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 explore the causal relationship between breast cancer and free fatty acid receptor 4(FFAR4)by using two-sample Mendelian randomization.Methods By using Genome-wide Association Studies and expression quantitative trait locus(eQTL)data,single nucleotide polymorphism sites closely related to breast cancer and FFAR4 were extracted.Causal effect values were calculated by using five methods:inverse variance weighting(IVW),MR-Egger,weighted median,simple mode and weighted mode.Cochran Q tests were used to detect heterogeneity,MR-Egger intercept tests and MR-PRESSO tests were used to assess level multiplicity,and the hold-out method was employed for sensitivity analysis to ensure robustness of the results.Additionally,Bayesian co-location analysis was used to evaluate whether FFAR4 expression shares the same causal genetic variant with breast cancer in given genomic region.Results A total of 12 eQTLs closely related to FFAR4 expression levels were included in this study.The results of IVW analysis showed that increased FFAR4 expression levels increased the risk of overall breast cancer,Luminal A,Luminal B/HER2-negative,and HER2-enhanced subtypes of breast cancer.The co-location analysis showed that the posterior probability of FFAR4 expression level and total breast cancer shared causal variation was 0.889.Conclusion There may be a causal relationship between FFAR4 expression and breast cancer.

Objective:To explore the correlation between bile acid profiles and early efficacy of biologics for Crohn's disease (CD) .Methods:Patients with active CD who were treated with induction therapy with biologics (ustekinumab, vedolizumab, or combination therapy) in outpatient and inpatient clinics from January 2021 to March 2024 in Jinhua Central Hospital were included. Clinical data and serum bile acid profile of patients before treatment were collected. At the end of induction therapy, CD patients were categorized into remission and non-remission groups based on the CD activity index (CDAI) scores. Compare the clinical data of the two groups of patients with CD before induction treatment with biological agents, retrospective analysis of bile acid profiles in relation to early efficacy of biologics.Results:A total of 100 patients with CD were included, including 74 patients in remission group and 26 patients in non-remission group. Univariate analysis showed that hemoglobin [137 (119, 147) g/L vs. 121 (109, 136) g/L, P = 0.027], erythrocyte pressure volume [ (0.40 ± 0.06) % vs. (0.38 ± 0.05) %, P = 0.030], total bile acids[3.8 (2.4, 6.1) μmol/L比2.0 (1.5, 2.7) μmol/L, P < 0.001], cholic acid [0.188 (0.059, 0.597) μmol/L vs. 0.055 (0.024, 0.111) μmol/L, P < 0.001], chenodeoxycholic acid [0.812 (0.268, 1.717) μmol/L vs. 0.308 (0.087, 0.552) μmol/L, P < 0.001], and deoxycholic acid [0.042 (0.001, 0.299) μmol/L vs. 0.002 (0.001, 0.159) μmol/L, P = 0.028] were signficantly higher in remission group than those in unremission group. In addition, the pretreatment endoscopic score (SES-CD) [4.0 (0, 6.0) vs. 6.0 (3.0, 10.5), P = 0.025], erythrocyte sedimentation rate (ESR) [9.0 (2.8, 20.0) mm/1 h vs. 28.0 (12.8, 40.8) mm/1 h, P < 0.001] and C reactive protein (CRP) [0.6 (0.2, 6.7) mg/L vs. 9.1 (1.5, 23.9) mg/L, P < 0.001] in the remission group were lower than those in the non-remission group. Multirariate logistic regression analysis showed that chenodeoxycholic acid ( OR = 3.317, 95% CI: 1.270-12.437; P = 0.041) and ESR ( OR =0.979, 95% CI: 0.957-0.997; P = 0.034) were the independent influencing affecting the efficacy of biologics for the treatment of Crohn's disease in early stage. Conclusion:Chenodeoxycholic acid is an independent influencing factor of early efficacy of biologics for Crohn's disease.

Objective To investigate the characteristics and differences between two type 2 diabetic model mice,db/db and KK-Ay,as models of diabetic nephropathy(DN),and to verify them with irbesartan treatment.Methods A total of 102 db/db and 102 KK-Ay mice(12 weeks old)were screened based on the albumin-to-creatinine ratio(ACR)and 24-hour urinary total protein(UCFP),with 78 mice of each strain selected and divided into 6 groups.The db/db+irbesartan group and KK-Ay+irbesartan group were administered irbesartan(40 mg/kg),the db/db group and KK-Ay group received an equal volume of drinking water for experimental animals,and the db/db+test article A groups and KK-Ay+test article A groups were given different doses of test article A(only the result of mortality data in the test articles groups were presented in the study,while other result were not shown).Wild-type C57BL/6J(WTa/WTb group)served as the normal control and were given experimental animal drinking water.Daily clinical observations were made,body mass was measured weekly,and ACR and UCFP were monitored periodically.At the end of administration,the mice were dissected,and the brain,liver,lungs and kidneys were collected,and the organ coefficients(organ mass× 1000/body mass)were calculated.Blood was collected to measure serum total protein(TP),albumin(Alb),blood urea nitrogen(BUN),glucose(GLU),triglycerides(TG),and cholesterol(CHO).Kidney tissues were stained with HE,MASSON,and PAS to observe histopathological changes.Results Among the 78 KK-Ay mice,5 died over 8 weeks,while among the 78 db/db mice,21 died over 6 weeks.ACR increased with age in both the db/db and KK-Ay groups but decreased in the db/db+irbesartan and KK-Ay+irbesartan groups,though without statistical significance(P＞0.05).UCFP increased with age in the KK-Ay group but significantly decreased after irbesartan treatment(P＜0.05).Compared with the WT groups,the kidney coefficients in the db/db and KK-Ay groups showed no significant changes(P＞0.05),while the brain liver coefficients decreased significantly(P＜0.01)and the liver coefficients increased significantly(P＜0.01),but they did not change after irbesartan treatment(P＞0.05).Compared with the WT groups,GLU and TG levels were significantly increased in the db/db and KK-Ay groups(P＜0.01).Compared with the KK-Ay group,GLU and TG levels were significantly reduced in the KK-Ay+irbesartan group(P＜0.01).In the db/db and KK-Ay groups,kidney tissues showed thickening of the glomerular mesangial matrix and mesangial cell proliferation,which were alleviated after irbesartan treatment.Conclusions Both 12-week-old db/db and KK-Ay mice can serve as models for DN research.Compared with db/db mice,KK-Ay mice exhibited smaller individual differences in ACR,fewer animal deaths after urine collection,and significant improvements in GLU,TG and UCFP after irbesartan treatment.

Objective:To explore the correlation between bile acid profiles and early efficacy of biologics for Crohn's disease (CD) .Methods:Patients with active CD who were treated with induction therapy with biologics (ustekinumab, vedolizumab, or combination therapy) in outpatient and inpatient clinics from January 2021 to March 2024 in Jinhua Central Hospital were included. Clinical data and serum bile acid profile of patients before treatment were collected. At the end of induction therapy, CD patients were categorized into remission and non-remission groups based on the CD activity index (CDAI) scores. Compare the clinical data of the two groups of patients with CD before induction treatment with biological agents, retrospective analysis of bile acid profiles in relation to early efficacy of biologics.Results:A total of 100 patients with CD were included, including 74 patients in remission group and 26 patients in non-remission group. Univariate analysis showed that hemoglobin [137 (119, 147) g/L vs. 121 (109, 136) g/L, P = 0.027], erythrocyte pressure volume [ (0.40 ± 0.06) % vs. (0.38 ± 0.05) %, P = 0.030], total bile acids[3.8 (2.4, 6.1) μmol/L比2.0 (1.5, 2.7) μmol/L, P < 0.001], cholic acid [0.188 (0.059, 0.597) μmol/L vs. 0.055 (0.024, 0.111) μmol/L, P < 0.001], chenodeoxycholic acid [0.812 (0.268, 1.717) μmol/L vs. 0.308 (0.087, 0.552) μmol/L, P < 0.001], and deoxycholic acid [0.042 (0.001, 0.299) μmol/L vs. 0.002 (0.001, 0.159) μmol/L, P = 0.028] were signficantly higher in remission group than those in unremission group. In addition, the pretreatment endoscopic score (SES-CD) [4.0 (0, 6.0) vs. 6.0 (3.0, 10.5), P = 0.025], erythrocyte sedimentation rate (ESR) [9.0 (2.8, 20.0) mm/1 h vs. 28.0 (12.8, 40.8) mm/1 h, P < 0.001] and C reactive protein (CRP) [0.6 (0.2, 6.7) mg/L vs. 9.1 (1.5, 23.9) mg/L, P < 0.001] in the remission group were lower than those in the non-remission group. Multirariate logistic regression analysis showed that chenodeoxycholic acid ( OR = 3.317, 95% CI: 1.270-12.437; P = 0.041) and ESR ( OR =0.979, 95% CI: 0.957-0.997; P = 0.034) were the independent influencing affecting the efficacy of biologics for the treatment of Crohn's disease in early stage. Conclusion:Chenodeoxycholic acid is an independent influencing factor of early efficacy of biologics for Crohn's disease.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

Objective To analyze the risk factors and clinical outcomes of cognitive impairment in elderly patients with heart disease after surgery.Methods A total of 156 patients with heart valve diseases undergoing coronary artery bypass surgery admitted to the First Affiliated Hospital of H ainan Medical University from October 2021 to December 2023 were prospectively recruited.At 7 d postoperatively,Montreal cognitive assessment(MoCA)scale was used to assess their cogni-tive function,and based on MoCA score＜26 or not,they patients were divided into a cognitive impairment group(n=61)and a control group(n=95).The clinical features were compared be-tween the two groups,and the risk factors for cognitive impairment were analyzed.All patients were followed up for 1 year to compare the outcomes of the two groups.Results The cognitive impairment group had significantly advanced age,larger proportions of concomitant chronic respiratory diseases and sarcopenia,increased ratio of undergoing open heart surgery,and elevated incidence of intraoperative hypotension than the control group(P＜0.05,P＜0.01).Multivariate logistic regression analysis indicated that age,chronic respiratory diseases,sarcopenia,open heart surgery,and intraoperative hypotension were independent risk factors for postoperative cognitive impairment in elderly patients with heart diseases(OR=1.081,95％CI:1.007-1.161,P=0.030;OR=2.538,95％CI:1.062-6.066,P=0.036;OR=2.650,95％CI:1.174-5.985,P=0.019;OR=3.104,95％CI:1.391-6.929,P=0.006;OR=3.478,95％CI:1.298-9.322,P=0.0013).There was no statistical difference in preoperative MoCA scores between the two groups(27.90±1.40 vs 28.20±1.40,P=0.195).The MoCA score at 7 d and 6 and 12 months after surgery were obviously lower in the cognitive impairment group than the control group(22.90±1.27 vs 27.73±1.08,P=0.000;24.72±1.66 vs 27.73±1.23,P=0.000;25.48±1.73 vs 27.62±1.22,P=0.000).Age was identified as an independent factor affecting the outcome of cognitive function in the patients(OR=1.168,95％CI:1.035-1.318).Conclusion The incidence of postoperative cog-nitive impairment is relatively high in elderly patients with heart disease.So,relevant risk factors should be addressed to strengthen the prevention and management.

Objective:To evaluate the efficacy and safety of upadacitinib in the real-world treatment of difficult-to-treat Crohn's disease (DTT-CD) .Methods:This multicenter, retrospective cohort study included patients diagnosed with DTT-CD according to the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) criteria, and treated at eight Chinese inflammatory bowel disease centers between January 2023 and March 2025. Clinical outcomes were assessed after 12 weeks of induction therapy with upadacitinib (45 mg qd), including clinical remission rate, clinical response rate, and incidence of adverse events.Results:Among 151 enrolled DTT-CD patients, the clinical remission rate was 47.0%, and the clinical response rate was 90.7% after 12 weeks of treatment. Adverse events occurred in 42 cases (27.8%) .Conclusion:Upadacitinib demonstrated favorable efficacy in inducing clinical remission in DTT-CD patients, with a good safety profile at the induction dose (45 mg qd) .

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 investigate the characteristics and differences between two type 2 diabetic model mice,db/db and KK-Ay,as models of diabetic nephropathy(DN),and to verify them with irbesartan treatment.Methods A total of 102 db/db and 102 KK-Ay mice(12 weeks old)were screened based on the albumin-to-creatinine ratio(ACR)and 24-hour urinary total protein(UCFP),with 78 mice of each strain selected and divided into 6 groups.The db/db+irbesartan group and KK-Ay+irbesartan group were administered irbesartan(40 mg/kg),the db/db group and KK-Ay group received an equal volume of drinking water for experimental animals,and the db/db+test article A groups and KK-Ay+test article A groups were given different doses of test article A(only the result of mortality data in the test articles groups were presented in the study,while other result were not shown).Wild-type C57BL/6J(WTa/WTb group)served as the normal control and were given experimental animal drinking water.Daily clinical observations were made,body mass was measured weekly,and ACR and UCFP were monitored periodically.At the end of administration,the mice were dissected,and the brain,liver,lungs and kidneys were collected,and the organ coefficients(organ mass× 1000/body mass)were calculated.Blood was collected to measure serum total protein(TP),albumin(Alb),blood urea nitrogen(BUN),glucose(GLU),triglycerides(TG),and cholesterol(CHO).Kidney tissues were stained with HE,MASSON,and PAS to observe histopathological changes.Results Among the 78 KK-Ay mice,5 died over 8 weeks,while among the 78 db/db mice,21 died over 6 weeks.ACR increased with age in both the db/db and KK-Ay groups but decreased in the db/db+irbesartan and KK-Ay+irbesartan groups,though without statistical significance(P＞0.05).UCFP increased with age in the KK-Ay group but significantly decreased after irbesartan treatment(P＜0.05).Compared with the WT groups,the kidney coefficients in the db/db and KK-Ay groups showed no significant changes(P＞0.05),while the brain liver coefficients decreased significantly(P＜0.01)and the liver coefficients increased significantly(P＜0.01),but they did not change after irbesartan treatment(P＞0.05).Compared with the WT groups,GLU and TG levels were significantly increased in the db/db and KK-Ay groups(P＜0.01).Compared with the KK-Ay group,GLU and TG levels were significantly reduced in the KK-Ay+irbesartan group(P＜0.01).In the db/db and KK-Ay groups,kidney tissues showed thickening of the glomerular mesangial matrix and mesangial cell proliferation,which were alleviated after irbesartan treatment.Conclusions Both 12-week-old db/db and KK-Ay mice can serve as models for DN research.Compared with db/db mice,KK-Ay mice exhibited smaller individual differences in ACR,fewer animal deaths after urine collection,and significant improvements in GLU,TG and UCFP after irbesartan treatment.