1.Clinical study on noninfectious fever of endovascular aortic repair
Zhengyue QIAN ; Yao FU ; Wenbo ZHOU ; Bingbing MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):275-280
Objective To analyze the clinical characteristics and risk factors of noninfectious fever after endovascular repair of aortic dilatation diseases, and to explore management strategies. Methods A retrospective analysis was conducted on the clinical data of patients who underwent endovascular aortic repair for aortic dilatation diseases from January 2021 to October 2023. Based on inclusion and exclusion criteria, the enrolled patients were divided into a febrile group and an afebrile group according to the presence of postoperative fever. Clinical data, including demographics and surgical details, were compared between the two groups. Multivariate logistic regression analysis was performed on indicators with P≤0.05 in the univariate analysis, and receiver operating characteristic (ROC) curves were generated to analyze the predictive value of risk factors for postoperative noninfectious fever. Results A total of 305 patients were included in the final analysis. Postoperative noninfectious fever occurred in 75.08% (229/305) of the patients, with 98.25% of cases occurring within the first two postoperative days. The febrile group (n=229) had a median age of 65.0 (IQR: 53.0, 73.0) years with 83.4% males, while the afebrile group (n=76) had a median age of 71.0 (IQR: 65.0, 76.7) years with 84.2% males. Univariate analysis showed that the age, prevalence of coronary heart disease, preoperative statin use, and prevalence of aortic aneurysm were significantly lower in the febrile group compared to the afebrile group. Logistic regression analysis indicated that age, surgical site, disease type, preoperative elevated body temperature, and stent type were significantly associated with noninfectious fever, while preoperative statin use was negatively correlated. ROC curve analysis demonstrated that age, surgical site, preoperative elevated body temperature, and stent type had significant predictive value for postoperative noninfectious fever (P<0.01). Conclusion Noninfectious fever is highly prevalent following aortic repair. The relationship between fever and infection should be comprehensively evaluated based on risk factors and changes in the patient's condition to promote the rational use of antibiotics.
2.Research advances of immune checkpoint inhibitors for neoadjuvant therapy in locally advanced gastric cancer
Ying SHA ; Ke YU ; Jiajia JIA ; Yufan TANG ; Bingbing WEN ; Baiquan ZHOU ; Shumei XU ; Ruifang FAN
Chinese Journal of Digestive Surgery 2025;24(9):1214-1220
Gastric cancer is one of the most common malignant tumors in the digestive system, characterized by high incidence and mortality rates. In recent years, with the rapid develop-ment of molecular immunology, the application of immune checkpoint inhibitors (ICIs) in neoadju-vant therapy has significantly improved pathological response rates and survival outcomes for patients with resectable locally advanced gastric cancer. The authors systematically review current research progress on combination strategies involving immune checkpoint inhibitors in neoadjuvant therapy for locally advanced gastric cancer, aiming to provide an evidence for optimizing individua-lized therapeutic regimens.
3.First Stage Ultrasonic Indicator-Based Nomogram Model for Predicting Vaginal Delivery in Nulliparous Women
Sen LIU ; Zhenyu CHEN ; Wan ZHONG ; Xiaoming CHEN ; Bingbing WANG ; Ting ZHANG
Chinese Journal of Medical Imaging 2025;33(8):872-879
Purpose To explore factors influencing vaginal delivery during the first stage of labor using intrapartum ultrasound and to construct predictive models for delivery decision-making.Materials and Methods A total of 473 nulliparous women admitted to Heping Hospital,Northern Theater General Hospital from July to December 2021 were prospectively enrolled as the training set.Clinical data on admission and fetal biometric parameters(biparietal diameter,femur length,head circumference and abdominal circumference)measured within one week before delivery were collected.Ultrasound assessments of fetal position,angle of progression(AOP)and head-perineum distance(HPD)were performed during the first stage of labor.The latent phase group(n=255)was subdivided into vaginal delivery group(n=186)and cesarean section group(n=69);the active phase group(n=218)was divided into vaginal delivery group(n=168)and cesarean section group(n=50).The associations between fetal position,AOP,HPD and vaginal delivery were analyzed,and predictive models were constructed for the latent phase(model 1)and active phase(model 2).A validation set of 547 women from January to September 2022 was used to evaluate model performance via area under the curve(AUC),calibration curves and decision curve analysis.Results In the latent phase,multivariate regression identified maternal height(OR=3.970,P=0.002),pre-pregnancy body mass index(OR=0.893,P=0.036),labor onset type(OR=2.415,P=0.045),neonatal birth weight(OR=3.728,P=0.002),AOP(OR=11.649,P<0.001)and HPD(OR=4.240,P=0.004)as significant predictors.The training and validation sets showed AUCs of 0.917 and 0.869,respectively.Goodness-of-fit tests indicated excellent model calibration(χ2=3.437,P=0.904;χ2=10.877,P=0.209).Decision curve analysis demonstrated strong clinical utility.For the active phase,significant predictors included maternal height(OR=6.532,P<0.001),neonatal birth weight(OR=11.890,P<0.001),fetal position(OR=4.600,P=0.003),AOP(OR=7.229,P<0.001)and HPD(OR=4.722,P=0.005).AUCs were 0.943(training)and 0.906(validation),with good calibration(χ2=4.340,P=0.740;χ2=9.836,P=0.277)and clinical applicability.Conclusion First stage ultrasound assessment of fetal position,AOP and HPD correlates with delivery outcomes.The developed nomogram models combining these parameters with clinical factors provide valuable guidance for delivery decision-making.
4.Effect of caprylic acid on lipid accumulation in primary hepatocytes of calves
Tianjiao YANG ; Yaqi CHANG ; Yunfei LUAN ; Jihang LI ; Zexin ZHANG ; Chuang XU ; Bingbing ZHANG ; Wei YANG
Chinese Journal of Veterinary Science 2025;45(7):1485-1492
The purpose of this study was to investigate the effect of medium-chain fatty acids(MC-FAs)caprylic acid(C8∶0)on lipid metabolism of calf hepatocytes.Primary calf hepatocytes were extracted and cultured,and 1.2 mmol/L nonesterified fatty acids(NEFAs)were added to the hep-atocytes to construct a model of hepatic lipid deposition in primary calf hepatocytes,Five process-ing groups have been set up:Control group(Ctrl),NEFA added group(NEFA),C8∶0 1.2 mmol/L treatment group(C8∶0 1.2),NEFA+C8∶0 0.2 mmol/L treatment group(NEFA+C8∶00.2),C8∶0 0.2 mmol/L treatment group(C8∶0 0.2).Stimulate calf liver cells for 12 hours,and the levels of triglyceride(TG),lipid oxidation(MDA),hydrogen peroxide(H2O2)and total SOD activity were detected by biochemical kit,and FAS,a protein related to lipid synthesis,was detec-ted by Western blot.The results showed that compared with the control group,the concentrations of TG,MDA and H2O2 in NEFA group increased significantly(P<0.01),and the activity of SOD decreased significantly(P<0.05).The protein expression levels of FAS,ACC1,DGAT2 and SREBP-1C were significantly up-regulated(P<0.01),while the expression level of CPT1A was significantly down-regulated(P<0.01).Compared with the NEFA group,the protein expression levels of SREBP-1C and DGAT2 in the NEFA+C8∶0(concentration 0.2 mmol/L)group de-creased significantly(P<0.05),and the protein expression level of fatty acid β-oxidation related molecule CPT1A was slightly higher than that in the NEFA group,but there was no statistical sig-nificance(P>0.05),and the MDA level in hepatocytes decreased significantly(P<0.05).In a word,the results of this study show that C8∶0 has antioxidant effect,which can effectively reduce the liver injury caused by oxidative stress,regulate the expression of liver fat gene,and then pro-tect liver injury.
5.Clinical characteristics and influencing factors for noninfectious fever in elderly patients after aortic repair surgery
Zhengyue QIAN ; Yao FU ; Ying GONG ; Bingbing MA
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1036-1041
Objective To explore the clinical characteristics and features of noninfectious fever in elderly patients with aortic dilation disease.Methods A total of 599 elderly patients diagnosed with aortic dilation disease(including 274 cases of acute disease and 325 cases of chronic disease)in the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2021 to June 2024 were recruited.According to their age,the patients with acute disease were divided into aged group 1(105 cases)and non-age group 1(169 cases),and those with chronic disease were into aged group 2(231 cases)and non-age group 2(94 cases).For the 520 patients(246 cases of acute disease and 274 cases of chronic disease)subjected for endovascular repair surgery,they were assigned into aged group 3(90 cases)and non-aged group 3(156 cases)for those with acute dis-ease,and aged group 4(206 cases)and non-aged group 4(68 cases)for those with chronic disease.For the 230 patients experiencing postoperative non-infectious fever,they were divided into acute-febrile(50 cases),acute-afebrile(20 cases),chronic-febrile(106 cases)and chronic-afebrile(54 cases)groups.Their general data was compared among the groups.Multivariate logistic regression analysis was conducted to identify the risk factors for postoperative noninfectious fever.ROC curve was plotted to analyze the predictive performance of our model for postoperative noninfec-tious fever.Results The surgical rate of endovascular repair surgery was 86.81%(520/599).The aged patients had significantly lower incidences of postoperative fever and non-infectious fever than the non-aged patients(P<0.05,P<0.01).There were no statistical differences in the ratio of using first and second generation cephalosporins or clindamycin and the duration of postopera-tive medication between the febrile group and afebrile group(P>0.05).Multivariate logistic re-gression analysis showed that for acute disease,implantation of polytetrafluoroethylene stents(OR=7.931,95%CI:1.945-32.337,P=0.004)was a risk factor,while administration of statins(OR=0.160,95%CI:0.032-0.807,P=0.026)was a protective factor for non-infectious fever.ROC curve analysis indicated that showed our model based on above results of multivariate logis-tic regression analysis had an AUC value of 0.836,a sensitivity of 60.0%and a specificity of 95.0%.For chronic disease,implantation of polytetrafluoroethylene stents(OR=2.558,95%CI:1.250-5.235,P=0.010)and preoperative increased temperature(OR=4.615,95%CI:1.502-14.181,P=0.008)were risk factors for non-infectious fever.Based on these results,the construc-ted model obtained an AUC value of 0.714 in ROC curve analysis.Conclusion For elderly patients undergoing aortic repair surgery,it is unnecessary to upgrade the variety of antibiotics or extend the course of treatment due to advanced age.Individualized analysis of possible infections should be conducted to promote the rational use of antibiotics.
6.Drug resistance and genomic characteristics of clinically isolated hypermu-coviscous Klebsiella pneumoniae
Bingbing LI ; Dawei CHEN ; Liang LIU ; Min SUN ; Shuangshu LI ; Jie LI ; Pengfei YANG ; Yadong XING
Chinese Journal of Infection Control 2025;24(1):113-120
Objective To analyze the drug resistance and genomic characteristics of clinically isolated hypermuco-viscous Klebsiella pneumoniae(hmKp).Methods Klebsiella pneumoniae isolated from clinical specimens from the sentinel hospitals of National Pathogen Identification Network in Huai'an City from 2019 to 2023 were collected,strains were identified by VITEK 2 Compact,mucus phenotype was determined by string test,resistance of hmKp was determined by microbroth dilution method.Molecular typing was conducted by whole-genome sequencing tech-nology,annotation of virulence and resistance genes carried by strains was performed.Results A total of 60 strains of hmKp were collected,mainly isolated from sputum specimens(33.33%)and blood specimens(28.33%).The average genome size of 60 strains was 5.6 Mb,with an average GC content of 57.09%.Multilocus sequence typing(MLST)showed that there were 28 ST types,with the dominant ST types being ST1 1(11.67%),ST15(11.67%),and ST412(10.00%).Core genome MLST(cgMLST)analysis revealed that some strains were highly homologous,and no outbreak strains were found.Multidrug-resistant strains accounted for 60.00%,while imipe-nem-resistant strains accounted for 28.33%.64 types of resistance genes were carried,84.38%of which were loca-ted on mobile element.The carriage rates of fosfomycin-related resistance genes and extended-spectrum β-lactam an-tibiotic-related resistance genes were relatively high in the strains,at 100%and 98.33%,respectively.Among car-bapenem-resistance gene blaKPC-2,21.67%was carried by ST11,ST1,and ST15 strains,among bla NDM-5 gene,3.33%was carried by ST76 strain.A total of 101 virulence genes were carried,most were Colibactin and type Ⅵsecretion system-related virulence genes.All strains carried capsule synthesis regulation-related genes(rcsA,rcsB),efflux pump-related genes(acrA,acrB),and enterobacterin-related genes(entABCEF,fepABCDFG,fes).Conclusion Clinically isolated hmKp in Huai'an exhibits multidrug resistance,with dominant ST types ST11,ST15,and ST412,carrying multiple horizontally transferable resistance and virulence genes,prevention and control measures should be strengthened.
7.Protective effect of polydatin and its mechanism on liver injury in silicosis rat model
Shuaihui ZHANG ; Dongmin ZHOU ; Bingbing WU ; Jinchao LIU ; Yan YU ; Fuhai SHEN
China Occupational Medicine 2025;52(6):601-611
Objective To explore the protective effect of polydatin and its mechanism on secondary liver injury in silicosis rats based on network pharmacology and animal experiments. Methods i) Network pharmacology study. Based on multiple databases, the targets of polydatin effect related to silicosis and liver injury were collected, and the common targets of polydatin-silicosis-liver injury were screened to construct a protein-protein interaction network. Enrichment analyses were performed to identify core targets involved in the effects of polydatin on silicosis-associated secondary liver injury. The mechanism of action of polydatin in relieving silicosis and silicosis-associated secondary liver injury was investigated, in which polydatin served as molecular docking ligand. ii) Animal experimental validation. Specific pathogen free male SD rats were randomly divided into three groups, with 10 rats per group. Rats in the model and intervention groups received 1 mL of a silica suspension at a mass concentration of 50 g/L for modeling using a one-time non-tracheal exposure method. Then rats in the intervention group were injected intraperitoneally with polydatin solution at 30 mg/kg body weight, once daily starting from the first day after silica exposure, whereas rats in the control group received no treatment. Lung and liver histopathology of rats, which were randomly sacrificed on days 28 and 56 post-exposure in both groups, were examined. Biomarkers of liver injury and hepatic oxidative stress were measured, and hepatic expression of nuclear factor erythroid 2-related factor 2 (NRF2) related proteins was detected by Western blotting. Results i) Network pharmacology study results. A total of 137 polydatin-related targets, 14 812 silicosis-related targets, and 3 038 liver injury-related targets were identified, among which 69 were common targets and 28 were key targets. Gene Ontology analysis indicated that the key targets were involved in 1 883 pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified 137 pathways related to the targets. Molecular docking showed good binding affinities between polydatin and B-cell lymphoma 2 (BCL2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and NRF2. ii) Animal experimental validation results. Compared with the control group, rats in the model group showed increased collagen deposition in both lung and liver tissues, with hepatic degeneration, necrosis, and inflammatory cell infiltration on days 28 and 56 after silica exposure. The collagen in lung and liver tissues of rats on days 28 and 56 after silica exposure increased in the model group compared with the control group (all P<0.05). Meanwhile, serum alanine aminotransferase and aspartate aminotransferase activities, hepatic lactate dehydrogenase 5 activities and NADPH: quinone oxidoreductase 1 (NQO1) expression in liver tissue increased (all P<0.05), whereas hepatic superoxide dismutase activity and NRF2 expression were decreased (all P<0.05). The level of malondialdehyde and the relative expression of heme oxygenase-1 (HO-1) protein in liver tissue in rat of model group were higher than those in the control group (all P<0.05). These alterations were ameliorated in rats of the intervention group compared with the model group (all P<0.05). Conclusion Polydatin exerts protective effects against secondary liver injury in rats with silicosis. These effects may be mediated by regulation of core targets such as BCL2, IL6, TNF, and NRF2, modulation of inflammatory pathways including TNF and IL17 signaling, and activation of the NRF2/HO-1 pathway, thereby exerting synergistic anti-inflammatory, antioxidant, and antifibrotic effects via the "lung-liver axis".
8.Clinical characteristics and influencing factors for noninfectious fever in elderly patients after aortic repair surgery
Zhengyue QIAN ; Yao FU ; Ying GONG ; Bingbing MA
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1036-1041
Objective To explore the clinical characteristics and features of noninfectious fever in elderly patients with aortic dilation disease.Methods A total of 599 elderly patients diagnosed with aortic dilation disease(including 274 cases of acute disease and 325 cases of chronic disease)in the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2021 to June 2024 were recruited.According to their age,the patients with acute disease were divided into aged group 1(105 cases)and non-age group 1(169 cases),and those with chronic disease were into aged group 2(231 cases)and non-age group 2(94 cases).For the 520 patients(246 cases of acute disease and 274 cases of chronic disease)subjected for endovascular repair surgery,they were assigned into aged group 3(90 cases)and non-aged group 3(156 cases)for those with acute dis-ease,and aged group 4(206 cases)and non-aged group 4(68 cases)for those with chronic disease.For the 230 patients experiencing postoperative non-infectious fever,they were divided into acute-febrile(50 cases),acute-afebrile(20 cases),chronic-febrile(106 cases)and chronic-afebrile(54 cases)groups.Their general data was compared among the groups.Multivariate logistic regression analysis was conducted to identify the risk factors for postoperative noninfectious fever.ROC curve was plotted to analyze the predictive performance of our model for postoperative noninfec-tious fever.Results The surgical rate of endovascular repair surgery was 86.81%(520/599).The aged patients had significantly lower incidences of postoperative fever and non-infectious fever than the non-aged patients(P<0.05,P<0.01).There were no statistical differences in the ratio of using first and second generation cephalosporins or clindamycin and the duration of postopera-tive medication between the febrile group and afebrile group(P>0.05).Multivariate logistic re-gression analysis showed that for acute disease,implantation of polytetrafluoroethylene stents(OR=7.931,95%CI:1.945-32.337,P=0.004)was a risk factor,while administration of statins(OR=0.160,95%CI:0.032-0.807,P=0.026)was a protective factor for non-infectious fever.ROC curve analysis indicated that showed our model based on above results of multivariate logis-tic regression analysis had an AUC value of 0.836,a sensitivity of 60.0%and a specificity of 95.0%.For chronic disease,implantation of polytetrafluoroethylene stents(OR=2.558,95%CI:1.250-5.235,P=0.010)and preoperative increased temperature(OR=4.615,95%CI:1.502-14.181,P=0.008)were risk factors for non-infectious fever.Based on these results,the construc-ted model obtained an AUC value of 0.714 in ROC curve analysis.Conclusion For elderly patients undergoing aortic repair surgery,it is unnecessary to upgrade the variety of antibiotics or extend the course of treatment due to advanced age.Individualized analysis of possible infections should be conducted to promote the rational use of antibiotics.
9.Analysis of the Construction and Path of China's Hospital Digital Transformation Model Based on the Multiple Case Study
Mengke YANG ; Sisi CHEN ; Jie XIN ; Yong GAO ; Hui XIAO ; Bingbing TUO ; Zhuxin YAO ; Zhiguo ZHANG ; Lining SHEN
Chinese Hospital Management 2025;45(5):39-44,53
Objective To investigate the drivers,stakeholders,core tasks,and differentiated development models of digital transformation in Chinese hospitals,develop a hospital digital transformation model,and propose advancement pathways.Methods Leveraging ROCCIPI theory,socio-technical systems theory,and social network theory,a multiple case study approach was employed to analyze four representative Chinese hospitals,examining the driving factors,social network relationship,and core tasks of digital transformation.Results Hospital digital transformation is a complex process driven by regulations,opportunities,and capabilities,requiring efficient collaboration among stakeholders focused on patient services,clinical operations,hospital management,and security.It identified three development models-ecology-oriented,regional integration,and grassroots enhancement—based on the distinct characteristics of the hospitals.A theoretical model for digital transformation in four Chinese hospitals was developed,along with proposed pathways and strategies.Conclusion It presents a digital transformation model and advancement pathways for hospitals through multiple case analyses,addressing the limited perspectives of existing research and providing a reference for practice.
10.Exploring the mechanism of Xiaoqinglong decoction on endothelial-mesenchymal transition in pulmonary arterial hypertension based on the principle of resolving the exterior and expanding the collaterals'principle
Jinbo ZHANG ; Wenxin ZHANG ; Bingbing FAN ; Zhiyong YANG ; Zhengkun TIAN ; Chunhe WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(4):433-443
Objective To analyze the role and mechanism of Xiaoqinglong decoction in alleviating the pathological process of pulmonary arterial hypertension(PAH),and to observe the effect of Xiaoqinglong decoction on endothelial-mesenchymal transition(EMT)in human pulmonary arterial endothelial cell(HPAEC)and the involvement of the Toll-like receptor/nuclear factor-κB/hypoxia-inducible factor-1α(TLR/NF-κB/HIF-1α)pathway in this mechanism.Methods Thirty-six male Sprague Dawley(SD)rats and HPAEC were randomly divided into control group,model group,Xiaoqinglong decoction plus Earthworm group,Bosentan tablet group,dimethyl sulfoxide(DMSO)group,and monophosphoryl lipid A(MPL)group.PAH rat models and HPAEC models were established by hypoxic exposure.The Xiaoqinglong decoction plus Earthworm group received intragastric administration Xiaoqinglong decoction plus Earthworm(5 g·kg-1·d-1)or cultured with 10%corresponding drug serum,the Bosentan group received Bosentan(100 mg·kg-1·d-1)by gavage or cultured with 10%corresponding drug serum,the MPL group received 1 μg MPL,and the DMSO group received an equivalent volume of the DMSO and corn oil mixed solvent as a negative control for the MPL group.The hemodynamic parameters,including mean pulmonary arterial pressure(mPAP),right ventricular systolic pressure(RVSP),and the maximum rate of right ventricular pressure(+dp/dt max),were measured via right heart catheterization.After euthanasia,lung and heart tissues were collected to assess the right ventricular hypertrophy index(RVHI);hematoxylin-eosin(HE)staining was used to observe the degree of right ventricular cardiomyocyte hypertrophy and to calculate the average intima-media thickness(IMT)in small pulmonary arteries;Western blotting was used to detect the protein expression levels of proliferating cell nuclear antigen(PCNA),CD68,TLR4,NF-κB,HIF-1α,vascular endothelial cadherin,and vimentin;cell counting kit-8(CCK-8),Transwell,and scratch assays were used to observe cell proliferation and migration;Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of interleukins(IL-8,IL-6),tumor necrosis factor-α(TNF-α),endothelin-1(ET-1),and nitric oxide(NO).Results Compared with the model group,the Xiaoqinglong decoction plus Earthworm group showed significant reductions in mPAP,RVSP,RVHI,and IMT in PAH rats[mPAP(mmHg,1 mmHg≈0.133 kPa):22.17±1.94 vs.42.00±4.90,RVSP(mmHg):34.67±3.20 vs.52.83±3.76,RVHI:0.402±0.057 vs.0.822±0.101,IMT:(37.85±2.49)%vs.(62.06±4.52)%,all P<0.05],and a significant increase in+dP/dT max(mmHg/s:2 730.83±137.89 vs.1 718.33±148.36,P<0.05).Western blotting and ELISA results showed that compared with the model group,the Xiaoqinglong decoction plus Earthworm group had significantly lower protein expression of PCNA and CD68 in lung tissue,and levels of inflammatory factors(IL-6,IL-8,TNF-α)in rat serum[lung tissue:PCNA protein expression(PCNA/GAPDH)was 1.56±0.08 vs.2.20±0.26,CD68 protein expression(CD68/GAPDH):1.46±0.09 vs.2.60±0.23;serum:IL-8(ng/L)was 39.67±6.28 vs.149.17±7.49,IL-6(ng/L):81.00±6.63 vs.211.00±25.31,TNF-α(ng/L):213.17±24.86 vs.799.50±43.51,all P<0.05].In vitro experiments,compared with the model group,Xiaoqinglong decoction plus Earthworm inhibited abnormal proliferation(A value:2.052±0.087 vs.2.242±0.057,P<0.05)and migration[number of migrating cells(per field):101.33±12.01 vs.226.67±17.56,P<0.05]of HPAEC,and reversed the EMT process,manifested as upregulation of vascular endothelial cadherin protein expression levels(vascular endothelial cadherin/GAPDH:0.39±0.06 vs.0.12±0.03,P<0.05)and downregulation of vimentin protein expression(vimentin/GAPDH:4.96±0.33 vs.7.89±0.44,P<0.05).Western blotting results indicated that compared with the model group,the protein expression levels of TLR4,the ratio of phosphorylated p65 to total p65,and HIF-1α in both lung tissue and HPAEC were significantly reduced in the Xiaoqinglong decoction plus Earthworm group[lung tissue:TLR4 protein expression(TLR4/GAPDH)was 3.13±0.20 vs.4.38±0.30,p-p65/p65 ratio:7.11±0.81 vs.12.73±1.80,HIF-1α protein expression(HIF-1α/GAPDH):2.37±0.32 vs.4.45±0.34;HPAEC:TLR4 protein expression(TLR4/GAPDH)was 1.42±0.03 vs.2.43±0.05,p-p65/p65 ratio:6.01±1.84 vs.11.28±1.06,HIF-1α protein expression(HIF-1α/GAPDH)was 3.24±0.17 vs.5.50±0.44,all P<0.05],accompanied by upregulated vascular endothelial cadherin protein expression(vascular endothelial cadherin/GAPDH:0.66±0.03 vs.0.49±0.03,P<0.05)and downregulated vimentin protein expression(vimentin/GAPDH:1.81±0.12 vs.2.47±0.10,P<0.05),indicating that Xiaoqinglong decoction plus Earthworm inhibits the EMT process in endothelial cells by suppressing the activation of the TLR/NF-κB/HIF-1α pathway.Experiments with a TLR agonist further confirmed that activation of the TLR pathway reverses the protective effects of Xiaoqinglong decoction plus Earthworm,as shown by the MPL group compared to the DMSO group having significantly increased protein expression of the p-p65/p65 ratio and HIF-1α[p-p65/p65 ratio:2.17±0.35 vs.1.08±0.14,HIF-1α/GAPDH:3.96±0.25 vs.1.03±0.10,both P<0.05],further decreased vascular endothelial cadherin protein expression(vascular endothelial cadherin/GAPDH:0.66±0.04 vs.0.99±0.02,P<0.05),further increased vimentin protein expression(vimentin/GAPDH:1.53±0.12 vs.0.93±0.07,P<0.05),along with enhanced cell migration capacity[number of migrating cells(per field):176.67±17.50 vs.107.00±11.14;cell migration rate in scratch assay:(34.32±2.82)%vs.(22.71±2.49)%,both P<0.05]and increased proliferation activity(48 hours A value:2.156±0.044 vs.1.810±0.088,P<0.05).Conclusions Xiaoqinglong decoction combined with Pheretima not only significantly reduces pulmonary artery pressure,improves cardiac function and mitigates pulmonary vascular fibrosis in PAH rats,but also alleviates pulmonary vascular remodeling by inhibiting inflammatory responses and EMT.It can further decrease the content of ET-1,increase the level of NO,and ameliorate vascular stenosis.This result further indicates that exterior-relieving medicines exert a significant dilating and supporting effect on the narrowed meridians and collaterals.

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