ObjectiveTo observe the effect of the combination of total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium on reversal cholesterol transport （RCT） in hyperlipidemia rats， and to discuss its mechanism. MethodSixty SD rats were randomly divided into control group， high-fat diet group， total saponin of Astragali Radix-total alkaloids of Nelumbinis Folium low （17 mg·kg^-1+40 mg·kg^-1）， middle （34 mg·kg^-1+80 mg·kg^-1）， high dose （68 mg·kg^-1+160 mg·kg^-1） groups and simvastatin （2.1 mg·kg^-1） group， with 10 mice in each group. The Hyperlipidemia model was duplicated by feeding rats with a high-fat diet for 6 weeks. From the 3rd week， except for the control group and the high-fat diet group given distilled water， other groups were given corresponding drugs intragastric treatment for 4 weeks. The changes in blood lipid and liver function of rats were detected by an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to observe the pathological morphological changes and steatosis of rat liver tissue. The contents of total cholesterol （TC） and total bile acid （TBA） in rat liver tissue and feces were determined by a semi-automatic biochemical analyzer. The mRNA and protein expression levels of peroxisome proliferators-activated receptors γ （PPARγ）， liver X receptors α （LXRα）， ATP-binding cassette transporter G1 （ABCG1） and cholesterol 7α-hydroxylase （CYP7A1） in rat liver tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the contents or activities of TC， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， TBA， aspartate aminotransferase （AST）， alanine aminotransferase （ALT） in serum were significantly increased （P<0.01）， and the contents of high-density lipoprotein cholesterol （HDL-C） in the high-fat diet group were significantly decreased （P<0.01）. The hepatocyte was clearly swollen like ballooning degeneration， with a lot of fat vacuoles and red fat droplets. The contents of TC and TBA in liver tissue and feces were significantly increased （P<0.01）， and the mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly decreased （P<0.01）. Compared with the high-fat diet group， the contents or activities of TC， TG， LDL-C， TBA， AST， and ALT in the serum of rats in administered groups were significantly decreased （P<0.01）， while the content of HDL-C was significantly increased （P<0.01）. Hepatocyte swelling was significantly reduced， and the ballooning degeneration， fat vacuoles， and red lipid droplets in liver tissue were significantly decreased. The contents of TC and TBA in liver tissue were significantly decreased （P<0.05， P<0.01）， and the contents of TC and TBA in feces were significantly increased （P<0.05， P<0.01）. The mRNA and protein expression levels of PPARγ， LXRα， ABCG1， and CYP7A1 in liver tissue were significantly increased （P<0.05， P<0.01）. ConclusionTotal saponin of Astragali Radix-total alkaloids of Nelumbinis Folium has a positive effect on the prevention and treatment of hyperlipidemia rats， and its mechanism may be related to the activation of PPARγ/LXRα/ABCG1 signaling pathway and regulation of RCT.

OBJECTIVE To explore the improving effect of luteolin （Lut） on placental dysfunction in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on hedgehog （Hh） signaling pathway. METHODS Twenty female rats were randomly selected as a control group and fed a normal diet. The remaining female rats were fed a high-fat and high-sugar diet for 8 weeks and then caged with male rats. Pregnant rats were administered 35 mg/kg streptozotocin intraperitoneally to establish GDM models. Successfully modeled female rats were randomly allocated to model group， SAG group （Hh signaling pathway activator SAG 50 mg/kg）， Lut low-dose group （Lut 40 mg/kg）， Lut high-dose group （Lut 80 mg/kg）， and Lut high+ITR group （Lut 80 mg/kg+Hh signaling pathway antagonist itraconazole 50 mg/kg）， with 20 rats in each group. Female rats in each drug group were intubated with the corresponding drug solution once a day for 19 days. After the final administration， the serum glucose- fat metabolic parameters （levels of fasting blood glucose and fasting insulin， insulin resistance index）， placental quality， placental permeability [Evan’s blue （EB） content]， and pathological changes in placental tissue were observed. The activities of superoxide dismutase （SOD）， the contents of malondialdehyde （MDA） and reduced glutathione （GSH）， and the protein expressions of Sonic Hh （Shh）， Patched-1 （Ptch1）， Smoothened （Smo） and Gli family zinc finger-1 （Gli1） in placental tissue were detected. HBB_ RESULTS Compared with the control group， rats in the model group showed narrow capillary lumens， perivascular fibrosis in placental tissue， and a significant increase in serum glucose-fat metabolic parameters， placental quality， contents of EB and MDA， while there was a significant decrease in SOD activity， GSH content， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）. Compared with the model group， rats in the SAG group， Lut low-dose and high-dose groups had widened capillary lumens， a significant decrease in perivascular fibrosis in placental tissue， serum glucose-fat metabolic parameters， placental qualities， EB and MDA contents， while there was a significant increase in SOD activities， GSH contents， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）， with the high-dose group showing no significant difference compared to the SAG group （P＞0.05）. The Hh signaling pathway antagonist itraconazole could significantly reverse the improving effects of Lut on the above indicators （P＜0.05）. CONCLUSIONS Lut can improve glucose metabolism parameters of GDM rats， reduce placental permeability， alleviate pathological damage to placental tissue， and reduce oxidative stress. These effects may be related to the activation of the Hh signaling pathway.

Objective Liver cancer is the second leading cause of tumor-related death.The efficacy of local thermal ablation is comparable to surgical resection for the early hepatocellular carcinoma(HCC),and the ablation technique is minimally invasive,repeatable,and has a low complication rate.However,early recurrence((2 years)is the main cause of death after HCC ablation,but there is still a lack of accurate and reliable prediction models for early recurrence.Therefore,this survey intended to construct prediction models for early recurrence of HCC after ablation by using preoperative gadoxetic acid disodium-enhanced magnetic resonance(MR)images data combined with radiomics methods,evaluate and verify their predictive efficacy.To explore the application value of contrast-enhanced MRI imaging before ablation in the prognosis assessment of HCC patients,and to provide reliable data and theoretical basis for clinical treatment decisions.Methods A retrospective study was performed on 120 patients with HCC who underwent ablation and all the patients were underwent contrast-enhanced MRI examination within 1 month.A total of 1318 radiomic features were extracted from each patient by using preoperative T2-weighted sequence(T2WI)images of contrast-enhanced MRI.After feature selection,six machine learning algorithms would be used for construction of models and comparison.Finally,Logistic regression analysis was used to establish a clinical model,a radiomics model and a combined model which included the above risk factors and radiologic features.The nomogram was constructed based the combined model to evaluate the differentiation,accuracy and clinical benefit.Results Five radiomic features most closely related to early recurrence were identified and selected for model construction.The radiomic model had effective predictive performance,with AUC of 0.80 in the training sets.Two clinical risk factors associated with early recurrence,including tumor number and peritumoral hypodensity on the hepatobiliary phase,were selected to established a clinical-radiological-radiomics(CRRM)model,with AUC as high as 0.92 in the validation sets.The nomogram of CRRM model was constructed and the calibration curves indicated the goodness of fit.Decision curve analysis further confirmed the clinical usefulness of CRRM model.Conclusion The radiomics model of preoperatively contrast-enhanced MRI-T2WI image features was identified be effective to predict HCC early recurrence.In contrast,the CRRM model could be used as a more comprehensive and superior tool to predict individual probability of early recurrence.Patients at high risk of early recurrence could be identified and the appropriate and effective preoperative treatments could also be taken,to improve the prognosis and long-term survival rate of HCC patients the individualized treatment strategies should be formulated.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objective:Based on bioinformatics,new immune-related LncRNAs related to the prognosis of gastric cancer were screened,and a prognostic risk model of immune-related LncRNA was further constructed,in order to be used as a new indicator for early diagnosis and prognostic status of gastric cancer.Methods:The gastric cancer transcriptome data and corresponding clinical prog-nosis data were downloaded from multiple data platforms,and the immune-related LncRNAs of gastric cancer were screened by bioin-formatics methods.Cox regression analysis was used to screen LncRNAs related to immune prognosis in gastric cancer,and LncRNAs related to immune prognosis with independent prognostic significance were identified to construct a prognostic risk model,and the risk score of each patient was calculated.Patients were divided into low-risk and high-risk groups according to the cutpoint.Kaplan-Meier analysis was performed for survival analysis and survival curves were drawn,nomograms were drawn and internal validation was per-formed,and univariate and multivariate Cox regression analysis was performed to analyze the relationship between risk scores and clin-icopathological characteristics and survival prognosis of gastric cancer patients.Results:Three immune prognosis-related LncRNAs(UCA1,MIR4435-1HG,RP11-617F23.1)were identified by Cox regression analysis,and a predictive scoring model was constructed to divide the patients into high-risk group and low-risk group according to the prognosis score.There was a statistically significant dif-ference in the prognosis of patients between the two groups(P<0.05).The multivariate Cox regression analysis risk score was an inde-pendent risk factor for the prognosis of gastric cancer,and the internal verification of the nomogram showed good reliability.Conclu-sion:Three immune-related LncRNAs in gastric cancer are significantly correlated with the prognosis of gastric cancer patients,and the predictive scoring model constructed based on them can effectively predict the prognosis and can be used as their independent prog-nostic biomarkers.

ObjectiveTo explore the efficacy and mechanism of Danshen Zexie decoction in treating the rats with metabolic-associated fatty liver disease （MAFLD）. MethodSixty male SD rats were randomized into control group， model group， essentiale （polyene phosphatidylcholine capsules， 0.144 g·kg^-1） group， and low-， medium-， and high-dose Danshen Zexie decoction （1.16， 2.32， and 4.64 g·kg^-1， respectively） groups. The rat model of MAFLD was established with high fat diet， and 8-week therapy started at the induction of MAFLD. The serum levels of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST）， as well as the liver levels of TC， TG， free fatty acid （FFA）， superoxide dismutase （SOD）， glutathione （GSH）， and malondialdehyde （MDA）， were measured. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining and oil red O staining， and the steatosis score and oil red O staining area were calculated. The level of reactive oxygen species （ROS） in the liver was detected by immunofluorescence. The protein levels of adenosine monophosphate-activated protein kinase （AMPK）， p-AMPK， nuclear factor E₂-related factor 2 （Nrf2）， glutamate-cysteine ligase catalytic subunit （GCLC）， glutamate-cysteine ligase modifier subunit （GCLM）， and nicotinamide adenine dinucleotide phosphate： quinine oxidoreductase （NQO1） in the liver were determined by Western blot. ResultCompared with control group， the modeling of MAFLD elevated the levels of TC， TG， ALT， and AST in the serum and TC， TG， FFA， MDA， and ROS in the liver （P<0.01）， lowered the levels of SOD and GSH and down-regulated the protein levels of phosphorylation（p）-AMPK， Nrf2， GCLC， GCLM， and NQO1 in the liver （P<0.05， P<0.01）. Further， a large number of lipid droplet vacuoles and balloon-like lesions appeared in the hepatocytes， and the steatosis score and oil red O staining area increased in the model group （P<0.01）. Compared with model group， Danshen Zexie decoction lowered the levels of TC， TG， ALT， and AST in the serum and TC， TG， FFA， MDA， and ROS in the liver （P<0.01）， increased the levels of SOD and GSH and up-regulated the protein levels of p-AMPK， Nrf2， GCLC， GCLM， and NQO1 in the liver （P<0.05， P<0.01）. Moreover， the decoction alleviated the degree of liver steatosis （P<0.05， P<0.01）. ConclusionDanshen Zexie decoction protects against MAFLD by activating AMPK/Nrf2 signaling pathway and suppressing oxidative stress.

Pulmonary surfactant(PS)is a kind of phospholipid-protein complex, whose main function is to reduce the surface tension of alveoli.Exogenous PS replacement therapy has been widely used in the clinical treatment of respiratory distress syndrome(RDS)and other diseases.The clinical application methods include preventive or rescue treatment, invasive or minimally invasive treatment, intubation-surfactant-extubation(INSURE)technology and atomization treatment, etc.Nowadays, INSURE technology has been widely accepted in clinical application, and new non-invasive drug administration methods such as thin catheter, laryngeal mask airway and atomization are being studied or adopted.In this article, the progress of methodological research on clinical application of PS in newborns in recent years is reviewed.

Taking the course of Chinese traditional medicine as an example, this paper discusses the construction and implementation effect of online teaching mode from the following four aspects: online teaching curriculum design, teaching implementation, teaching effect evaluation, and teaching reflection, with a view to providing beneficial reference for the follow-up hybrid teaching and promoting the construction of hybrid first-class courses by summarizing the experience of online teaching.

Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.

Animals ; Antibodies, Neutralizing/biosynthesis* ; Antibodies, Viral/biosynthesis* ; Body Weight/immunology* ; COVID-19/virology* ; Disease Models, Animal ; Disease Progression ; Humans ; Immunohistochemistry ; Lung/virology* ; Male ; Mesocricetus ; Nasal Cavity/virology* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Severity of Illness Index ; Viral Load