Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective:To design a remote monitoring and early warning system of ventilators,so as to adapt to data collection for different types of ventilators,and achieve early warning for abnormal status in operation data of ventilators.Methods:A three-layer structure,which used information gateway of Internet of Things(IoTs)with multi communication standard as the core,and integrated with multiple interfaces,was adopted to construct a remote monitoring and early warning system of ventilators.Boolean function was used to determine strings of incorrect data,and extract respiratory information.Using incremental isolated forest algorithm processed ventilators'operation data for realizing anomaly detection.And then,the detection results were presented through a display module,so as to conduct early warning for existing abnormal situations.Results:The remote monitoring and early warning system of ventilator had an accuracy rate of monitoring over 98.0%for abnormity of different types of ventilators,which timely warning rate was over 98.5%.Conclusion:The designed remote monitoring and early warning system of ventilator can provide clear results of remote monitoring and early warning of ventilator,which can timely find abnormal status,and effectively improve management efficiency for ventilator,and promote the intelligent development of medical treatment.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Objective:To design a remote monitoring and early warning system of ventilators,so as to adapt to data collection for different types of ventilators,and achieve early warning for abnormal status in operation data of ventilators.Methods:A three-layer structure,which used information gateway of Internet of Things(IoTs)with multi communication standard as the core,and integrated with multiple interfaces,was adopted to construct a remote monitoring and early warning system of ventilators.Boolean function was used to determine strings of incorrect data,and extract respiratory information.Using incremental isolated forest algorithm processed ventilators'operation data for realizing anomaly detection.And then,the detection results were presented through a display module,so as to conduct early warning for existing abnormal situations.Results:The remote monitoring and early warning system of ventilator had an accuracy rate of monitoring over 98.0%for abnormity of different types of ventilators,which timely warning rate was over 98.5%.Conclusion:The designed remote monitoring and early warning system of ventilator can provide clear results of remote monitoring and early warning of ventilator,which can timely find abnormal status,and effectively improve management efficiency for ventilator,and promote the intelligent development of medical treatment.

Objective To investigate the effect of Sclareol(SCL)on LX-2 hepatic stellate cell activation and CCl4-induced liver fibrosis in mice,and to further explore its mechanism.Methods A total of 40 Kunming mice were randomly divided into healthy group,model group(10%CCl4)and SCL administration group,and silybin positive control group(10%CCl4+100 mg·kg-1 Silybin),and SCL administration group was divided into low SCL(10%CCl4+20 mg·kg-1 SCL)and high dose group(10%CCl4+40 mg·kg-1 SCL).Mice in all groups were intraperitoneally injected with 10%olive oil-diluted CCl4 three times a week for four weeks,except for the healthy group.Starting from the third week,the dosing group was given different doses of SCL by gavage daily,and the positive control group was given silybin daily,and the mice were sacrificed and serum and liver tissue were collected after four weeks.In whole animal experiments,biochemical kits were used to detect the changes in the serum levels of glutamate aminotransferase(ALT)and aspartate aminotransferase(AST)in mice with liver fibrosis.Hematoxylin-eosin(HE),Sirius Red and Masson staining were used to detect microstructural changes and collagen deposition in liver tissues.Immunohistochemistry was used to detect the expression of fibrosis marker proteins α-smooth muscle actin(α-SMA)and fibrous collagen I.in liver tissues.In vitro,LX-2 human hepatic stellate cells were used for normal culture in the blank group,and the activation of LX-2 hepatic stellate cells was induced by transforming growth factor-β1(TGF-β1)in the model group,and the SCL administration group was divided into SCL low-dose group(5 ng·mL-1 TGF-β1+10 μmol·L-1 SCL)and high-dose group(5 ng·mL-1 TGF-β1+20 μmol·L-1 SCL).Subsequently,Transwell and EdU assays were used to detect the effects of SCL on the migration and proliferation of LX-2 cells.The expression of fibrosis marker proteins α-SMA and Collagen I.affected by SCL was detected by immunofluorescence.Western blot was used to detect the expression of related proteins in TGF-β/Smad pathway.Results In animal experiments,compared with the model group,SCL could significantly improve the liver function indexes and liver histopathological changes in liver fibrosis model mice.In addition,in vitro cell experiments,compared with the model group,SCL can effectively inhibit the migration and proliferation of hepatic stellate cells and inhibit their activation.Further studies showed that compared with the model group,SCL significantly up-regulated the expression of Smad7 protein and significantly down-regulated the phosphorylation levels of Smad2 and Smad3 proteins.Conclusion SCL has a significant alleviating effect on CCl4-induced liver fibrosis and TGF-β1-induced LX-2 activation in mice,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

To investigate the effects of ORF9 gene of porcine circovirus type 2(PCV2)on PK-15,eu-karyotic expression plasmid was constructed and transfected into PK-15 cells,and the effects of overexpression of ORF9 on proliferation,apoptosis and immunization of PK-15 cells were exam-ined by flow cytometry and qRT-PCR.The results showed that ORF9 gene overexpression signifi-cantly up-regulated the expression levels of the ER stress marker gene GRP78,increased the num-ber of S phase cells,accelerated cell cycle progression,increased the apoptosis rate of PK-15 cells,up-regulated the expression levels of apoptosis-related genes caspase-3,caspase-8,caspase-9,p53 and Bax(P＜0.01),down-regulated the expression levels of apoptosis-related genes Bcl-2,up-reg-ulated the expression levels of immune-related genes 1L-8,IL-10,NF-κB and TNF-α(P＜0.01),and down-regulated the expression levels of immune-related genes IL-2,IFN-β and IL-12(P＜0.01).The above results indicate that ORF9 gene may promote the proliferation and apoptosis of PK-15 cells and play a role in the escape process of PK-15 cells.

In order to understand the genomic characteristics and genetic variation and strain type of infectious bursal disease virus(IBDV)isolate GZGY2022,which caused the death of chickens in Guizhou farm,primers were designed to amplify the whole genome of the isolate,and genetic evo-lution and strain type analysis were performed after cloning and sequencing.The results showed that the A and B segments of IBDV genome were 3 260,2 827 bp,respectively,encoding VP2-VP5 and VP1 genes.The nucleotide sequence homology between the A and B segments of this strain and the VvIBDV were 96.2％-98.7％and 87.7％-98.9％,respectively,which is the highest with NN1172 strain,83.1％-94.7％and 90.1％-91.0％with other strains.The results of genetic evolution and strain type study showed that IBDV strains can be divided into 6 branches according to antigen and virulence,and the A and B segments of the strain were clustered in the evolutionary branch of VvIBDV,and the strain was A3B3 genotype according to the new genotype classification method.The results of amino acid sequence analysis showed that there were 3 and 7 unique amino acid site variations in the A and B segments of the strain,respectively,and 13 unique characteristic amino acid sites in the coding region of the full-length genome were consistent with VvIBDV.The VP2 sequence of segment A has 19 characteristic amino acid identical with VvIBDV,among which hyper variable regions 222A,242I,253Q,256I,279D,284A,294I and 299S were characteristic ami-no acid sites of the VvIBDV,and the heptapeptide region sequence SWSASGS was consistent with the virulent strain.The VP1 sequence of segment B has 10 characteristic amino acid identical with VvIBDV,among which 61I,145T and 287A were the characteristic amino acid sites of the VvIB-DV.In addition,the nucleotide sequence GGTGCC of 777-782 did not form the restriction endo-nuclease site of Kpn Ⅰ,and combined with the triplet site 145/146/147(TEG),the segment B was consistent with the NN1172 strain,showed that its virulence was slightly weaker than that of the B2 strain of VvIBDV.The results of recombination analysis showed that there were no breaks and recombination sites in the sequence of the strain,and no recombination event occurred.In summa-ry,this study found that GZGY2022 strain belonged to the A3B3 genotype non-recombinant VvIB-DV strain,and its special amino acid sites were consistent with the molecular characteristics of VvIBDV.This study lays the foundation for further exploring the genomic characteristics and path-ogenicity of VvIBDV.

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

Objective To construct a machine learning prediction model for postoperative liver injury in patients with non-liver surgery based on preoperative and intraoperative medication indicators.Methods A case-control study was conducted on 315 patients with liver injury after non-liver surgery selected from the databases developed by 3 large general hospitals from January 2014 to September 2022.With the positive/negative ratio of 1 ∶3,928 cases in corresponding period with non-liver surgery and without liver injury were randomly matched as negative control cases.These 1243 patients were randomly divided into the modeling group(n=869)and the validation group(n=374)in a ratio of 7∶3 using the R language setting code.Preoperative clinical indicators(basic information,medical history,relevant scale score,surgical information and results of laboratory tests)and intraoperative medication were used to construct the prediction model for liver injury after non-liver surgery based on 4 machine learning algorithms,k-nearest neighbor(KNN),support vector machine linear(SVM),logic regression(LR)and extreme gradient boosting(XGBoost).In the validation group,receiver operating characteristic(ROC)curve,precision-recall curve(P-R),decision curve analysis(DCA)curve,Kappa value,sensitivity,specificity,Brier score,and F1 score were applied to evaluate the efficacy of model.Results The model established by 4 machine learning algorithms to predict postoperative liver injury after non-liver surgery was optimal using the XGBoost algorithm.The area under the receiver operating characteristic curve(AUROC)was 0.916(95%CI:0.883～0.949),area under the precision-recall curve(AUPRC)was 0.841,Brier score was 0.097,and sensitivity and specificity was 78.95%and 87.10%,respectively.Conclusion The postoperative liver injury prediction model for non-liver surgery based on the XGBoost algorithm has effective prediction for the occurrence of postoperative liver injury.

Objective To investigate the effect of Sclareol(SCL)on LX-2 hepatic stellate cell activation and CCl4-induced liver fibrosis in mice,and to further explore its mechanism.Methods A total of 40 Kunming mice were randomly divided into healthy group,model group(10%CCl4)and SCL administration group,and silybin positive control group(10%CCl4+100 mg·kg-1 Silybin),and SCL administration group was divided into low SCL(10%CCl4+20 mg·kg-1 SCL)and high dose group(10%CCl4+40 mg·kg-1 SCL).Mice in all groups were intraperitoneally injected with 10%olive oil-diluted CCl4 three times a week for four weeks,except for the healthy group.Starting from the third week,the dosing group was given different doses of SCL by gavage daily,and the positive control group was given silybin daily,and the mice were sacrificed and serum and liver tissue were collected after four weeks.In whole animal experiments,biochemical kits were used to detect the changes in the serum levels of glutamate aminotransferase(ALT)and aspartate aminotransferase(AST)in mice with liver fibrosis.Hematoxylin-eosin(HE),Sirius Red and Masson staining were used to detect microstructural changes and collagen deposition in liver tissues.Immunohistochemistry was used to detect the expression of fibrosis marker proteins α-smooth muscle actin(α-SMA)and fibrous collagen I.in liver tissues.In vitro,LX-2 human hepatic stellate cells were used for normal culture in the blank group,and the activation of LX-2 hepatic stellate cells was induced by transforming growth factor-β1(TGF-β1)in the model group,and the SCL administration group was divided into SCL low-dose group(5 ng·mL-1 TGF-β1+10 μmol·L-1 SCL)and high-dose group(5 ng·mL-1 TGF-β1+20 μmol·L-1 SCL).Subsequently,Transwell and EdU assays were used to detect the effects of SCL on the migration and proliferation of LX-2 cells.The expression of fibrosis marker proteins α-SMA and Collagen I.affected by SCL was detected by immunofluorescence.Western blot was used to detect the expression of related proteins in TGF-β/Smad pathway.Results In animal experiments,compared with the model group,SCL could significantly improve the liver function indexes and liver histopathological changes in liver fibrosis model mice.In addition,in vitro cell experiments,compared with the model group,SCL can effectively inhibit the migration and proliferation of hepatic stellate cells and inhibit their activation.Further studies showed that compared with the model group,SCL significantly up-regulated the expression of Smad7 protein and significantly down-regulated the phosphorylation levels of Smad2 and Smad3 proteins.Conclusion SCL has a significant alleviating effect on CCl4-induced liver fibrosis and TGF-β1-induced LX-2 activation in mice,and the mechanism may be related to the regulation of TGF-β/Smad pathway.