Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To understand the economic losses due to healthcare-associated infection(HAI)in patients after Da Vinci robotic thoracic surgery,and provide basis for preventing and controlling HAI after robotic surgery.Methods Patients who underwent Da Vinci robotic surgery from April 2019 to April 2023 were retrospective stu-died.Patients were divided into HAI group and non-HAI group based on the occurrence of postoperative infection.Through 1∶1 propensity score matching(PSM),31 cases were included in each group,economic losses of two groups of patients were compared.Results A total of 921 patients who underwent Da Vinci robotic thoracic surgery were included in the study,51 cases with HAI(HAI group)and 870 without HAI(non-HAI group).After 1∶1 PSM,31 cases were included in each group.Four covariates were compared between two groups of patients before PSM,namely gender,age,comorbidities,and the American Society of Anesthesiologists(ASA)grading,all with statistically significant differences(all P＜0.05).After PSM,distribution of the above covariates reached equilib-rium between the two groups(both P＞0.05).The median total expense for HAI group before PSM during hospi-talization was 88 711.72 Yuan,while 78 509.46 Yuan for the non-HAI group.The direct economic losses caused by HAI after Da Vinci robot surgery was 10 202.26 Yuan,mainly increased by expense of medicine,nursing,laborato-ry diagnosis,etc.Difference in western medicine expense was the highest(8 839.12 Yuan),out of which expense of antimicrobial agents accounted for the highest proportion(73.55％).Difference in daily hospitalization expense between HAI-group and non-HAI group was 502.38 Yuan.Length of hospital stay of patients in HAI group and non-HAI group were(21.59±10.62)and(13.92±9.21)days,respectively,with statistical differences(all P＜0.05).Conclusion The occurrence of HAI in patients undergoing Da Vinci robotic thoracic surgery leads to direct economic losses,with obvious increases in expenses of nursing,laboratory diagnosis,western medicine(mainly an-timicrobial agents).Length of hospital stay of patients also prolongs.

OBJECTIVE To observe the isolation rates and drug resistance rates of Acinetobacter baumannii strains isolated from intensive care unit(ICU)patients in 8 consecutive years so as to provide bases for reasonable clinical application of antibiotics and control of infections.METHODS The isolation rates and specimens from which the A.baumannii and carbapenem-resistant A.baumannii(CRAB)strains were isolated from ICU patients of the First People's Hospital of Changzhou between 2017 and 2024 were retrospectively analyzed.The trends of the drug resistance rates were observed.RESULTS Totally 2078(18.03％)strains of A.baumannii were isolated from the ICU patients from 2017 to 2024,and there was no significant difference in the changing trend among the years(x2=-1.573,P=0.116).Among the A.baumannii strains that were isolated from 2017 to 2024,58.08％were isolated from sputum,and 24.25％from lavage fluid specimens;the percentage of sputum specimens showed a downward trend in the 8 years(x2=-8.257,P＜0.001),while the percentage of lavage fluid speci-mens showed an upward trend(x2=12.964,P＜0.001).The isolation rate of the CRAB strains was 91.48％in 2017,92.61％in 2018,92.56％in 2019,82.53％in 2020,52.44％in 2021,showing a down-ward trend,and it began to rise in 2022-2024,there was significant difference(x2=-2.277,P=0.012).The isolation rates of the CRAB strains from both sputum and lavage fluid specimens showed downward trends and then upward trends(all P＜0.05).The drug resistance rates of the A.baumannii strains to piperacillin and minocycline showed slow upward trends,while the drug resistance rates to gentamicin and tigecycline showed downward trends,and there were significant differences(P＜0.05).The drug resistance rates of the A.bau-mannii strains to imipenem and meropenem remained more than 90％.CONCLUSIONS Acinetobacter spp is the major pathogen causing the hospital-acquired infection.The isolation rate of CRAB strains shows a downward trend then a upward trend in recent two years.It is necessary for the hospital to standardize the submission of spu-tum specimens and increase the aseptic submission.The A.baumannii strains show high drug resistance rates to the commonly used antibiotics.Polymyxin B,tigecycline and minocycline are the major antibiotics for treatment of CRAB infection.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

OBJECTIVE To observe the isolation rates and drug resistance rates of Acinetobacter baumannii strains isolated from intensive care unit(ICU)patients in 8 consecutive years so as to provide bases for reasonable clinical application of antibiotics and control of infections.METHODS The isolation rates and specimens from which the A.baumannii and carbapenem-resistant A.baumannii(CRAB)strains were isolated from ICU patients of the First People's Hospital of Changzhou between 2017 and 2024 were retrospectively analyzed.The trends of the drug resistance rates were observed.RESULTS Totally 2078(18.03％)strains of A.baumannii were isolated from the ICU patients from 2017 to 2024,and there was no significant difference in the changing trend among the years(x2=-1.573,P=0.116).Among the A.baumannii strains that were isolated from 2017 to 2024,58.08％were isolated from sputum,and 24.25％from lavage fluid specimens;the percentage of sputum specimens showed a downward trend in the 8 years(x2=-8.257,P＜0.001),while the percentage of lavage fluid speci-mens showed an upward trend(x2=12.964,P＜0.001).The isolation rate of the CRAB strains was 91.48％in 2017,92.61％in 2018,92.56％in 2019,82.53％in 2020,52.44％in 2021,showing a down-ward trend,and it began to rise in 2022-2024,there was significant difference(x2=-2.277,P=0.012).The isolation rates of the CRAB strains from both sputum and lavage fluid specimens showed downward trends and then upward trends(all P＜0.05).The drug resistance rates of the A.baumannii strains to piperacillin and minocycline showed slow upward trends,while the drug resistance rates to gentamicin and tigecycline showed downward trends,and there were significant differences(P＜0.05).The drug resistance rates of the A.bau-mannii strains to imipenem and meropenem remained more than 90％.CONCLUSIONS Acinetobacter spp is the major pathogen causing the hospital-acquired infection.The isolation rate of CRAB strains shows a downward trend then a upward trend in recent two years.It is necessary for the hospital to standardize the submission of spu-tum specimens and increase the aseptic submission.The A.baumannii strains show high drug resistance rates to the commonly used antibiotics.Polymyxin B,tigecycline and minocycline are the major antibiotics for treatment of CRAB infection.

Objective To understand the economic losses due to healthcare-associated infection(HAI)in patients after Da Vinci robotic thoracic surgery,and provide basis for preventing and controlling HAI after robotic surgery.Methods Patients who underwent Da Vinci robotic surgery from April 2019 to April 2023 were retrospective stu-died.Patients were divided into HAI group and non-HAI group based on the occurrence of postoperative infection.Through 1∶1 propensity score matching(PSM),31 cases were included in each group,economic losses of two groups of patients were compared.Results A total of 921 patients who underwent Da Vinci robotic thoracic surgery were included in the study,51 cases with HAI(HAI group)and 870 without HAI(non-HAI group).After 1∶1 PSM,31 cases were included in each group.Four covariates were compared between two groups of patients before PSM,namely gender,age,comorbidities,and the American Society of Anesthesiologists(ASA)grading,all with statistically significant differences(all P＜0.05).After PSM,distribution of the above covariates reached equilib-rium between the two groups(both P＞0.05).The median total expense for HAI group before PSM during hospi-talization was 88 711.72 Yuan,while 78 509.46 Yuan for the non-HAI group.The direct economic losses caused by HAI after Da Vinci robot surgery was 10 202.26 Yuan,mainly increased by expense of medicine,nursing,laborato-ry diagnosis,etc.Difference in western medicine expense was the highest(8 839.12 Yuan),out of which expense of antimicrobial agents accounted for the highest proportion(73.55％).Difference in daily hospitalization expense between HAI-group and non-HAI group was 502.38 Yuan.Length of hospital stay of patients in HAI group and non-HAI group were(21.59±10.62)and(13.92±9.21)days,respectively,with statistical differences(all P＜0.05).Conclusion The occurrence of HAI in patients undergoing Da Vinci robotic thoracic surgery leads to direct economic losses,with obvious increases in expenses of nursing,laboratory diagnosis,western medicine(mainly an-timicrobial agents).Length of hospital stay of patients also prolongs.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.