ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan （XJW）-containing serum interfering with endothelial-mesenchymal transition （EMT） in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW （4 g·kg^-1） to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum （4 g·kg^-1） according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group， β-catenin intervention/overexpression group， intervention/overexpression blank + XJW group， and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and active-Caspase-3］ and EMT-related proteins （E-cadherin， N-cadherin， and vimentin）. Real-time polymerase chain reaction （Real-time PCR） was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group， the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates （P<0.05， P<0.01）， elevated protein levels of Bax， active Caspase-3， and E-cadherin （P<0.05， P<0.01）， and decreased protein levels of Bcl-2 and Vimentin （P<0.05， P<0.01）. β-catenin mRNA expression was reduced in the β-catenin intervention group （P<0.05， 0.63 ± 0.15） and the intervention blank + XJW group （P<0.05， 0.79 ± 0.33）. Compared with the β-catenin intervention group， the β-catenin intervention + XJW group exhibited an increased apoptosis rate （P<0.01）， elevated Bax and active Caspase-3 protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and Vimentin protein levels （P<0.05）. β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group （P<0.01， 0.22 ± 0.08）. Compared with the intervention blank + XJW group， the β-catenin intervention + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax， active Caspase-3， and E-cadherin protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and vimentin protein levels （P<0.05， P<0.01）. β-catenin mRNA expression was also reduced （P<0.05）. Overexpression experiment results showed that compared with the overexpression blank group， the β-catenin overexpression group exhibited a reduced apoptosis rate （P<0.01）， while the overexpression blank + XJW group showed an increased apoptosis rate （P<0.05）. In the β-catenin overexpression and β-catenin overexpression + XJW groups， Bax and E-cadherin protein levels decreased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels increased （P<0.05）. In the overexpression blank + XJW group， Bax and E-cadherin levels increased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels decreased （P<0.05， P<0.01）. β-catenin mRNA expression increased in the β-catenin overexpression group （P<0.01， 7.26 ± 1.03） but decreased in the overexpression blank + XJW group （P<0.05， 0.73 ± 0.14）. Compared with the β-catenin overexpression group， the β-catenin overexpression + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax and E-cadherin levels （P<0.05）， and decreased N-cadherin and vimentin levels （P<0.05）. β-catenin mRNA expression was reduced （P<0.05， 4.65 ± 1.02）. Compared with the overexpression blank + XJW group， the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate （P<0.01）， decreased Bax and E-cadherin levels （P<0.01）， and increased Bcl-2， N-cadherin， and Vimentin levels （P<0.05）. β-catenin mRNA expression increased （P<0.01）. ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT， which is associated with the regulation of the Wnt/β-catenin pathway.

In 2026， the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases jointly published a Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis. This consensus proposes 16 statements and 42 recommendations centering on the following three most critical issues in the development of new drugs for primary biliary cholangitis： whether liver biochemical parameters and noninvasive assessments of liver fibrosis can be used as surrogate endpoints for clinical outcomes； how real-world data and real-world evidence can complement or support confirmatory studies in a manner compliant with regulatory requirements； how patient-reported outcomes can be standardized for the assessment of quality of life， pruritus， and fatigue. This article provides an excerpt and expert interpretation of the background， methodological framework， core statements， recommendations， and key figures and tables of this consensus， in order to provide a reference for the diagnosis and treatment of primary biliary cholangitis， drug evaluation， real-world study design， and the development of patient-centered clinical endpoints in China.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Third-line treatment for metastatic colorectal cancer(mCRC)refers to subsequent therapeutic interventions following the failure or intolerance of first-and second-line treatments.This represents a critical challenge in clinical practice and a core focus of translational medicine research in recent years.With advancements in molecular typing technologies and the emergence of novel therapies,the third-line treatment strategy has evolved from traditional chemotherapy toward precision targeting and immunotherapy.A comprehensive literature search was conducted across PubMed,ClinicalTrials.gov database and American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO)conference abstracts.Phase Ⅲ randomized controlled trials,phase Ⅰ/Ⅱ frontier clinical studies,and authoritative reviews were included,with an emphasis on data related to survival benefits,drug resistance mechanisms,and biomarkers.This review provided an in-depth analysis of significant progress in third-line treatment strategies for mCRC,encompassing standard therapies[regorafenib,fruquintinib,trifluridine/tipiracil,anti-epidermal growth factor receptor(EGFR)rechallenge therapy],targeted therapies(e.g.,BRAF V600E inhibitors,ERBB2 amplification inhibitors,KRAS G12C inhibitors)and immunotherapies[microsatellite instability-high(MSI-H)/deficient mismatch repair(dMMR),microsatellite stable(MSS)/proficient mismatch repair(pMMR)and target-immune combination therapies].Notable breakthroughs have been achieved in targeted therapies.Anti-EGFR rechallenge therapy extended the median overall survival(OS)to 17.3 months in RAS/BRAF wild-type patients identified through dynamic circulating tumor DNA(ctDNA)monitoring.However,drug resistance remains complex,with high secondary mutation rates necessitating further optimization of dynamic monitoring systems.For BRAF V600E mutations,triple therapy(encorafenib+binimetinib+cetuximab)demonstrated a median OS of 9.3 months[hazard ratio(HR)=0.52],surpassing conventional treatments.The combination of KRAS G12C inhibitor adagrasib with cetuximab achieved an objective response rate(ORR)of 34%and a median OS of 15.9 months,though tumor resistance continued to pose challenges.In the realm of immunotherapy,dual immunotherapy(nivolumab+ipilimumab)yielded a 4-year OS rate of 71%in MSI-H/dMMR patients.For MSS patients,immune-targeted combination strategies(e.g.,cabozantinib+atezolizumab)increased the ORR to 27.6%.Emerging therapies include artificial intelligence platforms for precision medicine,gut microbiota-based biomarkers and fecal microbiota transplantation,as well as advancements in chimeric antigen receptor-T(CAR-T)cell therapy.By summarizing the current status and progress of third-line treatment for mCRC,this review aims to inform clinical decision-making and guide future research directions.

Objective To establish a method for 11 main components of Hibisci Mutabilis Folium;To evaluate the quality of Hibisci Mutabilis Folium using the chemical pattern recognition,weighted TOPSIS and grey correlation degree fusion model.Methods A total of 18 batches of Hibisci Mutabilis Folium from main producing areas were collected,and the contents of caffeic acid,ferulic acid,salicylic acid,fraxetin,hyperoside,rutoside,isoquercitrin,kaempferol-3-O-rutinoside,tiliroside,β-sitosterol and eleucheroside were detected by external standard method.The extract,total ash and acid-insoluble ash were detected.The quality was systematically evaluated using chemical pattern recognition,weighted TOPSIS and grey correlation degree fusion model.Results The methodological verification showed that the linear relationship of each component was good,the repeatability and accuracy of the established method were good,the instrument precision was high,and the stability of the test solution of Hibisci Mutabilis Folium ultrasonically extracted with 70%methanol was good within 24 h.The content determination results showed that the quality difference between batches was large.Chemical pattern recognition analysis showed that 18 batches of Hibisci Mutabilis Folium were clustered obviously,and the quality difference compounds were identified as rutoside,caffeic acid,kaempferol-3-O-rutinoside,fraxetin and hyperoside.The relative closeness of 18 batches of samples was between 0.253 8 and 0.694 3.Conclusion The established multi-index quantitative method can reflect the quality differences of Hibisci Mutabilis Folium from different habitats.Chemical pattern recognition combined with weighted TOPSIS and grey correlation degree fusion model can comprehensively analyze the quality conditions of different batches of Hibisci Mutabilis Folium,which can establish a foundation for the quality analysis and evaluation of Hibisci Mutabilis Folium.

In recent years, the incidence of multiple primary lung cancer (MPLC) has been increasing, and it cannot be ignored in clinical practice. The treatment of MPLC is still controversial, but surgical treatment is recognized as the most important treatment. However, current studies have shown that the treatment of MPLC needs to develop multimodal treatment according to different patients. This review summarizes multiple treatment method for MPLC, including surgery, ablation, chemotherapy, radiotherapy, targeted therapy, and immunotherapy in order to enhance understanding of MPLC treatment.
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Humans ; Lung Neoplasms/surgery* ; Immunotherapy ; Combined Modality Therapy

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Third-line treatment for metastatic colorectal cancer(mCRC)refers to subsequent therapeutic interventions following the failure or intolerance of first-and second-line treatments.This represents a critical challenge in clinical practice and a core focus of translational medicine research in recent years.With advancements in molecular typing technologies and the emergence of novel therapies,the third-line treatment strategy has evolved from traditional chemotherapy toward precision targeting and immunotherapy.A comprehensive literature search was conducted across PubMed,ClinicalTrials.gov database and American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO)conference abstracts.Phase Ⅲ randomized controlled trials,phase Ⅰ/Ⅱ frontier clinical studies,and authoritative reviews were included,with an emphasis on data related to survival benefits,drug resistance mechanisms,and biomarkers.This review provided an in-depth analysis of significant progress in third-line treatment strategies for mCRC,encompassing standard therapies[regorafenib,fruquintinib,trifluridine/tipiracil,anti-epidermal growth factor receptor(EGFR)rechallenge therapy],targeted therapies(e.g.,BRAF V600E inhibitors,ERBB2 amplification inhibitors,KRAS G12C inhibitors)and immunotherapies[microsatellite instability-high(MSI-H)/deficient mismatch repair(dMMR),microsatellite stable(MSS)/proficient mismatch repair(pMMR)and target-immune combination therapies].Notable breakthroughs have been achieved in targeted therapies.Anti-EGFR rechallenge therapy extended the median overall survival(OS)to 17.3 months in RAS/BRAF wild-type patients identified through dynamic circulating tumor DNA(ctDNA)monitoring.However,drug resistance remains complex,with high secondary mutation rates necessitating further optimization of dynamic monitoring systems.For BRAF V600E mutations,triple therapy(encorafenib+binimetinib+cetuximab)demonstrated a median OS of 9.3 months[hazard ratio(HR)=0.52],surpassing conventional treatments.The combination of KRAS G12C inhibitor adagrasib with cetuximab achieved an objective response rate(ORR)of 34%and a median OS of 15.9 months,though tumor resistance continued to pose challenges.In the realm of immunotherapy,dual immunotherapy(nivolumab+ipilimumab)yielded a 4-year OS rate of 71%in MSI-H/dMMR patients.For MSS patients,immune-targeted combination strategies(e.g.,cabozantinib+atezolizumab)increased the ORR to 27.6%.Emerging therapies include artificial intelligence platforms for precision medicine,gut microbiota-based biomarkers and fecal microbiota transplantation,as well as advancements in chimeric antigen receptor-T(CAR-T)cell therapy.By summarizing the current status and progress of third-line treatment for mCRC,this review aims to inform clinical decision-making and guide future research directions.

Objective To establish a method for 11 main components of Hibisci Mutabilis Folium;To evaluate the quality of Hibisci Mutabilis Folium using the chemical pattern recognition,weighted TOPSIS and grey correlation degree fusion model.Methods A total of 18 batches of Hibisci Mutabilis Folium from main producing areas were collected,and the contents of caffeic acid,ferulic acid,salicylic acid,fraxetin,hyperoside,rutoside,isoquercitrin,kaempferol-3-O-rutinoside,tiliroside,β-sitosterol and eleucheroside were detected by external standard method.The extract,total ash and acid-insoluble ash were detected.The quality was systematically evaluated using chemical pattern recognition,weighted TOPSIS and grey correlation degree fusion model.Results The methodological verification showed that the linear relationship of each component was good,the repeatability and accuracy of the established method were good,the instrument precision was high,and the stability of the test solution of Hibisci Mutabilis Folium ultrasonically extracted with 70%methanol was good within 24 h.The content determination results showed that the quality difference between batches was large.Chemical pattern recognition analysis showed that 18 batches of Hibisci Mutabilis Folium were clustered obviously,and the quality difference compounds were identified as rutoside,caffeic acid,kaempferol-3-O-rutinoside,fraxetin and hyperoside.The relative closeness of 18 batches of samples was between 0.253 8 and 0.694 3.Conclusion The established multi-index quantitative method can reflect the quality differences of Hibisci Mutabilis Folium from different habitats.Chemical pattern recognition combined with weighted TOPSIS and grey correlation degree fusion model can comprehensively analyze the quality conditions of different batches of Hibisci Mutabilis Folium,which can establish a foundation for the quality analysis and evaluation of Hibisci Mutabilis Folium.

To study the clinical correlation between fasting plasma glucose, lipid metabolism, prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia, and to explore the combined effect as diagnostic indicators. A total of 108 patients with benign prostatic hyperplasia treated in Beijing University of Chinese Medicine Third Affiliated Hospital from June 2021 to March 2023 were retrospectively analyzed as the hyperplasia group, and 98 healthy physical examination personnel were selected as the control group during the same period. Compare the differences in levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small and dense low-density lipoprotein cholesterol (sdLDL-C), homocysteine, lipoprotein a (LPa), prostate specific antigen (PSA), and free prostate specific antigen (fPSA) between two groups of patients. Using Pearson analysis method to analyze the correlation between the above indicators and the size of prostate volume in patients with benign prostatic hyperplasia; using multiple linear regression to analyze the influencing factors of prostate volume enlargement; draw receiver operating characteristic (ROC) curves and analyze the application value of individual and combined detection of HDL, FPG, PSA, and fPSA. The results showed that there were significant differences in HDL, FPG, PSA, and fPSA levels between the control group and the proliferative group( P<0.05). The size of prostate volume is negatively correlated with HDL( r=-0.183, P<0.05) and positively correlated with FPG ( r=0.202, P<0.05), PSA( r=0.412, P<0.05), and fPSA( r=0.425, P<0.05). The results of multiple linear regression analysis showed that HDL( P=0.000), FPG( P=0.048), PSA( P=0.044), and fPSA ( P=0.012) were risk factors for increased volume of benign prostatic hyperplasia; ROC curve analysis shows that the AUC of HDL, FPG, PSA, and fPSA combined detection is 0.823, which is better than individual detection. In conclusion,HDL, FPG, PSA, fPSA has close correlation with hyperplasia of prostate, the joint detection may has better prediction for benign prostatic hyperplasia.