Objective:To investigate the liver-protective effect of Peipi Shugan Decoction (PSD) in rats with liver fibrosis through network pharmacology and experimental animal models.Methods:TCMSP was used to retrieve the active components of Peipi Shugan Decoction, GeneCards database was used to obtain the liver fibrosis related targets, and Venny 2.1 was used to obtain the intersection targets. A protein-protein interaction (PPI) network was constructed using the STRING 12.0 database, and Go function and KEGG pathway enrichment analysis were performed through David database. A total of 60 male Sprague-Dawley (SD) rats were divided into two groups: a blank control group ( n=10) and a model establishment group ( n=50) with random number table method. Liver fibrosis models were induced in the model group by intraperitoneal injection of a 40% CCl?- olive oil solution. After successful modeling, the rats were randomly assigned to the following groups ( n=10 per group): model group, colchicine group, and Peipi Shugan Decoction low-, medium-, and high-dosage groups. The colchicine group received colchicine suspension at 0.2 ml/kg via intragastric administration. Peipi Shugan Decoction low-, medium-, and high-dosage groups were administered the decoction at dosages of 2.81, 5.63, and 11.25 g/kg, respectively. The blank control and model groups received an equal volume of normal saline. All treatments were administered once daily for 8 consecutive weeks. HE staining and Masson staining were used to observe the morphological changes of liver tissue and the deposition of collagen fibers. he levels of GPT, GOT and ALP were detected by automatic biochemical analyzer. The expressions of JAK2/STAT1 signaling pathway related proteins, α - smooth muscle actin (α-SMA) and Collagen Ⅰ in rat liver were detected by Western blot. The expression of α-SMA protein in liver tissue was detected by immunohistochemistry. The number and ratio of CD4 + T cells and CD8 + T cells in liver tissue were analyzed by flow cytometry. The levels of IL-6, IL-1β and TNF-α in serum were detected by ELISA. Results:A total of 94 active components were screened out from Peipi Shugan Decoction; the prediction analysis results revealed that this compound formula shared 122 common targets with liver fibrosis diseases; The top five core targets with degree values in the PPI network are AKT1, TNF, IL-6, TP53, and IL-1β. GO enrichment analysis further indicated that Peipi Shugan Decoction mainly achieved anti-liver fibrosis effects by regulating JAK2/STAT1 signaling pathway and other mechanisms. Compared with the model group, the colchicine group and Peipi Shugan Decoction low-, medium-, and high-dosage groups exhibited decreased serum levels of GPT, GOT, ALP, IL-6, TNF-α, and IL-1β ( P<0.05), as well as reduced expression of α-SMA in liver tissue ( P<0.05). Peipi Shugan Decoction medium- and high-dosage groups showed increased protein expression of p-STAT1/STAT1 in liver tissue ( P<0.05), while Peipi Shugan Decoction high-dosage group demonstrated decreased α-SMA protein expression ( P<0.05). Additionally, Peipi Shugan Decoction medium- and high-dosage groups exhibited reduced expressions of CD4 + and CD8 + ( P<0.05). Conclusions:Peipi Shugan Decoction has the characteristics of multi-component, multi-target and multi-pathway in the treatment of liver fibrosis. Its mechanism is mainly related to activating the JAK2/STAT1 signaling pathway, inhibiting cellular inflammatory responses and hindering the activation of hepatic stellate cells (HSC).

Objective To investigate the mechanism of astragaloside in treating hepatic fibrosis(HF).Methods HSC-T6 was divided into a blank group,astragaloside group,inhibitor group(using the Sirt1 inhibitor EX527),and astragaloside plus inhibitor group,Except for the blank group using 100 μmol·L-1 H2O2 to create a model of oxidative stress in HSC-T6,with 4 h of intervention in the modeling group,and 24 h of intervention in the modeling group,except for the modeling group.and Collagen 1 levels in cell supernatants;biochemical kit assay to determine oxidative stress-related indexes in cells;flow cytometry to detect the content of ROS in cells;immunofluorescence to detect the content ofα-SMA in cells;and real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR)and protein immunoblotting(Western blot)to detect SIRT1,NRF2,HO-1,α-SMA,Collagen1 mRNA and protein expression levels in each group of cells.Results Compared with the blank control group,the contents of α-SMA,Collagen1 and cellular MDA and ROS in the supernatants of HSC-T6 treated with H2O2 were significantly increased,whereas the contents of CAT and the activity of SOD in the cells were significantly decreased,the expression levels of mRNA and protein of Sirt1,Nrf2 and HO-1 in the cells were decreased,and the α-SMA,Collagen1 mRNA expression levels increased(P＜0.05);Compared with the model group,the contents of MDA and ROS in cells were significantly decreased,the CAT content and SOD activity were significantly increased,the expression levels of α-SMA and Collagen1 in the supernatant were decreased in the astragaloside Ⅳ group and astragaloside Ⅳ plus inhibitor group,the mRNA and protein expression levels of Sirt1,Nrf2 and HO-1 were increased,and the mRNA expression levels of α-SMA and Collagen1 were decreased(P＜0.05).Conclusion Astragaloside can attenuate HSC-T6 oxidative stress caused by H2O2 stimulation,reduce oxidative stress product production and collagen fiber deposition,thus achieving anti-HF,and its mechanism of action may be related to the regulation of the Sirt1/Nrf2/HO-1 signaling pathway.

Objective To observe the effect of shoulder-high head back-up position on airway ob-struction and hypoxia during fiberoptic bronchoscopy under non-intubated general anesthesia.Methods A total of 170 patients undergoing painless fiberoptic bronchoscopy,97 males and 73 females,aged 18-64 years,BMI 18.5-28.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were randomly divided into two groups by ran-dom number method:observation group(group D,n=84)and control group(group C,n=83).Group D adopted the shoulder-high head back-up position,and group C adopted the supine position.All the pa-tients received intravenous general anesthesia of propfol combined with sufentanil,and were oxygenated via an ordinary endoscopic mask with an oxygen flow rate of 8-10 L/min.Fiberoptic bronchoscopy was per-formed when the modified observer assessment of alertness and sedation(MOAA/S)score was≤1 point.The number of cases in which hypoxia occurred and corrective measures were taken were recorded.The changes of HR,SBP,DBP,and SpO2 before induction of anesthesia(T1),1 minute after induction of an-esthesia(T2),endotracheal surface anesthesia(T3),at the time of examination(T4),and at the end of the examination(T5)were recorded.The degree of obstruction of the retropalatal space and retroglossal space at T2 were recorded.The level of glottic exposure and operating comfort of the endoscopist were recor-ded during the examination,and the incidence of postoperative neck discomfort,postoperative headache,postoperative dizziness,and nausea and vomiting were recorded.Results Compared with group C,the in-cidence of intraoperative moderate hypoxia,severe hypoxia,jaw support,and assisted ventilation was signifi-cantly decreased in group D(P＜0.05).Compared with T1,the HR were significantly increased at T3 and T4(P＜0.05),SBP and DBP were significantly decreased at T2,T4,and T5(P＜0.05),SpO2 was sig-nificantly increased at T2 and decreased at T4 in the two groups(P＜0.05),and SpO2 in group C was sig-nificantly decreased at T3(P＜0.05).Compared with group C,SpO2 was significantly increased at T4,the incidence of non-obstruction in the retrolingual space was significantly increased,and the incidence of com-plete obstruction in the retrolingual space was significantly decreased at T2,and the incidence of good glottic exposure was significantly increased,the incidence of poor glottic exposure was significantly decreased,and the incidence of good operating comfort of the endoscopist was significantly increased in group D(P＜0.05).There was no significant difference in the incidence of postoperative adverse events between the two groups.Conclusion Shoulder-high head back-up position can alleviate airway obstruction and reduce the incidence of hypoxia during fiberoptic bronchoscopy under non-intubated general anesthesia.

ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 （Nrf2）/heme oxygenase-1 （HO-1）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment， and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model， irbesartan （25 mg·kg^-1）， and high-， medium-， low-dose （33.8， 16.9， 8.45 g·kg^-1） Zhenwutang groups （n=15） and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed， and the traditional Chinese medicine （TCM） syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency， fasting blood glucose （FBG）， and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Nrf2， HO-1， glutamate-cysteine ligase catalytic subunit （GCLC）， and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group， the modeling increased the TCM syndrome score （P<0.05）， elevated the estradiol （E₂） and FBG levels （P<0.05）， lowered the testosterone （T）， triiodothyronine （T3）， and tetraiodothyronine （T4） levels （P<0.05）， and weakened the renal function （P<0.05）. In addition， the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening， decreased the catalase （CAT） activity， total antioxidant capacity （T-AOC）， and glutathione （GSH） content （P<0.05）， increased the malondialdehyde （MDA） content （P<0.05）， and down-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. Compared with the model group， high and medium doses of Zhenwutang decreased the TCM syndrome score and E₂ content （P<0.05）， increased the T， T3， and T4 content （P<0.05）， improved the renal function （P<0.05）， alleviated the pathological changes in the renal tissue， increased CAT， T-AOC， and GSH （P<0.05）， reduced MDA （P<0.05）， and up-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.

Objective To investigate the mechanism of astragaloside in treating hepatic fibrosis(HF).Methods HSC-T6 was divided into a blank group,astragaloside group,inhibitor group(using the Sirt1 inhibitor EX527),and astragaloside plus inhibitor group,Except for the blank group using 100 μmol·L-1 H2O2 to create a model of oxidative stress in HSC-T6,with 4 h of intervention in the modeling group,and 24 h of intervention in the modeling group,except for the modeling group.and Collagen 1 levels in cell supernatants;biochemical kit assay to determine oxidative stress-related indexes in cells;flow cytometry to detect the content of ROS in cells;immunofluorescence to detect the content ofα-SMA in cells;and real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR)and protein immunoblotting(Western blot)to detect SIRT1,NRF2,HO-1,α-SMA,Collagen1 mRNA and protein expression levels in each group of cells.Results Compared with the blank control group,the contents of α-SMA,Collagen1 and cellular MDA and ROS in the supernatants of HSC-T6 treated with H2O2 were significantly increased,whereas the contents of CAT and the activity of SOD in the cells were significantly decreased,the expression levels of mRNA and protein of Sirt1,Nrf2 and HO-1 in the cells were decreased,and the α-SMA,Collagen1 mRNA expression levels increased(P＜0.05);Compared with the model group,the contents of MDA and ROS in cells were significantly decreased,the CAT content and SOD activity were significantly increased,the expression levels of α-SMA and Collagen1 in the supernatant were decreased in the astragaloside Ⅳ group and astragaloside Ⅳ plus inhibitor group,the mRNA and protein expression levels of Sirt1,Nrf2 and HO-1 were increased,and the mRNA expression levels of α-SMA and Collagen1 were decreased(P＜0.05).Conclusion Astragaloside can attenuate HSC-T6 oxidative stress caused by H2O2 stimulation,reduce oxidative stress product production and collagen fiber deposition,thus achieving anti-HF,and its mechanism of action may be related to the regulation of the Sirt1/Nrf2/HO-1 signaling pathway.

Hepatic fibrosis （HF） is a widespread disease caused by various forms of chronic liver injury， significantly impacting human health. HF often has an insidious onset with inconspicuous symptoms， but in its advanced stages， it can progress to cirrhosis or even hepatocellular carcinoma. The pathogenic mechanisms of HF are highly complex， primarily characterized by excessive extracellular matrix （ECM） deposition. Autophagy is a lysosome-mediated degradation system employed by cells to recycle cellular contents， eliminate aggregated proteins， damaged organelles， and invading pathogens （such as viruses and bacteria） to maintain normal cellular function and dynamic balance. Autophagy can regulate various signaling pathways and factors， including mammalian target of rapamycin （mTOR）， adenosine monophosphate-activated protein kinase （AMPK）， and transforming growth factor-β （TGF-β）， to reduce the activation of hepatic stellate cells （HSCs） and hepatocyte necrosis and apoptosis， thereby mitigating ECM deposition and slowing the progression of HF. Numerous studies also suggest that traditional Chinese medicine （TCM） can effectively treat HF， and its mechanism of action may be related to autophagy. This article provides a review by summarizing recent literature in China and abroad on the mechanisms of autophagy， related signaling factors and pathways， as well as the role of TCM in regulating autophagy for the prevention and treatment of HF， aiming to offer insights and references for the development of TCM in the prevention and clinical rational medication in the treatment of HF.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Objective To study the mechanism of ferulic acid(FA)on hepatic fibrosis(HF)based on network pharmacology,and establish an in vitro model of rat hepatic stellate Cell-T6(HSC-T6)according to the results.Methods The potential targets of FA were screened through PubChem,swisstargetprediction and pharmmapper,and overlapped with the FA targets screened in disgenet,genecards and OMIM.Then,protein protein interaction(PPI)was analyzed by using string platform.Gene ontology(go)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for key targets by using R64 4.0.3,and the"component target disease"network diagram was constructed by Cytoscape 3.7.2 software.Based on this,the proliferation of HSC-T6 was detected by cell counting kit-8(CCK-8)method,and the grouping was determined:blank group and low-dose group(100 μg·mL-1 FA),medium dose group(200 μg·mL-1 FA),high dose group(400 μg·mL-1 FA)and positive control group(200 μg·mL-1 colchicine),the migration ability of HSC-T6 was detected by scratch test,and the content of HSC-T6 was detected by enzyme linked immunosorbent assay(ELISA)α-Alpha smooth muscle actin,α-Flow cytometry was used to detect the changes of HSC-T6 cycle,quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of JAK2 and STAT3 mRNA,and Western Blot was used to detect the molecular expression of JAK2 and STAT3 protein.Results 254 intersection targets of FA and HF were obtained.The core targets were signal transducer and activvator of Transcription(STAT3),albumin(ALB),protein kinase B(AKT1),tumor suppressor protein p53(TP53),epidermal growth factor receptor(EGFR)and caspase-3(CASP3).KEGG analysis showed that the action pathway of FA on HF mainly involved phosphatidylinositol 3 kinase protein kinase B(PI3K-Akt),vascular endothelial growth factor(VEGF),Janus kinase/signal transducer and activator of transcription(JAK/STAT)Tumor necrosis factor(TNF)and other pathways.The experimental results showed that in CCK-8 experiment,scratch experiment and ELISA experiment,compared with the blank group,the cell proliferation rate,migration ability and the expression of α-SMA protein decreased significantly(P<0.05).Compared with the blank group,the cycle arrest rate of low,medium and high dose groups and positive control group increased significantly(P<0.05).Compared with the blank group,the molecular weight and mRNA expression of JAK2 and STAT3 protein in low,medium and high dose groups and positive control group decreased gradually(P<0.05).Conclusion FA has the characteristics of multi-channel and multi-target.FA may inhibit the apoptosis of hepatic stellate cell(HSC)by down regulating JAK2 and STAT3 targets.