Coronary chronic total occlusion(CTO)remains a significant challenge in the field of interventional therapy for coronary artery disease.With advancements in interventional techniques,particularly retrograde approaches,the success rate of CTO interventions has improved.The key steps of retrograde intervention include traversing collateral channels with the retrograde guidewire,wiring the occlusion segment,and establishing antegrade access.In this case,the patient had a heavily calcified occlusion at the left circumflex artery(LCX)ostium jailed by the prior stent implanted in the left main and anterior descending arteries,making it difficult to establish antegrade access using conventional methods after retrograde guidewire crossing.The procedure was successfully completed by employing a domestically developed intravascular snare system combined with a pre-assembled extension catheter technique to capture the retrograde guidewire and establish antegrade access,followed by stent implantation at the LCX ostium.This innovative approach provides a new strategy for complex CTO retrograde interventions,particularly in cases where retrograde guidewire entry into the antegrade guiding catheter is challenging.

Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.

Background and purpose:Approximately 30%of patients with metastatic colorectal cancer(CRC)develops pulmonary metastasis,yet less than 10%are eligible for surgical resection.Radiofrequency ablation(RFA)serves as an alternative therapy for non-surgical candidates,but the relationship between its efficacy and tumor diameter remains controversial.This study aimed to investigate the impact of tumor size on survival outcomes and local progression risk in CRC patients with pulmonary metastasis after RFA,and to validate the clinical utility of a 3 cm threshold for prognosis.Methods:This retrospective study included CRC patients with pulmonary metastasis who underwent RFA at Fudan University Shanghai Cancer Center between January 2016 and December 2024.Patients were stratified into two groups based on maximum lesion diameter:≤3 cm(Small group)and 3-5 cm(Large group).Patient inclusion criteria:⑴ pathologically confirmed lung metastases originating from CRC,with metastases limited to the lungs or extra-pulmonary metastatic lesions having been radically treated;⑵ maximum lesion diameter<5 cm;⑶complete clinical data available;⑷ complete imaging data available,including computed tomography(CT)images during ablation and contrast-enhanced CT images during postoperative follow-up;⑸ follow-up time of at least＞6 months after RFA;⑹ technical complete ablation;⑺ fewer than 3 pulmonary metastatic lesions.Exclusion criteria:⑴ target lesions previously treated with local therapies such as RFA or radiotherapy;⑵ patients unable to tolerate RFA;⑶ patients with follow-up time＜6 months after RFA.Three senior interventional physicians performed percutaneous RFA under guidance of a 64-slice spiral CT scanner.Chest contrast-enhanced CT scans obtained 1 month after RFA were used as the baseline,followed by contrast-enhanced CT scans every 3 months for 1 year,then every 6 months for subsequent follow-up.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical approval number:2108241-11).Primary endpoints included overall survival(OS),progression-free survival(PFS),and local tumor progression(LTP).Kaplan-Meier analysis and multivariate COX regression were employed to evaluate the independent prognostic value of tumor size.Results:A total of 134 patients who met the inclusion criteria were ultimately enrolled,including 77 in the Small group and 57 in the Large group.With a median follow-up of 35 months,the≤3 cm group demonstrated superior 1-,3-,and 5-year OS rates(100.0%,95.1%,74.2%)compared to the 3-5 cm group(94.7%,36.8%,27.0%,P＜0.0001),and the≤3 cm group demonstrated superior 1-,3-,and 5-year PFS rates(90.9%,34.4%,23.3%)compared to the 3-5 cm group(13.8%,0.0%,0.0%,P＜0.000 1).The≤3 cm group also exhibited significantly lower 1-,3-,and 5-year LTP rates(0.0%,19.7%,33.6%)compared to the 3-5 cm group(46.0%,75.5%,75.5%,P＜0.000 1).Multivariable analysis identified tumor diameter＞3 cm as an independent predictor of worse OS[hazard ratio(HR)=6.49,95%CI:3.18-13.24,P＜0.001],while elevated preoperative carcinoembryonic antigen(CEA)(≥5 ng/mL)correlated with shorter OS(HR=1.82,P=0.033).Conclusion:CRC patients with pulmonary metastasis and tumor diameters of 3-5 cm exhibited significantly inferior survival outcomes after RFA compared to the≤3 cm group.A tumor diameter of 3 cm can serve as a critical threshold for selecting RFA indications,and combining preoperative CEA levels can optimize patient stratification.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.

Background and purpose:Approximately 30%of patients with metastatic colorectal cancer(CRC)develops pulmonary metastasis,yet less than 10%are eligible for surgical resection.Radiofrequency ablation(RFA)serves as an alternative therapy for non-surgical candidates,but the relationship between its efficacy and tumor diameter remains controversial.This study aimed to investigate the impact of tumor size on survival outcomes and local progression risk in CRC patients with pulmonary metastasis after RFA,and to validate the clinical utility of a 3 cm threshold for prognosis.Methods:This retrospective study included CRC patients with pulmonary metastasis who underwent RFA at Fudan University Shanghai Cancer Center between January 2016 and December 2024.Patients were stratified into two groups based on maximum lesion diameter:≤3 cm(Small group)and 3-5 cm(Large group).Patient inclusion criteria:⑴ pathologically confirmed lung metastases originating from CRC,with metastases limited to the lungs or extra-pulmonary metastatic lesions having been radically treated;⑵ maximum lesion diameter<5 cm;⑶complete clinical data available;⑷ complete imaging data available,including computed tomography(CT)images during ablation and contrast-enhanced CT images during postoperative follow-up;⑸ follow-up time of at least＞6 months after RFA;⑹ technical complete ablation;⑺ fewer than 3 pulmonary metastatic lesions.Exclusion criteria:⑴ target lesions previously treated with local therapies such as RFA or radiotherapy;⑵ patients unable to tolerate RFA;⑶ patients with follow-up time＜6 months after RFA.Three senior interventional physicians performed percutaneous RFA under guidance of a 64-slice spiral CT scanner.Chest contrast-enhanced CT scans obtained 1 month after RFA were used as the baseline,followed by contrast-enhanced CT scans every 3 months for 1 year,then every 6 months for subsequent follow-up.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical approval number:2108241-11).Primary endpoints included overall survival(OS),progression-free survival(PFS),and local tumor progression(LTP).Kaplan-Meier analysis and multivariate COX regression were employed to evaluate the independent prognostic value of tumor size.Results:A total of 134 patients who met the inclusion criteria were ultimately enrolled,including 77 in the Small group and 57 in the Large group.With a median follow-up of 35 months,the≤3 cm group demonstrated superior 1-,3-,and 5-year OS rates(100.0%,95.1%,74.2%)compared to the 3-5 cm group(94.7%,36.8%,27.0%,P＜0.0001),and the≤3 cm group demonstrated superior 1-,3-,and 5-year PFS rates(90.9%,34.4%,23.3%)compared to the 3-5 cm group(13.8%,0.0%,0.0%,P＜0.000 1).The≤3 cm group also exhibited significantly lower 1-,3-,and 5-year LTP rates(0.0%,19.7%,33.6%)compared to the 3-5 cm group(46.0%,75.5%,75.5%,P＜0.000 1).Multivariable analysis identified tumor diameter＞3 cm as an independent predictor of worse OS[hazard ratio(HR)=6.49,95%CI:3.18-13.24,P＜0.001],while elevated preoperative carcinoembryonic antigen(CEA)(≥5 ng/mL)correlated with shorter OS(HR=1.82,P=0.033).Conclusion:CRC patients with pulmonary metastasis and tumor diameters of 3-5 cm exhibited significantly inferior survival outcomes after RFA compared to the≤3 cm group.A tumor diameter of 3 cm can serve as a critical threshold for selecting RFA indications,and combining preoperative CEA levels can optimize patient stratification.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.