of ROS,PS-MPs can cause oxidative stress,inhibit the growth and activi-ty of bacteria,and enhance the biofilm formation ability and virulence,thus affecting the biological characteristics of Klebsiae pneumoniae.

ObjectiveTo monitor and analyze the epidemiological characteristics of viral pathogens among elderly patients with acute upper respiratory tract infections in Shaoxing City from 2020 to 2023, to guide prevention and treatment. MethodsNasopharyngeal swab samples were collected from elderly patients at the Infectious Disease Outpatient Department of Shaoxing infectious disease surveillance sentinel hospital for acute upper respiratory tract infections between January 2020 and December 2023. The multiple nucleic acid detection method was used to detect the influenza A virus (Flu A), influenza B virus (Flu B), respiratory syncytial virus (RSV), human rhinovirus (HRV), adenoviruses (ADV), and Mycoplasma pneumoniae (MP). Epidemiological analysis was conducted on the six pathogens mentioned above. χ2 test was used for statistical analysis. ResultsOf the 3 670 nasopharyngeal swab samples collected from the elderly patients with acute upper respiratory tract infections aged 60-89,2 330 were positive, with a detection rate of 63.49%. Among these, 2 293 were single pathogen infections, including 1 255 Flu A, 356 Flu B, 63 ADV, 76 RSV, 363 HRV, and 180 MP cases, with positive rates of 34.20%, 9.70%, 1.72%, 2.07%, 9.89%, and 4.90%, respectively. A total of 37 cases were mixed infections with two or more pathogens, with a positive detection rate of 1.01%. The rate of severe cases was significantly higher in patients with mixed infections compared to single pathogen infections (χ2=24.468, P<0.001). Among the single pathogen infections, ADV had the highest rate of severe cases at 4.76%, followed by Flu A at 3.19% and RSV at 2.63%. The lowest rate of severe cases was caused by MP infection at 0.56%. The distribution of severe cases of the six respiratory pathogen infections corresponded to their epidemic peaks. ConclusionAcute upper respiratory tract infections in the elderly are closely related to different respiratory pathogens, and mixed respiratory pathogen infections may increase the severity of respiratory cases in elderly patients.

Objective:To explore the effect and possible mechanism of Zexie Tang(ZXT)regulate the balance of M1/M2 polarization in macrophage cells.Methods:Lipid metabolism disorder mouse model was induced by Western diet(WD)in vivo,RAW264.7 cell M1/M2 macrophage model was induced by LPS/IL-4 in vitro,set up blank group,model group and ZXT group.The flu-orescence intensity of M1 and M2 macrophage markers in adipose tissue and RAW264.7 cells was observed by immunofluorescence staining;protein levels of p-AKT,AKT and COX-2 were measured by Western blot;levels of macrophage marker gene mRNAs of M1 and M2 were analysed by qPCR;IL-1β and IL-10 were measured by ELISA;content of NO was detected by Griess;binding of active components of Alismatis Rhizoma and Atractylodes Macrocephala with PI3K protein was analyzed by Docking.Results:Compared with WD group,expression of CD11c was significantly decreased in ZXT group,while expression of CD206 was significantly up-regulated;ZXT reversed LPS-induced increased in CD80 expression,down-regulated mRNA levels of M1 macrophage marker gene iNOS,etc,decreased the expression of COX-2 protein,and inhibited the secretion of IL-1β(P<0.001);ZXT promoted IL-4-induced CD206 expression,up-regulation of M2 macrophage marker gene Arg-1 and other mRNAs levels and secretion of IL-10;ZXT reversed the LPS-induced increased in NO release;p-AKT/AKT protein level increased in vivo and in vitro after ZXT administration;Docking re-sults show that many active ingredients in Alismatis Rhizoma and Atractylodes Macrocephala could form hydrogen bonds stably with PI3K protein.Conclusion:ZXT regulates the M1/M2 polarization balance of macrophages,and its mechanism may be related to the regulation of PI3K/AKT pathway.

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

Objective:To investigate the clinical value of magnetic resonance imaging (MRI) based integrated deep learning model for predicting the times of linear staplers used in double stapling technique for middle-low rectal cancer resection.Methods:The retrospective cohort study was conducted. The clinicopathological data of 263 patients who underwent low anterior resection (LAR) for middle-low rectal cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from January 2018 to December 2022 were collected as training dataset. There were 183 males and 80 females, aged 63(55,68)years. The clinicopathological data of 128 patients with middle-low rectal cancer were collected as validation dataset, including 83 males and 45 females, with age as 65(57,70)years. The training dataset was used to construct the prediction model, and the validation dataset was used to validate the prediction model. Observation indicators: (1) clinicopathological features of patients in the training dataset; (2) influencing factors for ≥3 times using of linear staplers in the operation; (3) prediction model construction; (4) efficiency evaluation of prediction model; (5) validation of prediction model. Measurement data with skewed distribution were represented as M( Q1, Q3), and Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Wilcoxon rank sum test was used for non-parametric data analysis. Univariate analysis was conducted using the Logistic regression model, and multivariate analysis was conducted using the Logistic stepwise regression model. The receiver operating characteristic (ROC) curve was draw and the area under the curve (AUC) was calculated. The AUC of the ROC curve >0.75 indicated the prediction model as acceptable. Comparison of AUC was conducted using the Delong test. Results:(1) Clinicopathological features of patients in the training dataset. Of the 263 patients, there were 48 cases with linear staplers used in the operation ≥3 times and 215 cases with linear staplers used in the operation ≤2 times. Cases with preoperative serum carcinoembryonic antigen (CEA) >5 μg/L, cases with anastomotic leakage, cases with tumor diameter ≥5 cm were 20, 12, 13 in the 48 cases with linear staplers used ≥3 times in the operation, versus 56, 26, 21 in the 215 cases with linear staplers used ≤2 times in the operation, showing significant differences in the above indicators between them ( χ2=4.66, 5.29, 10.45, P<0.05). (2) Influencing factors for ≥3 times using of linear staplers in the operation. Results of multivariate analysis showed that preoperative serum CEA >5 μg/L and tumor diameter ≥5 cm were independent risk factors for ≥3 times using of linear staplers in the operation ( odds ratio=2.26, 3.39, 95% confidence interval as 1.15-4.43, 1.50-7.65, P<0.05). (3) Prediction model construction. According to the results of multivariate analysis, the clinical prediction model was established as Logit(P)=-2.018+0.814×preoperative serum CEA (>5 μg/L as 1, ≤5 μg/L as 0)+ 1.222×tumor diameter (≥5 cm as 1, <5 cm as 0). The image data segmented by the Mask region convolutional neural network (MASK R-CNN) was input into the three-dimensional convolutional neural network (C3D), and the image prediction model was constructed by training. The image data segmented by the MASK R-CNN and the clinical independent risk factors were input into the C3D, and the integrated prediction model was constructed by training. (4) Efficiency evaluation of prediction model. The sensitivity, specificity and accuracy of the clinical prediction model was 70.0%, 81.0% and 79.4%, respectively, with the Yoden index as 0.51. The sensitivity, specificity and accuracy of the image prediction model was 50.0%, 98.3% and 91.2%, respectively, with the Yoden index as 0.48. The sensitivity, specificity and accuracy of the integrated prediction model was 70.0%, 98.3% and 94.1%, respectively, with the Yoden index as 0.68. The AUC of clinical prediction model, image prediction model and integrated prediction model was 0.72(95% confidence interval as 0.61-0.83), 0.81(95% confidence interval as 0.71-0.91) and 0.88(95% confidence interval as 0.81-0.95), respectively. There were significant differences in the efficacy between the integrated prediction model and the image prediction model or the clinical prediction model ( Z=2.98, 2.48, P<0.05). (5) Validation of prediction model. The three prediction models were externally validated by validation dataset. The sensitivity, specificity and accuracy of the clinical prediction model was 62.5%, 66.1% and 65.6%, respectively, with the Yoden index as 0.29. The sensitivity, specificity and accuracy of the image prediction model was 58.8%, 95.5% and 92.1%, respectively, with the Yoden index as 0.64. The sensitivity, specificity and accuracy of the integrated prediction model was 68.8%, 97.3% and 93.8%, respectively, with the Yoden index as 0.66. The AUC of clinical prediction model, image prediction model and integrated prediction model was 0.65(95% confidence interval as 0.55-0.75), 0.75(95% confidence interval as 0.66-0.84) and 0.84(95% confidence interval as 0.74-0.93), respec-tively. There was significant differences in the efficacy between the clinical prediction model and the integrated prediction model ( Z=3.24, P<0.05). Conclusion:The MRI-based deep-learning model can help predicting the high-risk population with ≥3 times using of linear staplers in resection of middle-low rectal cancer with double stapling technique.